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Li Y, Zhou T, Liu Y, Qi J, Zhang L, Gu R, Sun D, Wang X. Low-Dose Rivaroxaban vs. Aspirin in Addition to Clopidogrel After Percutaneous Coronary Intervention in Coronary Atherosclerotic Heart Disease Patients with Gastrointestinal Disease. Cardiovasc Drugs Ther 2025:10.1007/s10557-025-07682-5. [PMID: 40116999 DOI: 10.1007/s10557-025-07682-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2025] [Indexed: 03/23/2025]
Abstract
PURPOSE Dual antiplatelet therapy (DAPT) is the cornerstone for patients with coronary atherosclerotic heart disease (CHD) undergoing percutaneous coronary intervention (PCI) while increasing the risk of bleeding, particularly when combined with gastrointestinal disease (GID). Rivaroxaban 10 mg once daily is widely used in Asia. This study compared the effects of low-dose rivaroxaban (10 mg daily) plus clopidogrel vs. DAPT in CHD patients with GID undergoing PCI. METHODS In this prospective, single-center, randomized controlled trial, eligible CHD patients with GID undergoing PCI were randomized (1:1) to either the dual pathway inhibition (DPI) group (rivaroxaban 10 mg plus clopidogrel 75 mg daily) or the DAPT group (aspirin 100 mg plus clopidogrel 75 mg daily). The primary outcome was Bleeding Academic Research Consortium (BARC) type 2-5 bleeding. The secondary outcome was major adverse cardiovascular or cerebrovascular events (MACCE), which included cardiac death, nonfatal myocardial infarction, ischemia-driven target vessel revascularization, all-cause death, stent thrombosis, and stroke during the 6-month follow-up. RESULTS A total of 1042 patients were enrolled and analyzed (DPI, 522; DAPT, 520). Low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT in BARC type 2-5 bleeding [8 (1.5%) vs. 6 (1.2%), absolute risk difference 0.38%, 95% confidence interval (CI) (- 1.02-1.78), p < 0.0001 for non-inferiority]. Abdominal pain was significantly lower in the DPI group (p = 0.009). Other abdominal discomforts, gastrointestinal bleeding, or MACCE were similar. CONCLUSIONS In CHD patients with GID undergoing PCI, low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2100044319. Registered on March 16, 2021.
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Affiliation(s)
- Yue Li
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China
- College of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Tienan Zhou
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China
| | - Yan Liu
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China
- College of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Junxian Qi
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China
| | - Lei Zhang
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China
| | - Ruoxi Gu
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China
| | - Dongyuan Sun
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China
| | - Xiaozeng Wang
- National Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China.
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Ren J, Wang N, Zhang X, Song F, Zheng X, Han X. A systematic review and meta-analysis of the morbidity of efficacy endpoints and bleeding events in elderly and young patients treated with the same dose rivaroxaban. Ann Hematol 2024; 103:4363-4373. [PMID: 38710878 DOI: 10.1007/s00277-024-05767-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 04/17/2024] [Indexed: 05/08/2024]
Abstract
Rivaroxaban is a new direct oral anticoagulant, and the same dose is recommended for older and young patients. However, recent real-world studies show that older patients may need dose adjustment to prevent major bleeding. At present, the evidence for dose adjustment in older patients is extremely limited with only a few reports on older atrial fibrillation patients. The aim of this study was to review the morbidity data of adverse events and bleeding events across all indications for older and young patients treated with the same dose of rivaroxaban to provide some support for dosage adjustment in older patients. The PubMed, EMBASE, ClinicalTrials, Cochrane and Web of Science databases were searched for randomized controlled trials (RCTs) published between January 1, 2005, and October 10, 2023. The primary outcomes were the morbidity of bleeding events and efficacy-related adverse events. Summary estimates were calculated using a random effects model. Eighteen RCTs were included in the qualitative analysis. The overall morbidity of primary efficacy endpoints was higher in older patients compared to the young patients (3.37% vs. 2.60%, χ2 = 5.24, p = 0.022). Similarly, a higher morbidity of bleeding was observed in older patients compared to the young patients (4.42% vs. 6.03%, χ2 = 13.22, p < 0.001). Among all indications, deep vein thrombosis, pulmonary embolism and atrial fibrillation were associated with the highest incidence of bleeding in older patients, suggesting that these patients may be most need dose adjustment. Patients older than 75 years may require extra attention to prevent bleeding. The same dose of rivaroxaban resulted in higher bleeding morbidity and morbidity of efficacy-related adverse events in older patients compared to the young patients. An individualized dose adjustment may be preferred for older patients rather than a fixed dose that fits all.
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Affiliation(s)
- Jianwei Ren
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Na Wang
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Xuan Zhang
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Fuyu Song
- Center for Food and Drug Inspection, National Medical Products Administration, Beijing, 100053, China
- NHC Key Laboratory of Mental Health, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Peking University Institute of Mental Health, Peking University, Beijing, 100191, China
| | - Xin Zheng
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Xiaohong Han
- Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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Hussen M, Woubshet K, Bacha S, Ketema W. Simple Criteria, Yet the Dearth Utilization-Antithrombotic Management Practice among Atrial Fibrillation Patients at Hawassa University Comprehensive Specialized Hospital, Hawassa, Sidama, Ethiopia. Cardiol Res Pract 2024; 2024:6665787. [PMID: 38835499 PMCID: PMC11150045 DOI: 10.1155/2024/6665787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 01/05/2024] [Accepted: 05/22/2024] [Indexed: 06/06/2024] Open
Abstract
Background Atrial fibrillation (AF) is associated with significant mortality and morbidity from stroke and thromboembolism. Despite the availability of effective oral anticoagulation medication, AF patients remain at a high risk of stroke if not treated properly. The purpose of this study was to evaluate antithrombotic therapy practices in patients with AF in the adult cardiac clinic at Hawassa University Comprehensive Specialized Hospital (HUCSH). Methods It was a retrospective document review study. Total charts of 119 patients who had follow-up at the adult cardiac clinic with a history of documented AF from January 1 to December 30, 2018, were included. Indicators for antithrombotic therapy based on the congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74, and sex category (female) (CHA2DS2-VASc) score were recorded. A p value of 0.05 was considered statistically significant. Data analysis was done using SPSS 23 software. Results In this study, about 55% of patients with AF were receiving the appropriate antithrombotic treatment. The patients were 48 ± 18.2 years old. Of these, 70% were women. The most frequent underlying cardiac etiology was chronic rheumatic valvular heart disease (50%), followed by cardiomyopathy (14%). In nonvalvular AF, the mean CHA2DS2VASc score was 4.0 ± 1.07. In valvular AF compared to nonvalvular AF, the need for appropriate antithrombotic therapy was substantially greater (p 0.0001). Only 8 (13.6%) of the warfarin-using patients had adequate anticoagulation. Conclusion The study's findings in regard to antithrombotic usage and maintenance of appropriate antithrombotics for stroke prevention in our patients revealed a discrepancy between recommendations and practice. Therefore, we demand that patients with AF who meet the criteria utilize antithrombotics properly to prevent stroke. Warfarin-taking patients' subpar optimum anticoagulation has to be addressed. Lastly, we advocate proper CHA2DS2-VASc score utilization for nonvalvular heart disease. A regular INR follow-up is also advised for patients who have started taking warfarin.
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Affiliation(s)
- Mubarak Hussen
- Department of Internal Medicine, College of Medicine and Health Sciences, School of Medicine, P.O. Box 1560, Hawassa, Ethiopia
- New York Internal Medicine Specialty Clinic, Hawassa, Ethiopia
| | - Kindie Woubshet
- Department of Internal Medicine, College of Medicine and Health Sciences, School of Medicine, P.O. Box 1560, Hawassa, Ethiopia
- Panacea Primary Hospital, Hawassa, Ethiopia
| | - Seifu Bacha
- Department of Internal Medicine, Saint Paul Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Worku Ketema
- Department of Pediatrics, College of Medicine and Health Sciences, School of Medicine, P.O. Box 1560, Hawassa, Ethiopia
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Alkhezi OS, Buckley LF, Fanikos J. Trends in Oral Anticoagulant Use and Individual Expenditures Across the United States from 2014 to 2020. Am J Cardiovasc Drugs 2024; 24:433-444. [PMID: 38583107 PMCID: PMC11324351 DOI: 10.1007/s40256-024-00638-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/10/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND Landmark clinical trials have expended the indications for the direct oral anticoagulants (DOACs), but contemporary data on usage and expenditure patterns are lacking. OBJECTIVE This study aimed to assess annual trends in oral anticoagulant (OAC) utilization and expenditure across the United States (US) from 2014 to 2020. METHODS We utilized the Medical Expenditure Panel Survey (MEPS) to study the trends of use and expenditures of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban between 2014 and 2020 in the US. Survey respondents reported OAC use within the past year, which was verified against pharmacy records. Payment information was obtained from the respondent's pharmacy and was categorized as third-party or self/out-of-pocket. Potential indications and medical conditions of interest for OAC therapy were identified from respondent-reported medical conditions. We estimated the national number of OAC users and total expenditures across age, sex, race, ethnicity, insurance, and medical condition subgroups. Trends of OAC users' characteristics, expenditure, and number of prescriptions were evaluated using the Mann-Kendall test for trends. RESULTS Between 2014 and 2020, the number of warfarin users decreased from 3.8 million (70% of all OAC users) to 2.2 million (p = 0.007) [29% of all OAC users], while the number of DOAC users increased from 1.6 million (30% of all OAC users) to 5.4 million (p = 0.003) [70% of all OAC users]. The total expenditure of OACs in the US increased from $3.4 billion in 2014 to $17.8 billion in 2020 (p = 0.003), which was driven by the increase in DOAC expenditures (p = 0.003). CONCLUSIONS DOACs have replaced warfarin as the preferred OAC in the US. The increased costs associated with DOAC use may decline when generic formulations are approved.
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Affiliation(s)
- Omar S Alkhezi
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia.
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA, USA.
| | - Leo F Buckley
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA, USA
| | - John Fanikos
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA, USA
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Lilja J, Själander A, Själander S. Prevalence of atrial fibrillation and reasons for undertreatment with oral anticoagulants. J Thromb Thrombolysis 2024; 57:101-106. [PMID: 37704908 PMCID: PMC10830806 DOI: 10.1007/s11239-023-02890-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/24/2023] [Indexed: 09/15/2023]
Abstract
OBJECTIVES To investigate the prevalence of atrial fibrillation (AF), the proportion of AF patients not receiving oral anticoagulation (OAC) and reasons for abstaining from OAC treatment. METHODS A retrospective cross-sectional study of patients aged 18 years or older with an AF diagnosis on June 1st 2020 in Västernorrland County, Sweden. AF diagnosis was retrieved using the ICD10 code I.48, and medical records were reviewed for comorbidities and documented reasons to abstain OAC treatment. RESULTS Of 197 274 residents in Västernorrland County, 4.7% (9 304/197 274) had a documented AF diagnosis. Of these, 19% (1 768/9 304) had no OAC treatment, including 4.2% (393/9 304) with no indication, 2.5% (233/9 304) with a questionable and 2.5% (231/9 304) with a documented clear contraindication for OAC. In total 9.8% (911/9 304) were not treated with OAC despite indication and no reasonable documented contraindication, thus 90.8% (8 447/9 304) of all AF-patients were eligible for OAC treatment. Common reasons for abstaining treatment without reasonable contraindication were present sinus rhythm in 13.7% (125/911), perceived not an OAC candidate in 10.6% (97/911) and anemia in the past in 4.3% (39/911). CONCLUSIONS In the population of Västernorrland County, a very high AF prevalence of 4.7% was found, of which just over 90% would theoretically benefit from OAC treatment. This is higher than previously reported and stresses the importance of stroke prevention in this large patient group.
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Affiliation(s)
- Johan Lilja
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Anders Själander
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Sara Själander
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
- Department of Cardiology, Sundsvall Hospital, 856 43, Sundsvall, Sweden.
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Pan MM, Zhang C, Shen L, Sha JJ, Shen H, Yan YD, Wang J, Wang X, Lin HW, Gu ZC. A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial. Trials 2023; 24:623. [PMID: 37779187 PMCID: PMC10544439 DOI: 10.1186/s13063-023-07667-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 09/21/2023] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF. METHODS The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction. DISCUSSION This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries. TRIAL REGISTRATION ChiCTR ChiCTR2200062123. Registered on 23 July 2022.
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Affiliation(s)
- Mang-Mang Pan
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Chi Zhang
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
- School of Medicine, Tongji University, Shanghai, 200092, China
| | - Long Shen
- Department of Cardiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Jing-Jing Sha
- Shanghai Pudong New Area, Jinyang Community Health Service Center, Shanghai, 200136, China
| | - Hui Shen
- Shanghai Pudong New Area, Huamu Community Health Service Center, Shanghai, 201204, China
| | - Yi-Dan Yan
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Jia Wang
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Xin Wang
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Hou-Wen Lin
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Zhi-Chun Gu
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
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Xia Y, Hu Y, Tang L. Factor XIa Inhibitors as a Novel Anticoagulation Target: Recent Clinical Research Advances. Pharmaceuticals (Basel) 2023; 16:866. [PMID: 37375813 DOI: 10.3390/ph16060866] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/03/2023] [Accepted: 06/04/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND While current clinically administered anticoagulant medications have demonstrated effectiveness, they have also precipitated significant risks: severe bleeding complications including, but not limited to, gastrointestinal hemorrhaging and intracranial and other life-threatening major bleedings. An ongoing effort is being made to identify the best targets for anticoagulant-targeted drugs. Coagulation factor XIa (FXIa) is emerging as an important target of current anticoagulant treatment. OBJECTIVE This review will summarize the development of anticoagulants and recent advances in clinical trials of experimental factor XI inhibitors from a clinical application perspective. RESULTS As of 1 January 2023, our search screening included 33 clinical trials. We summarized the research progress of FXIa inhibitors from seven clinical trials that evaluated their efficacy and safety. The results showed no statistically meaningful distinction in the primary efficacy between patients receiving FXIa inhibitors compared to controls (RR = 0.796; 95% CI: 0.606-1.046; I2 = 68%). The outcomes did not indicate a statistical difference in the occurrence of any bleeding between patients receiving FXIa inhibitors compared to controls (RR = 0.717; 95% CI: 0.502-1.023; I2 = 60%). A subgroup analysis found significant differences in severe bleeding and clinically relevant hemorrhaging in subjects receiving FXIa inhibitors compared to Enoxaparin (RR = 0.457; 95% CI: 0.256-0.816; I2 = 0%). CONCLUSIONS Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants.
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Affiliation(s)
- Yunqing Xia
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China
| | - Yu Hu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China
- Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Liang Tang
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China
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Santostasi G, Denas G, Pengo V. New pharmacotherapeutic options for oral anticoagulant treatment in atrial fibrillation patients aged 65 and older: factor XIa inhibitors and beyond. Expert Opin Pharmacother 2023; 24:1335-1347. [PMID: 37243619 DOI: 10.1080/14656566.2023.2219391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 05/29/2023]
Abstract
INTRODUCTION Although much progress has been made using anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation, bleeding is still a major concern. AREAS COVERED This article reviews current pharmacotherapeutic options in this setting. Particular emphasis is placed on the ability of the new molecules to minimize the bleeding risk in elderly patients. A systematic search of PubMed, Web of Science, and the Cochrane Library up to March 2023 was carried out. EXPERT OPINION Contact phase of coagulation is a possible new target for anticoagulant therapy. Indeed, congenital or acquired deficiency of contact phase factors is associated with reduced thrombotic burden and limited risk of spontaneous bleeding. These new drugs seem particularly suitable for stroke prevention in elderly patients with non-valvular atrial fibrillation in whom the hemorrhagic risk is high. Most of anti Factor XI (FXI) drugs are for parenteral use only. A group of small molecules are for oral use and therefore are candidates to substitute direct oral anticoagulants (DOACs) for stroke prevention in elderly patients with atrial fibrillation. Doubts remain on the possibility of impaired hemostasis. Indeed, a fine calibration of inhibition of contact phase factors is crucial for an effective and safe treatment.
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Affiliation(s)
| | - Gentian Denas
- Cardiology Clinic, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
| | - Vittorio Pengo
- Cardiology Clinic, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy
- Arianna Foundation on Anticoagulation, Bologna, Italy
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Bleckwenn M, Schumacher N, Puth MT, Just JM, Weckbecker K. [Changes in Prescription Patterns of Oral Anticoagulants in Family Practices after Marketing Approval of Direct Oral Anticoagulants]. DAS GESUNDHEITSWESEN 2023; 85:193-198. [PMID: 35426089 PMCID: PMC11248672 DOI: 10.1055/a-1778-3831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
AIM OF THE STUDY Since 2011, non-vitamin-K-dependent oral anticoagulants (NOAC) have extended the spectrum of anticoagulation therapy. Initially, the approval of NOAC was limited to the prophylaxis of postoperative thrombosis, but in the course of time the spectrum was extended to the therapy of thrombosis and embolism as well as anticoagulation in non-valvular atrial fibrillation. The study was designed to examine how the approval of NOAC had affected the prescribing behaviour of general practitioners in the first years of their approval. METHODS In a retrospective longitudinal study, the prescriptions of anticoagulants between 2012 and 2017 were analysed in 3 general practitioners' practices in the Bonn area. The study included all patients for whom at least one prescription from a NOAC or a vitamin K antagonist (VKA) was documented in the administrative system of the practices during this period. RESULTS A total of n=579 patient files were evaluated (47% female; median age 75 years). Of these, 47% received a VKA, and 40% a NOAC (59% rivaroxaban, 29% apixaban, 9% dabigatran and 3% edoxaban). During the period under examination, the share of VKA prescriptions decreased from 45% to 14% and the share of NOAC increased from 28% to 87%. Anti-coagulation was changed in 12%. The most frequent change was from a VKA to a NOAC (70%). CONCLUSION After marketing approval, the use of NOAC in the initial prescriptions increased steadily. This trend can also be seen in other European studies. VKA are mainly prescribed to patients with stable oral anticoagulation. As recommended in the guidelines, anticoagulation is changed mainly when problems occur during therapy. If the trend in the prescription of anticoagulants continues, in the medium term, VKA will only be prescribed for patients who have been stable for many years and for patients with artificial heart valves.
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Affiliation(s)
- Markus Bleckwenn
- Selbstständige Abteilung für Allgemeinmedizin,
Medizinische Fakultät, Universität Leipzig, Germany
| | - Nadine Schumacher
- Institut für Allgemeinmedizin und Interprofessionelle
Versorgung, Universität Witten/Herdecke Department für
Humanmedizin, Witten, Germany
| | - Marie-Therese Puth
- Institut für Medizinische Biometrie, Informatik und
Epidemiologie (IMBIE), Universitätsklinikum Bonn, Bonn, Germany
| | - Johannes Maximilian Just
- Institut für Allgemeinmedizin und Interprofessionelle
Versorgung, Universität Witten/Herdecke Department für
Humanmedizin, Witten, Germany
| | - Klaus Weckbecker
- Institut für Allgemeinmedizin und Interprofessionelle
Versorgung, Universität Witten/Herdecke Department für
Humanmedizin, Witten, Germany
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Al-Horani RA, Afosah DK, Mottamal M. Triazol-1-yl Benzamides Promote Anticoagulant Activity via Inhibition of Factor XIIa. Cardiovasc Hematol Agents Med Chem 2023; 21:108-119. [PMID: 36321236 PMCID: PMC10249145 DOI: 10.2174/1871525721666221031141323] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 09/13/2022] [Accepted: 10/03/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND Human factor XIIa (FXIIa) is a plasma serine protease that plays a significant role in several physiological and pathological processes. Animal models have revealed an important contribution of FXIIa to thromboembolic diseases. Remarkably, animals and patients with FXII deficiency appear to have normal hemostasis. Thus, FXIIa inhibition may serve as a promising therapeutic strategy to attain safer and more effective anticoagulation. Very few small molecule inhibitors of FXIIa have been reported. We synthesized and investigated a focused library of triazol-1-yl benzamide derivatives for FXIIa inhibition. METHODS We chemically synthesized, characterized, and investigated a focused library of triazol- 1-yl benzamide derivatives for FXIIa inhibition. Using a standardized chromogenic substrate hydrolysis assay, the derivatives were evaluated for inhibiting human FXIIa. Their selectivity over other clotting factors was also evaluated using the corresponding substrate hydrolysis assays. The best inhibitor affinity to FXIIa was also determined using fluorescence spectroscopy. Effects on the clotting times (prothrombin time (PT) and activated partial thromboplastin time (APTT)) of human plasma were also studied. RESULTS We identified a specific derivative (1) as the most potent inhibitor in this series. The inhibitor exhibited nanomolar binding affinity to FXIIa. It also exhibited significant selectivity against several serine proteases. It also selectively doubled the activated partial thromboplastin time of human plasma. CONCLUSION Overall, this work puts forward inhibitor 1 as a potent and selective inhibitor of FXIIa for further development as an anticoagulant.
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Affiliation(s)
- Rami A. Al-Horani
- Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
| | - Daniel K. Afosah
- Department of Chemistry and Biochemistry, Washington and Lee University, Lexington VA 24450, USA
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Badimon JJ, Escolar G, Zafar MU. Factor XI/XIa Inhibition: The Arsenal in Development for a New Therapeutic Target in Cardio- and Cerebrovascular Disease. J Cardiovasc Dev Dis 2022; 9:437. [PMID: 36547434 PMCID: PMC9781521 DOI: 10.3390/jcdd9120437] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/25/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022] Open
Abstract
Despite major advancements in the development of safer and more effective anticoagulant agents, bleeding complications remain a significant concern in the treatment of thromboembolic diseases. Improvements in our understanding of the coagulation pathways highlights the notion that the contact pathway-specifically factor XI (FXI)-has a greater role in the etiopathogenesis of thrombosis than in physiological hemostasis. As a result, a number of drugs targeting FXI are currently in different stages of testing and development. This article aims to review the different strategies directed towards FXI-inhibition with a brief summation of the agents in clinical development, and to comment on the therapeutic areas that could be explored for potential indications. Therapeutics targeting FXI/FXIa inhibition have the potential to usher in a new era of anticoagulation therapy.
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Affiliation(s)
- Juan J. Badimon
- Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Gines Escolar
- Department of Hematopathology, Hospital Clinic, 08036 Barcelona, Spain
| | - M. Urooj Zafar
- Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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12
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Abrignani MG, Lombardo A, Braschi A, Renda N, Abrignani V, Lombardo RM. Time trends in antithrombotic therapy prescription patterns: Real-world monocentric study in hospitalized patients with atrial fibrillation. World J Cardiol 2022; 14:576-598. [PMID: 36483763 PMCID: PMC9724000 DOI: 10.4330/wjc.v14.i11.576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 07/04/2022] [Accepted: 10/27/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) were upgraded from an IIAa recommendation in 2012 to an IA in 2016. In real-world scenarios, however, OAC prescription is still suboptimal, mainly for DOACs. AIM To evaluate OAT temporal prescription patterns in a cohort of patients hospitalized with AF in a Cardiology Department. METHODS A retrospective observational study was conducted on a cohort of hospitalized patients in a secondary setting (Trapani, Italy) from 2010 to 2021 with AF as the main or secondary diagnosis. For 4089 consecutive patients, the variables extracted from the Cardiology department database were: Sex, age, time of hospitalization, antithrombotic therapy (warfarin, acenocoumarol, apixaban, dabigatran, edoxaban, rivaroxaban, aspirin, clopidogrel, other antiplatelet agents, low molecular weight heparin, and fondaparinux), diagnosis at discharge and used resources. Basal features are presented as percentage values for categorized variables and as mean +/- SD for categorized once. RESULTS From January 1st, 2010 to October 6th, 2021, 25132 patients were hospitalized in our department; 4089 (16.27%, mean age 75.59+/-10.82) were discharged with AF diagnosis; of them, 2245 were males (54.81%, mean age 73.56+/-11.45) and 1851 females (45.19%, mean age 78.06+/-9.47). Average length of stay was 5.76+/-4.88 days; 154 patients died and 88 were moved to other Departments/Structures. AF was the main diagnosis in 899 patients (21.94%). The most frequent main diagnosis in patients with AF was acute myocardial infarction (1973 discharges, 48.19%). The most frequent secondary cardiac diagnosis was chronic coronary syndrome (1864 discharges, 45.51%), and the most frequent secondary associated condition was arterial hypertension (1010 discharges, 24.66%). For the analysis of antithrombotic treatments, the final sample included 3067 patients, after excluding in-hospital deaths, transferred out or self-discharged patients, as well as discharges lacking indications for prescribed treatments. OAC treatment increased significantly (35.63% in 2010-2012 vs 61.18% in 2019-2021, +25.55%, P < 0.0001), in spite of any antiplatelet agent use. This rise was due to increasing use of DOACs, with or without antiplatelet agents, from 3.04% in 2013-2015 to 50.06% in 2019-2021 (+47.02%, P < 0.0001) and was greater for factor Xa inhibitors, especially apixaban. In addition, treatment with a vitamin K antagonist, in spite of any antiplatelet agent use, decreased from 35.63% in 2010-2012 to 11.12% in 2019-2021 (-24.48%, P < 0.0001), as well as any antiplatelet therapy, alone or in double combination, (49.18% in 2010-2012 vs 34.18% in 2019-2021, -15.00%, P < 0.0001); and patients not receiving antithrombotic therapy declined with time (14.58% in 2010-2012 vs 1.97% in 2021, P < 0.0001). CONCLUSION Real-world patients with AF are elderly and affected by cardiovascular and non-cardiovascular diseases. The percentage of patients on OAT and DOACs increased. These data suggest a slow, gradual guidelines implementation process.
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Affiliation(s)
- Maurizio Giuseppe Abrignani
- Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, ASP Trapani, Trapani 91100, Trapani, Italy.
| | - Alberto Lombardo
- Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, ASP Trapani, Trapani 91100, Trapani, Italy
| | - Annabella Braschi
- Department of Psychology, Educational Science and Human Movement, University of Palermo, Palermo 90100, Palermo, Italy
| | - Nicolò Renda
- Department of Medicine and Surgery, University of Parma, Parma 43100, Parma, Italy
| | - Vincenzo Abrignani
- Operative Unit of Internal Medicine with Stroke Care, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE) "G. D'Alessandro", University of Palermo, Palermo 90100, Palermo, Italy
| | - Renzo M Lombardo
- Department of Cardiology, Operative Unit of Cardiology, Department of Medicine, S. Antonio Abate Hospital of Trapani, Trapani 91100, Trapani, Italy
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13
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Oral anticoagulants: a systematic overview of reviews on efficacy and safety, genotyping, self-monitoring, and stakeholder experiences. Syst Rev 2022; 11:232. [PMID: 36303235 PMCID: PMC9615370 DOI: 10.1186/s13643-022-02098-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/08/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND This systematic overview was commissioned by England's Department of Health and Social Care (DHSC) to assess the evidence on direct (previously 'novel') oral anticoagulants (OACs), compared with usual care, in adults, to prevent stroke related to atrial fibrillation (AF), and to prevent and treat venous thromboembolism (VTE). Specifically, to assess efficacy and safety, genotyping, self-monitoring, and patient and clinician experiences of OACs. METHODS We searched MEDLINE, Embase, ASSIA, and CINAHL, in October, 2017, updated in November 2021. We included systematic reviews, published from 2014, in English, assessing OACs, in adults. We rated review quality using AMSTAR2 or the JBI checklist. Two reviewers extracted and synthesised the main findings from the included reviews. RESULTS We included 49 systematic reviews; one evaluated efficacy, safety, and cost-effectiveness, 17 assessed genotyping, 23 self-monitoring or adherence, and 15 experiences (seven assessed two topics). Generally, the direct OACs, particularly apixaban (5 mg twice daily), were more effective and safer than warfarin in preventing AF-related stroke. For VTE, there was little evidence of differences in efficacy between direct OACs and low-molecular-weight heparin (prevention), warfarin (treatment), and warfarin or aspirin (secondary prevention). The evidence suggested that some direct OACs may reduce the risk of bleeding, compared with warfarin. One review of genotype-guided warfarin dosing assessed AF patients; no significant differences in stroke prevention were reported. Education about OACs, in patients with AF, could improve adherence. Pharmacist management of coagulation may be better than primary care management. Patients were more adherent to direct OACs than warfarin. Drug efficacy was highly valued by patients and most clinicians, followed by safety. No other factors consistently affected patients' choice of anticoagulant and adherence to treatment. Patients were more satisfied with direct OACs than warfarin. CONCLUSIONS For stroke prevention in AF, direct OACs seem to be more effective and safer than usual care, and apixaban (5 mg twice daily) had the best profile. For VTE, there was no strong evidence that direct OACs were better than usual care. Education and pharmacist management could improve coagulation control. Both clinicians and patients rated efficacy and safety as the most important factors in managing AF and VTE. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017084263-one deviation; efficacy and safety were from one review.
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14
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Khatib R, Glowacki N, Byrne J, Brady P. Impact of social determinants of health on anticoagulant use among patients with atrial fibrillation: Systemic review and meta-analysis. Medicine (Baltimore) 2022; 101:e29997. [PMID: 36107589 PMCID: PMC9439798 DOI: 10.1097/md.0000000000029997] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND A growing body of literature now exists examining associations between social determinants of health (SDOH) and adverse outcomes in patients with atrial fibrillation; however, little is available on anticoagulant prescriptions and the impact of SDOH. PURPOSE Evaluate the impact of SDOH on anticoagulant prescriptions in patients with atrial fibrillation. DATA SOURCES Medline and Embase databases up to January 2021. STUDY SELECTION Noninterventional studies were included if they reported associations between at least 1 of 14 SDOH domains and anticoagulant prescription in patients with atrial fibrillation. Two investigators independently screened and collected data. DATA EXTRACTION Two investigators independently screened and collected data. DATA SYNTHESIS Meta-analyses using random-effect models evaluated associations between SDOH and receiving an anticoagulant prescription. We included 13 studies, 11 of which were included in meta-analyses that reported on the impact of 9 of the 14 SDOH included in the search. Pooled estimates indicate a 0.85 (95% confidence interval [CI]: 0.75, 0.97) lower odds of receiving anticoagulant prescriptions among Black compared to non-Black patients (reported in 6 studies); 0.42 (95% CI: 0.32, 0.55) lower odds of receiving anticoagulant prescriptions among patients with mental illness compared to those without mental illness (2 studies); and a 0.64 (95% CI: 0.42, 0.96) lower likelihood of receiving oral anticoagulant prescription among employed patients compared to unemployed patients (2 studies). LIMITATIONS SDOH lack consistent definitions and measures within the electronic health record. CONCLUSION The literature reports on only half of the SDOH domains we searched for, indicating that many SDOH are not routinely assessed. Second, social needs impact the decision to prescribe anticoagulants, confirming the need to screen for and address social needs in the clinical setting to support clinicians in providing guideline concordant care to their patients. REGISTRATION This systematic review and meta-analysis was registered with PROSPERO.
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Affiliation(s)
- Rasha Khatib
- Advocate Aurora Research Institute, Advocate Aurora Health, Downers Grove, IL
- *Correspondence: Rasha Khatib, PhD, Advocate Aurora Research Institute, Advocate Aurora Health, 3075 Highland Parkway, Suite 600, Downers Grove, IL 60515, USA (e-mail: )
| | - Nicole Glowacki
- Advocate Aurora Research Institute, Advocate Aurora Health, Downers Grove, IL
| | - John Byrne
- School of Molecular & Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL
| | - Peter Brady
- Department of Cardiovascular Medicine, Advocate Illinois Masonic Medical Center, Chicago, IL
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15
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Xu G, Liu Z, Wang X, Lu T, DesJarlais RL, Thieu T, Zhang J, Devine ZH, Du F, Li Q, Milligan CM, Shaffer P, Cedervall PE, Spurlino JC, Stratton CF, Pietrak B, Szewczuk LM, Wong V, Steele RA, Bruinzeel W, Chintala M, Silva J, Gaul MD, Macielag MJ, Nargund R. Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions. J Med Chem 2022; 65:10419-10440. [PMID: 35862732 DOI: 10.1021/acs.jmedchem.2c00442] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent FXIa inhibitors with good oral bioavailability has been challenging. Herein, we describe our discovery effort, utilizing nonclassical interactions to improve potency, cellular permeability, and oral bioavailability by enhancing the binding while reducing polar atoms. Beginning with literature-inspired pyridine N-oxide-based FXIa inhibitor 1, the imidazole linker was first replaced with a pyrazole moiety to establish a polar C-H···water hydrogen-bonding interaction. Then, structure-based drug design was employed to modify lead molecule 2d in the P1' and P2' regions, with substituents interacting with key residues through various nonclassical interactions. As a result, a potent FXIa inhibitor 3f (Ki = 0.17 nM) was discovered. This compound demonstrated oral bioavailability in preclinical species (rat 36.4%, dog 80.5%, and monkey 43.0%) and displayed a dose-dependent antithrombotic effect in a rabbit arteriovenous shunt model of thrombosis.
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Affiliation(s)
- Guozhang Xu
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Zhijie Liu
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Xinkang Wang
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Tianbao Lu
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Renee L DesJarlais
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Tho Thieu
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Jing Zhang
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Zheng Huang Devine
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Fuyong Du
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Qiu Li
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Cynthia M Milligan
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Paul Shaffer
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Peder E Cedervall
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - John C Spurlino
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Christopher F Stratton
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Beth Pietrak
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Lawrence M Szewczuk
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Victoria Wong
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Ruth A Steele
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Wouter Bruinzeel
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Madhu Chintala
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Jose Silva
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Michael D Gaul
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Mark J Macielag
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
| | - Ravi Nargund
- Janssen Research & Development, L.L.C., 1400 McKean Road, Spring House, Pennsylvania 19477-0776, United States
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Ajabnoor AM, Zghebi SS, Parisi R, Ashcroft DM, Rutter MK, Doran T, Carr MJ, Mamas MA, Kontopantelis E. Incidence of nonvalvular atrial fibrillation and oral anticoagulant prescribing in England, 2009 to 2019: A cohort study. PLoS Med 2022; 19:e1004003. [PMID: 35671329 PMCID: PMC9173622 DOI: 10.1371/journal.pmed.1004003] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 04/28/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, and AF incidence is expected to increase. Guidelines recommend using oral anticoagulants (OACs) to prevent the development of stroke. However, studies have reported the frequent underuse of OACs in AF patients. The objective of this study is to describe nonvalvular atrial fibrillation (NVAF) incidence in England and assess the clinical and socioeconomic factors associated with the underprescribing of OACs. METHODS AND FINDINGS We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink (CPRD) database to identify patients with NVAF aged ≥18 years and registered in English general practices between 2009 and 2019. Annual incidence rate of NVAF by age, deprivation quintile, and region was estimated. OAC prescribing status was explored for patients at risk for stroke and classified into the following: OAC, aspirin only, or no treatment. We used a multivariable multinomial logistic regression model to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) of the factors associated with OAC or aspirin-only prescribing compared to no treatment in patients with NVAF who are recommended to take OAC. The multivariable regression was adjusted for age, sex, comorbidities, socioeconomic status, baseline treatment, frailty, bleeding risk factors, and takes into account clustering by general practice. Between 2009 and 2019, 12,517,191 patients met the criteria for being at risk of developing NVAF. After a median follow-up of 4.6 years, 192,265 patients had an incident NVAF contributing a total of 647,876 person-years (PYR) of follow-up. The overall age-adjusted incidence of NVAF per 10,000 PYR increased from 20.8 (95% CI: 20.4; 21.1) in 2009 to 25.5 (25.1; 25.9) in 2019. Higher incidence rates were observed for older ages and males. Among NVAF patients eligible for anticoagulation, OAC prescribing rose from 59.8% (95% CI: 59.0; 60.6) in 2009 to 83.2% (95% CI: 83.0; 83.4) in 2019. Several conditions were associated with lower risk of OAC prescribing: dementia [RRR 0.52 (0.47; 0.59)], liver disease 0.58 (0.50; 0.67), malignancy 0.74 (0.72; 0.77), and history of falls 0.82 (0.78; 0.85). Compared to white ethnicity, patients from black and other ethnic minorities were less likely to receive OAC; 0.78 (0.65; 0.94) and 0.76 (0.64; 0.91), respectively. Patients living in the most deprived areas were less likely to receive OAC 0.85 (0.79; 0.91) than patients living in the least deprived areas. Practices located in the East of England were associated with higher risk of prescribing aspirin only over no treatment than practices in London (RRR 1.22; 95% CI 1.02 to 1.45). The main limitation of this study is that these findings depends on accurate recording of conditions by health professionals and the inevitable residual confounding due to lack of data on certain factors that could be associated with under-prescribing of OACs. CONCLUSIONS The incidence of NVAF increased between 2009 and 2015, before plateauing. Underprescribing of OACs in NVAF is associated with a range of comorbidities, ethnicity, and socioeconomic factors, demonstrating the need for initiatives to reduce inequalities in the care for AF patients.
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Affiliation(s)
- Alyaa M. Ajabnoor
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
- Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester, United Kingdom
| | - Salwa S. Zghebi
- Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester, United Kingdom
| | - Rosa Parisi
- Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester, United Kingdom
| | - Darren M. Ashcroft
- Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- NIHR Greater Manchester Patient Safety Translational Research Centre (PSTRC), University of Manchester, Manchester, United Kingdom
| | - Martin K. Rutter
- Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre (MAHSC), The University of Manchester, Manchester, United Kingdom
- Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Tim Doran
- Department of Health Sciences, Seebohm Rowntree Building, University of York, York, United Kingdom
| | - Matthew J. Carr
- Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- NIHR Greater Manchester Patient Safety Translational Research Centre (PSTRC), University of Manchester, Manchester, United Kingdom
| | - Mamas A. Mamas
- Keele Cardiovascular Research Group, Centre for Prognosis Research, Institute for Primary Care and Health Sciences, Keele University, Keele, United Kingdom
| | - Evangelos Kontopantelis
- Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester, United Kingdom
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Belenkov YN, Popova LV, Ilgisonis SI. [Management of patients with atrial fibrillation and minor bleeding during therapy with direct oral anti-coagulants]. KARDIOLOGIIA 2021; 61:72-81. [PMID: 35057724 DOI: 10.18087/cardio.2021.12.n1872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 10/10/2021] [Accepted: 10/29/2021] [Indexed: 06/14/2023]
Abstract
The recommended tactics for prevention of thromboembolic complications of atrial fibrillation (AF) is the oral anticoagulant (OAC) treatment. The drugs of choice for preventing stroke for most patients with AF, excluding some valvular defects, are direct OACs (DOACS). Regardless of the drug class, all anticoagulants, even at appropriate doses, increase the risk of bleeding. However, the development of minor bleedings is not an absolute indication for DOAC withdrawal. This review presents a tactics for management of patients with minor bleeding associated with the DOAC treatment.
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Affiliation(s)
- Yu N Belenkov
- I.M. Sechenov First Moscow State Medical University, Moscow
| | - L V Popova
- I.M. Sechenov First Moscow State Medical University, Moscow
| | - S I Ilgisonis
- I.M. Sechenov First Moscow State Medical University, Moscow
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18
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Mu G, Zhang H, Liu Z, Xie Q, Zhou S, Wang Z, Wang Z, Hu K, Hou J, Zhao N, Xiang Q, Cui Y. Standard- vs. low-dose rivaroxaban in patients with atrial fibrillation: a systematic review and meta-analysis. Eur J Clin Pharmacol 2021; 78:181-190. [PMID: 34651200 DOI: 10.1007/s00228-021-03226-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 09/23/2021] [Indexed: 01/27/2023]
Abstract
PURPOSE Low-dose rivaroxaban is often given to patients with atrial fibrillation (AF) around the world, but the rationale for its use remains unclear. We aimed to compare the efficacy and safety of standard- or low-dose rivaroxaban in patients with AF through systematic review of literature with meta-analysis. METHODS We searched PubMed, Web of Science, EMBASE, Clinical Trials.gov, the Cochrane Library, and Bayer trial website from inception of each database until June 2020. Randomized controlled trials (RCTs) and cohort studies were included in the meta-analysis. A random-effects model was employed to calculate the pooled effect estimates. RESULTS Two RCTs and 17 cohort studies were included in the qualitative analysis. Indirect comparison of RCTs showed no significant difference between the two rivaroxaban dosages in risk of efficacy or safety outcomes (p > 0.05). Indirect comparison of cohort studies showed a lower risk of MACE among Caucasians in standard-dose group (HR 0.779; 95% CI 0.687-0.884; p < 0.001). Bleeding outcomes did not differ significantly between the two dosage regimens in Asian or Caucasian populations, except that the standard dose was associated with higher risk of major bleeding among elderly Caucasian patients (HR 1.329; 95% CI 1.141-1.547; p < 0.001). The quality of evidence was rated ranging from very low to low for all the efficacy and safety outcomes. CONCLUSION In Caucasians with AF, standard-dose rivaroxaban may prevent MACE significantly better than low-dose treatment. Further studies in Asians are needed to verify the advantages of the standard dose.
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Affiliation(s)
- Guangyan Mu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Hanxu Zhang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Zhiyan Liu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Qiufen Xie
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Shuang Zhou
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Zining Wang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Zhe Wang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Kun Hu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Jingyi Hou
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Nan Zhao
- Department of Pharmacy, Peking University First Hospital, Beijing, China
- School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Qian Xiang
- Department of Pharmacy, Peking University First Hospital, Beijing, China.
| | - Yimin Cui
- Department of Pharmacy, Peking University First Hospital, Beijing, China.
- School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.
- Institute of Clinical Pharmacology, Peking University, Beijing, China.
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19
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Lignosulfonic Acid Sodium Is a Noncompetitive Inhibitor of Human Factor XIa. Pharmaceuticals (Basel) 2021; 14:ph14090886. [PMID: 34577586 PMCID: PMC8466798 DOI: 10.3390/ph14090886] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 08/28/2021] [Accepted: 08/29/2021] [Indexed: 12/20/2022] Open
Abstract
The anticoagulant activity of lignosulfonic acid sodium (LSAS), a non-saccharide heparin mimetic, was investigated in this study. LSAS is a relatively safe industrial byproduct with similar polyanionic characteristics to that of heparin. Human plasma clotting assays, fibrin polymerization testing, and enzyme inhibition assays were exploited to investigate the anticoagulant activity of LSAS. In normal human plasma, LSAS selectively doubled the activated partial thromboplastin time (APTT) at ~308 µg/mL. Equally, LSAS doubled APTT at ~275 µg/mL in antithrombin-deficient plasma. Yet, LSAS doubled APTT at a higher concentration of 429 µg/mL using factor XI-deficient plasma. LSAS did not affect FXIIIa-mediated fibrin polymerization at 1000 µg/mL. Enzyme assays revealed that LSAS inhibits factor XIa (FXIa) with an IC50 value of ~8 μg/mL. LSAS did not inhibit thrombin, factor IXa, factor Xa, factor XIIIa, chymotrypsin, or trypsin at the highest concentrations tested and demonstrated significant selectivity against factor XIIa and plasmin. In Michaelis–Menten kinetics, LSAS decreased the VMAX of FXIa hydrolysis of a tripeptide chromogenic substrate without significantly changing its KM indicating an allosteric inhibition mechanism. The inhibitor also disrupted the generation of FXIa–antithrombin complex, inhibited factor XIIa-mediated and thrombin-mediated activation of the zymogen factor XI to FXIa, and competed with heparin for binding to FXIa. Its action appears to be reversed by protamine sulfate. Structure–activity relationship studies demonstrated the advantageous selectivity and allosteric behavior of LSAS over the acetylated and desulfonated derivatives of LSAS. LSAS is a sulfonated heparin mimetic that demonstrates significant anticoagulant activity in human plasma. Overall, it appears that LSAS is a potent, selective, and allosteric inhibitor of FXIa with significant anticoagulant activity in human plasma. Altogether, this study introduces LSAS as a promising lead for further development as an anticoagulant.
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Paquette M, Fadahunsi O, Wang M, Healey JS, Parkash R, Quayyum S, Khan M, Nieuwlaat R. Systematic review of treatment gaps in oral anticoagulant use in atrial fibrillation. THROMBOSIS UPDATE 2021. [DOI: 10.1016/j.tru.2021.100053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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21
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Kennedy C, Gabr A, McCormack J, Collins R, Barry M, Harbison J. The association between increasing oral anticoagulant prescribing and atrial fibrillation related stroke in Ireland. Br J Clin Pharmacol 2021; 88:178-186. [PMID: 34131941 DOI: 10.1111/bcp.14938] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 02/12/2021] [Accepted: 05/24/2021] [Indexed: 11/26/2022] Open
Abstract
AIMS Recent increases in the number of patients with atrial fibrillation (AF) prescribed oral anticoagulants (OAC) are evident in Ireland and internationally, largely due to the availability of direct oral anticoagulants (DOACs). This study aimed to determine the rate of stroke in the context of increasing anticoagulation utilisation, with a focus on AF-related ischaemic stroke (IS). METHODS Dispensing data for OACs were identified for the period 2010-2018 as well as hospital discharges for IS (2005-2018). Irish National Stroke Register data were used to elucidate the characteristics of patients with acute ischaemic stroke. RESULTS The number of patients prescribed OACs increased by 94% from 2010-2018 with a significant change from 2013 (β = 2.57, P = .038), associated with a large increase in the number of patients on DOACs. There was 3.3-fold increase in expenditure on OACs nationally from 2013 to 2018, of which 94% was DOAC related. Using the 2013 timepoint, ischaemic stroke rates until 2018 did not show a significant deviation from the previous trend (β = 0.00, P = .898). The percentage of AF-related ischaemic stroke was stable from 2013 to 2017 with a 4.5% decrease in 2018. The percentage of ischaemic stroke patients with previously diagnosed AF decreased from 2013 to 2018; however, there was an increase in the percentage of ischaemic strokes while on OAC in this cohort. CONCLUSION Large increases in OAC utilisation have not resulted in changes in ischaemic stroke rates at a national level. The percentage of ischaemic strokes with a previous diagnosis of AF has decreased indicating a possible benefit from greater OAC utilisation. However, the percentage presenting with an ischaemic stroke while on OAC treatment is increasing. The increase in patients presenting with stroke while treated with OAC may largely reflect the national increase in patients prescribed DOACs but the findings raise concerns about treatment failures. The real-world effectiveness of DOACs requires further examination.
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Affiliation(s)
- Cormac Kennedy
- Department of Pharmacology and Therapeutics, Health Sciences Centre, Trinity College Dublin, Dublin 8, Ireland.,Department of Pharmacology, St James Hospital, Dublin 8, Ireland
| | - Ahmed Gabr
- Department of Pharmacology and Therapeutics, Health Sciences Centre, Trinity College Dublin, Dublin 8, Ireland
| | - Joan McCormack
- National Office of Clinical Audit, St Stephens Green, Dublin, Ireland
| | - Rónán Collins
- Department Geriatrics and Stroke Medicine, Tallaght University Hospital, Dublin, Ireland
| | - Michael Barry
- Department of Pharmacology and Therapeutics, Health Sciences Centre, Trinity College Dublin, Dublin 8, Ireland.,Department of Pharmacology, St James Hospital, Dublin 8, Ireland
| | - Joe Harbison
- Mercer's Institute for Successful Ageing, St James Hospital, Dublin, Ireland.,Discipline of Medical Gerontology, School of Medicine, Trinity College Dublin, Ireland
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22
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Arbel A, Abu-Ful Z, Preis M, Cohen S, Saliba W. Implementation of oral anticoagulation treatment guidelines in patients with newly diagnosed atrial fibrillation. Br J Clin Pharmacol 2021; 87:4747-4755. [PMID: 33982796 DOI: 10.1111/bcp.14899] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 05/04/2021] [Accepted: 05/09/2021] [Indexed: 12/13/2022] Open
Abstract
AIMS Oral anticoagulants (OACs) are considered the mainstay in preventing stroke in atrial fibrillation (AF). OAC treatment remains suboptimal among AF patients, even after the introduction of direct oral anticoagulants (DOACs). We aimed to assess trends overtime and current implementation of OAC treatment guidelines in AF, using a large dataset of real world data from Israel. METHODS This is a retrospective cohort study that includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed nonvalvular AF between January 2014 and December 2019 with CHA2 DS2 -VASc score ≥2. OAC treatment rates were calculated and multivariate regression models were used to identify predictors of OACs initiation. RESULTS Overall, 46 531 patients were included in the study. The 3-months cumulative OAC treatment rates increased consistently over the years: 46.9% (95% confidence interval, 46.1-47.7%), 54.9% (54.1-55.6%) and 61.7% (60.9-62.4%) during 2014-2015, 2016-2017 and 2018-2019, respectively. DOACs constituted 51.3% of prescribed OACs in 2014-2015 and increased to 95.1% during 2018-2019. On multivariate analyses, the likelihood of OACs initiation among AF patients increased across the years and across higher socioeconomic classes, and was more likely among females, Jews, statins users and patients previously screened for colorectal cancer, but less likely among smokers and patients with impaired renal function. The likelihood of treatment increased with higher CHA2 DS2 -VASc score and decreased with higher HAS-BLED score. CONCLUSION Despite the increasing OAC treatment rates among high-risk AF patients, mainly attributed to the expanding DOAC use, OAC treatment scope is still far from optimal.
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Affiliation(s)
- Anat Arbel
- Department of Internal Medicine B, Lady Davis Carmel Medical Center, Haifa, Israel
| | - Zomoroda Abu-Ful
- Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel
| | - Meir Preis
- Institute of Hematology, Lady Davis Carmel Medical Center, Haifa, Israel.,Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Shai Cohen
- Department of Internal Medicine B, Lady Davis Carmel Medical Center, Haifa, Israel.,Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Walid Saliba
- Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.,Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Fastner C, Brachmann J, Lewalter T, Zeymer U, Sievert H, Borggrefe M, Nienaber CA, Weiß C, Pleger ST, Ince H, Maier J, Achenbach S, Sigusch HH, Hochadel M, Schneider S, Senges J, Akin I. Left atrial appendage closure in patients with chronic kidney disease: results from the German multicentre LAARGE registry. Clin Res Cardiol 2021; 110:12-20. [PMID: 32296971 PMCID: PMC7806558 DOI: 10.1007/s00392-020-01638-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 03/23/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Chronic kidney disease (CKD) is associated with an increased complication rate after cardiac interventions. Although CKD has a high prevalence among atrial fibrillation patients, the impact of CKD on periprocedural complications and the outcome after an interventional left atrial appendage closure (LAAC) is unclear. The present study, therefore, aimed to investigate whether CKD influences the procedure's effectiveness and safety. METHODS LAARGE is a prospective, non-randomised registry. LAAC was conducted with different standard commercial devices, and the follow-up period was one year. CKD was defined by an eGFR < 60 mL/min/1.73 m2, and subgroups were further analysed (i.e. eGFR < 15, 15-29, and 30-59 mL/min/1.73 m2, respectively). RESULTS Two hundred ninety-nine of 623 patients (48.0%) revealed a CKD. The prevalence of cardiovascular comorbidity, CHA2DS2-VASc score (4.9 vs. 4.2), and HAS-BLED score (4.3 vs. 3.5) was significantly higher in CKD patients (each p < 0.001). Implantation success was similarly high across all GFR groups (97.9%). Periprocedural MACCE (0.7 vs. 0.3%), and other major complications (4.7 vs. 3.7%) were comparably infrequent. Survival free of stroke was significantly lower among CKD patients within 1 year (82.0 vs. 93.0%; p < 0.001; consistent after adjustment for confounding factors), without significant accentuation in advanced CKD (i.e. eGFR < 30 mL/min/1.73 m2; p > 0.05 vs. eGFR 30-59 mL/min/1.73 m2). Non-fatal strokes were absolutely infrequent during follow-up (0 vs. 1.1%). Severe non-fatal bleedings were observed only among CKD patients (1.4 vs. 0%; p = 0.021). CONCLUSIONS Despite an increased cardiovascular risk profile of CKD patients, device implantation was safe, and LAAC was associated with effective stroke prevention across all CKD stages.
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Affiliation(s)
- Christian Fastner
- First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Johannes Brachmann
- Department of Cardiology, Angiology, and Pneumology, Second Medical Clinic, Coburg Hospital, Coburg, Germany
| | - Thorsten Lewalter
- Department of Medicine, Cardiology, and Intensive Care, Hospital Munich-Thalkirchen, Munich, Germany
| | - Uwe Zeymer
- Klinikum Ludwigshafen, Ludwigshafen am Rhein, Germany
| | - Horst Sievert
- CardioVascular Center (CVC) Frankfurt, Frankfurt, Germany
- Anglia Ruskin University, Chelmsford, UK
| | - Martin Borggrefe
- First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Christoph A Nienaber
- Cardiology and Aortic Center, Royal Brompton and Harefield NHS Foundation, Trust at Imperial College, London, UK
| | - Christian Weiß
- Department of Cardiology, Klinikum Lüneburg, Lüneburg, Germany
| | - Sven T Pleger
- Department of Internal Medicine III, Cardiology, Angiology, and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
| | - Hüseyin Ince
- Department of Cardiology, Rostock University Medical Center, Rostock, Germany
- Department of Cardiology, Vivantes Klinikum Am Urban & im Friedrichshain, Berlin, Germany
| | - Jens Maier
- Medical Department I, SLK-Kliniken Heilbronn GmbH, Klinikum am Gesundbrunnen, Heilbronn, Germany
| | | | - Holger H Sigusch
- Clinic for Internal Medicine I, Heinrich-Braun-Klinikum Zwickau gGmbH, Zwickau, Deutschland
| | - Matthias Hochadel
- Stiftung Institut für Herzinfarktforschung, Ludwigshafen am Rhein, Germany
| | - Steffen Schneider
- Stiftung Institut für Herzinfarktforschung, Ludwigshafen am Rhein, Germany
| | - Jochen Senges
- Stiftung Institut für Herzinfarktforschung, Ludwigshafen am Rhein, Germany
| | - Ibrahim Akin
- First Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg/Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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24
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Lin D, Chen Y, Yong J, Wu S, Zhou Y, Li W, Tan X, Liu R. Does Warfarin or Rivaroxaban at Low Anticoagulation Intensity Provide a Survival Benefit to Asian Patients With Atrial Fibrillation? Front Cardiovasc Med 2021; 8:768730. [PMID: 34901228 PMCID: PMC8655790 DOI: 10.3389/fcvm.2021.768730] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/03/2021] [Indexed: 02/05/2023] Open
Abstract
Background: Low-dose rivaroxaban and low-intensity warfarin are widely used in Asia for patients with atrial fibrillation (AF). However, in Asians, it is unclear whether low-dose rivaroxaban and low-intensity warfarin can improve the prognosis of AF. In this study, we investigate the survival benefits of low-dose rivaroxaban and low-intensity warfarin in Asian patients with AF in clinical practice. Methods: This cohort study used medical records in a single tertiary hospital in China, between 2019 and 2020, to identify patients with AF who used rivaroxaban or warfarin, or had no anticoagulant therapy. Follow-ups were performed through telephone contact or medical record review. Cox proportional hazards models were used to compare the risk of mortality of patients in the anticoagulant-untreated group vs. warfarin-treated groups and rivaroxaban-treated groups. Results: A total of 1727 AF patients, discharged between 2019 and 2020, were enrolled in this cohort, of which 873 patients did not use any anticoagulant, 457 patients received warfarin and 397 patients used rivaroxaban. Multivariable analysis showed that, of all the warfarin groups, patients with an international normalized ratio (INR) below 2, good INR control, or poor INR control had a significantly lower risk of mortality compared with that of patients without anticoagulants (HR 0.309, p = 0.0001; HR 0.387, p = 0.0238; HR 0.363, p < 0.0001). Multivariable Cox proportional hazard analyses also demonstrated that, compared with the no anticoagulant group, all rivaroxaban dosage groups (≤10 mg, HR 0.456, p = 0.0129; 15 mg, HR 0.246, p = 0.0003; 20 mg, HR 0.264, p = 0.0237) were significantly associated with a lower risk of mortality. Conclusion: Despite effects being smaller than observed with recommended optimal anticoagulation, the use of warfarin with an INR below 2, poor INR control and the use of low-dose rivaroxaban may still provide survival benefits, suggesting viable alternatives that enable physicians to better resolve decisional conflicts concerning the risks and benefits of anticoagulant therapies, as well as for patients in need of but unable to receive standard anticoagulant therapy due to bleeding risk or other factors, such as financial burden, concerns of adverse outcomes, as well as low treatment compliance and persistence.
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Affiliation(s)
- Dong Lin
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
| | - Yequn Chen
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Clinical Cohort Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Jian Yong
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Shiwan Wu
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Yan Zhou
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Weiping Li
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Clinical Cohort Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Xuerui Tan
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Clinical Cohort Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- *Correspondence: Xuerui Tan
| | - Ruisheng Liu
- Morsani College of Medicine, University of South Florida, Tampa, FL, United States
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25
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Deitelzweig S, Dhamane AD, Di Fusco M, Russ C, Rosenblatt L, Lingohr-Smith M, Lin J. Utilization of anticoagulants and predictors of treatment among hospitalized patients with atrial fibrillation in the USA. J Med Econ 2020; 23:1389-1400. [PMID: 33021129 DOI: 10.1080/13696998.2020.1832099] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To evaluate utilization of anticoagulants (ACs) and the predictors of treatment of patients with a diagnosis of atrial fibrillation (AF) during a hospital stay in the USA. METHODS Patients (≥18 years of age) who had a primary or secondary discharge diagnosis code of AF during a hospitalization (without a diagnosis of venous thromboembolism) were identified from the Premier Hospital database (1 January 2016-30 September 2017). AC treatments were examined during hospitalizations to assign AF patients into 3 study cohorts: those who received an oral AC (OAC), those who received parenteral AC only, and those who did not receive AC therapy. Multivariable logistic regression analyses were carried out to evaluate potential predictors of receiving parenteral AC only vs. OAC therapy, no AC therapy vs. OAC therapy, as well as the specific OAC drug choices. RESULTS Of the patients hospitalized with an AF diagnosis (n = 482,729; mean age: 74.7 years; 46.8% female; 82.9% White; 79.4% with Medicare), 42.6% received OAC therapy (most commonly, warfarin or apixaban), 35.3% parenteral AC only, and 22.2% no AC therapy. A key predictor of not receiving OAC therapy was having an AF diagnosis in the second position (applicable to 87.4% of study population). Greater comorbidity level and prior baseline bleeding were strong predictors of receiving parenteral AC only or not receiving any AC therapy vs. receiving OAC therapy. Predictors of receiving warfarin vs. apixaban included higher stroke risk and prior baseline bleeding. LIMITATIONS OAC utilization may have been underestimated since outpatient OAC utilization was not included in the analysis. CONCLUSIONS A substantial portion of hospitalized AF patients did not receive any AC therapy, particularly those patients with an AF diagnosis in the second position on hospital records. The predictors of inpatient AC treatment that were identified may be helpful in the clinical decision-making process for patients who are hospitalized with AF.
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Affiliation(s)
- Steven Deitelzweig
- Department of Hospital Medicine, Ochsner Clinic Foundation, New Orleans, LA, USA
- Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, USA
| | | | | | | | | | | | - Jay Lin
- Novosys Health, Green Brook, NJ, USA
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26
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Ng VWS, Siu CW, Chiu PKC, Kng CPL, Jamieson E, Wong ICK, Lam MPS. Understanding the barriers to using oral anticoagulants among long-term aspirin users with atrial fibrillation - a qualitative study. BMC Health Serv Res 2020; 20:1084. [PMID: 33238989 PMCID: PMC7691100 DOI: 10.1186/s12913-020-05947-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 11/19/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Despite international treatment guidelines currently advocating oral anticoagulants (OACs) as the only appropriate stroke prevention therapy for patients with atrial fibrillation (AF) and evidence that OACs can greatly reduce the risk of stroke with similar risk of bleeding compared with aspirin, the underuse of OACs in patients with AF is common globally, especially in Asia. This study aimed to identify the barriers to prescribing and using OACs among long-term aspirin users with AF. METHOD Face-to-face interviews were conducted with fourteen eligible patients with AF using a semi-structured interview guide. The interview recordings were transcribed verbatim and data was analyzed according to the principles of thematic analysis. RESULTS Five themes were developed: awareness of AF symptoms and diagnosis; knowledge and understanding of AF and stroke prevention therapy; role of decision-making in prescribing; willingness to switch from aspirin to OACs; and impact of OAC regimen on daily living. The majority of the patients were not aware of the symptoms and diagnosis of AF and only had a vague understanding of the illness and stroke prevention therapy, leading to their minimal involvement in decisions relating to their treatment. Some patients and their caregivers were particularly concerned about the bleeding complications from OACs and perceived aspirin to be a suitable alternative as they find the adverse effects from aspirin manageable and so preferred to remain on aspirin if switching to OACs was not compulsory. Lastly, the lifestyle modifications required when using warfarin, e.g. alternative dosing regimen, diet restriction, were seen as barriers to some patients and caregivers. CONCLUSION The findings revealed patients' knowledge gap in AF management which may be targeted using educational interventions to improve patients' understanding of AF and its management and hence encourage active participation in the decision-making of their treatment in the future.
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Affiliation(s)
- Vanessa W S Ng
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
| | - Chung-Wah Siu
- Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Patrick K C Chiu
- Division of Geriatrics, Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China
| | - Carolyn P L Kng
- Division of Geriatrics, Ruttonjee and Tang Shiu Kin Hospitals, Hong Kong SAR, China
| | - Elizabeth Jamieson
- Research Department of Practice and Policy, University College London School of Pharmacy, London, UK
| | - Ian C K Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China.,Research Department of Practice and Policy, University College London School of Pharmacy, London, UK
| | - May P S Lam
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China.
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27
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Kar S, Mottamal M, Al‐Horani RA. Discovery of Benzyl Tetraphosphonate Derivative as Inhibitor of Human Factor Xia. ChemistryOpen 2020; 9:1161-1172. [PMID: 33204588 PMCID: PMC7654249 DOI: 10.1002/open.202000277] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/08/2020] [Indexed: 12/14/2022] Open
Abstract
The inhibition of factor XIa (FXIa) is a trending paradigm for the development of new generations of anticoagulants without a substantial risk of bleeding. In this report, we present the discovery of a benzyl tetra-phosphonate derivative as a potent and selective inhibitor of human FXIa. Biochemical screening of four phosphonate/phosphate derivatives has led to the identification of the molecule that inhibited human FXIa with an IC50 value of ∼7.4 μM and a submaximal efficacy of ∼68 %. The inhibitor was at least 14-fold more selective to FXIa over thrombin, factor IXa, factor Xa, and factor XIIIa. It also inhibited FXIa-mediated activation of factor IX and prolonged the activated partial thromboplastin time of human plasma. In Michaelis-Menten kinetics experiment, inhibitor 1 reduced the VMAX of FXIa hydrolysis of a chromogenic substrate without significantly affecting its KM suggesting an allosteric mechanism of inhibition. The inhibitor also disrupted the formation of FXIa - antithrombin complex and inhibited thrombin-mediated and factor XIIa-mediated formation of FXIa from its zymogen factor XI. Inhibitor 1 has been proposed to bind to or near the heparin/polyphosphate-binding site in the catalytic domain of FXIa. Overall, inhibitor 1 is the first benzyl tetraphosphonate small molecule that allosterically inhibits human FXIa, blocks its physiological function, and prevents its zymogen activation by other clotting factors under in vitro conditions. Thus, we put forward benzyl tetra-phosphonate 1 as a novel lead inhibitor of human FXIa to guide future efforts in the development of allosteric anticoagulants.
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Affiliation(s)
- Srabani Kar
- Division of Basic Pharmaceutical Sciences College of PharmacyXavier University of LouisianaNew OrleansLA70125USA
| | - Madhusoodanan Mottamal
- RCMI Cancer Research Center & Department of ChemistryXavier University of LouisianaNew OrleansLA70125USA
| | - Rami A. Al‐Horani
- Division of Basic Pharmaceutical Sciences College of PharmacyXavier University of LouisianaNew OrleansLA70125USA
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Obaid M, Douiri A, Flach C, Prasad V, Marshall I. Can we prevent poststroke cognitive impairment? An umbrella review of risk factors and treatments. BMJ Open 2020; 10:e037982. [PMID: 32912953 PMCID: PMC7482478 DOI: 10.1136/bmjopen-2020-037982] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 07/15/2020] [Accepted: 07/27/2020] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES Cognitive impairment poststroke is progressive. We aimed to synthesise the existing evidence evaluating risk factors and the effects of treatments to prevent/improve cognitive function in patients who had a stroke with cognitive impairment. DESIGN Umbrella review. DATA SOURCE Medline, PsycINFO, EMBASE, Cochrane and PROSPERO were searched from inception until 11 June 2019. ELIGIBILITY CRITERIA Published systematic review (SR) that incorporated randomised controlled trials to investigate an intervention to improve poststroke cognitive impairment, or SR of longitudinal observational studies that evaluated the risk factors of this condition. No restrictions were applied. DATA EXTRACTION AND SYNTHESIS From each eligible study, details were recorded by one reviewer in a validated form. Grading of Recommendations, Assessment, Development and Evaluations criteria were used to assess our certainty level of each outcome, and A Measurement Tool to Assess Systematic Reviews 2 to assess quality. RESULTS Altogether, 3464 abstracts were retrieved, 135 full texts were evaluated and 22 SRs were included in the final analysis. From four SRs of observational studies, we found 19 significant associations with postulated risk factors, and those which we determined to be confident about were: atrial fibrillation (3 SRs, 25 original studies); relative risk 3.01 (1.96-4.61), ORs 2.4 (1.7-3.5) and 2.0 (1.4-2.8), leukoaraiosis, multiple and recurrent strokes, ORs 2.5 (1.9-3.4), 2.5 (1.9-3.1) and 2.3 (1.5-3.5), respectively. From 18 SRs of interventional trials, we found that interventions including physical activity or cognitive rehabilitation were enhancing cognitive function, while the certainty of the other interventions was rated low, due to limited methodological quality. CONCLUSIONS This review represents common risk factors related to poststroke cognitive impairment, in particular atrial fibrillation, and points to different interventions that warrant attention in the development of treatment strategies. Physical activity and cognitive rehabilitation interventions showed evidence of enhancing cognitive function; however, we could not recommend a change in practice yet, due to lack of strong evidence. PROSPERO REGISTRATION NUMBER CRD42018096667.
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Affiliation(s)
- Majed Obaid
- Primary Care and Public Health Sciences, Division of Health and Social Care Research, King's College London, London, UK
- Department of Community Medicine and Medical Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Abdel Douiri
- Primary Care and Public Health Sciences, Division of Health and Social Care Research, King's College London, London, UK
- National Institute for Health Research Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust, London, UK
| | - Clare Flach
- Primary Care and Public Health Sciences, Division of Health and Social Care Research, King's College London, London, UK
| | - Vibhore Prasad
- Primary Care and Public Health Sciences, Division of Health and Social Care Research, King's College London, London, UK
| | - Iain Marshall
- Primary Care and Public Health Sciences, Division of Health and Social Care Research, King's College London, London, UK
- National Institute for Health Research Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust, London, UK
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Giner-Soriano M, Cortes J, Gomez-Lumbreras A, Prat-Vallverdú O, Quijada-Manuitt MA, Morros R. The use and adherence of oral anticoagulants in Primary Health Care in Catalunya, Spain: A real-world data cohort study. Aten Primaria 2020; 52:529-538. [PMID: 32788057 PMCID: PMC7505898 DOI: 10.1016/j.aprim.2020.05.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 05/05/2020] [Accepted: 05/21/2020] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE We aimed to describe sociodemographic, comorbidities, co-medication and risk of thromboembolic events and bleeding in patients with NVAF initiating oral anticoagulants (OAC) for stroke prevention, and to estimate adherence and persistence to OAC. SETTING Primary Health Care (PHC) in the Catalan Health Institute (ICS), Catalunya, Spain. PARTICIPANTS All NVAF adult patients initiating OAC for stroke prevention in August 2013-December 2015. METHODS Population-based cohort study. Persistence was measured in patients initiating OAC in August 2013-December 2014. DATA SOURCE SIDIAP, which captures electronic health records from PHC in the (ICS), covering approximately 5.8 million people. RESULTS 51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 (62.7%) initiated acenocoumarol. Mean age was 72.8 years (SD 12.3) and 49.4% were women. Platelet-aggregation inhibitors were taken by 9105 (17.6%) of the patients. Persistence and adherence were estimated up to the end of follow-up. For 22,075 patients, persistence was higher among the non-naive patients [n=258 (61.7%)] than among the naive [n=11,502 (53.1%)]. Adherence was estimated for patients initiating DOAC and it was similar in naive and non-naive patients. Among the naive to DOAC treatment, those starting rivaroxaban showed a highest proportion [(n=360 (80.1%)] of good adherence at implementation (MPR>80%) while patients starting dabigatran were less adherent [n=203 (47.8%)]. CONCLUSIONS Acenocoumarol was the most frequently prescribed OAC as first therapy in NVAF patients. Non-naive to DOAC showed better persistence than naive. Rivaroxaban showed higher proportion of adherent patients during the implementation phase than apixaban and dabigatran the lowest.
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Affiliation(s)
- Maria Giner-Soriano
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Institut Català de la Salut, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain
| | - Jordi Cortes
- Department d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Spain
| | - Ainhoa Gomez-Lumbreras
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, Girona, Spain.
| | - Oriol Prat-Vallverdú
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
| | - Mª Angeles Quijada-Manuitt
- Department of Clinical Pharmacology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Pathology and Experimental Therapeutics, Unitat Docent Campus de Bellvitge, Universitat de Barcelona, L'Hospitalet (Barcelona), Spain
| | - Rosa Morros
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; Institut Català de la Salut, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain; UICEC IDIAP Jordi Gol, Plataforma SCReN, Barcelona, Spain
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30
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Metzgier-Gumiela A, Skonieczny G, Konieczyńska M, Desteghe L, Heidbuchel H, Undas A. Minor bleeding affects the level of knowledge in patients with atrial fibrillation on oral anticoagulant therapy. Int J Clin Pract 2020; 74:e13483. [PMID: 32003070 DOI: 10.1111/ijcp.13483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 01/15/2020] [Accepted: 01/26/2020] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Anticoagulant therapy in patients with atrial fibrillation (AF) increases the risk of minor bleeding, which is mostly accepted by patients. We aimed to assess whether continuation of anticoagulation despite minor bleeding is associated with a higher level of knowledge on AF and anticoagulation. METHODS AND RESULTS In 1525 patients with AF on oral anticoagulation who completed the Jessa AF Knowledge Questionnaire (JAKQ) (median age: 72 years [range, 65-79 years]; men: 54.6%), persistent self-reported minor bleeding was recorded. Minor bleeding was observed in 567 patients (37.2%) including 224 patients (39.5%) on vitamin K antagonists (VKAs) and 343 (60.5%) on non-vitamin K antagonist oral anticoagulants (NOACs). The risk of minor bleeding was lower among patients on NOACs than on VKAs (33.5% vs 44.6%; P < .0001). Multiple logistic regression showed that minor bleeding was associated with the use of NOACs (odds ratio [OR] 0.75; 95% CI 0.59-0.97), female gender (OR 2.19; 95% CI, 1.74-2.75; P < .0001), history of major bleeding (OR 2.85; 95% CI, 1.96-4.14; P < .0001), time since AF diagnosis (OR 1.04; 95% CI, 1.01-1.06; P < .0001), concomitant vascular disease (OR 1.43; 95% CI, 1.10-1.87; P = .0008) and diabetes mellitus (OR 1.3; 95% CI, 1.02-1.65, P = .03). Patients with minor bleeding, compared with the remaining subjects scored higher on the JAKQ (median, 62.5% vs 56.2%, respectively, P < .0001). The former group knew more about the purpose of anticoagulant therapy (71.8% vs 65.7%, P = .01) and bleeding as its key side effect (66.1% vs 52.7%, P < .0001), and were better informed on the safest painkillers to use in combination with anticoagulation (48% vs 35%, P < .0001). CONCLUSION This study suggests that AF patients who accept persistent minor bleeding have better knowledge on the disease and anticoagulation therapy compared with those free of these side effects.
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Affiliation(s)
| | | | | | - Lien Desteghe
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
- Heart Centre Hasselt, Jessa Hospital, Hasselt, Belgium
- University of Antwerp and Antwerp University Hospital, Edegem, Belgium
| | - Hein Heidbuchel
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
- Heart Centre Hasselt, Jessa Hospital, Hasselt, Belgium
- University of Antwerp and Antwerp University Hospital, Edegem, Belgium
| | - Anetta Undas
- John Paul II Hospital, Krakow, Poland
- Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland
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31
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Tzikas A, Samaras A, Kartas A, Vasdeki D, Fotos G, Dividis G, Paschou E, Forozidou E, Tsoukra P, Kotsi E, Goulas I, Karvounis H, Giannakoulas G. Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with non-valvular Atrial Fibrillation (MISOAC-AF): a randomized clinical trial. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2020; 7:f63-f71. [PMID: 32339234 DOI: 10.1093/ehjcvp/pvaa039] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 03/05/2020] [Accepted: 04/21/2020] [Indexed: 12/13/2022]
Abstract
AIMS We aimed to assess the impact of an educational, motivational intervention on the adherence to oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (AF). METHODS AND RESULTS Hospitalized patients with non-valvular AF who received OAC were randomly assigned to usual medical care or a proactive intervention, comprising motivational interviewing, and tailored counselling on medication adherence. The primary study outcome was adherence to OAC at 1 year, which was evaluated according to proportion of days covered (PDC) by OAC regimens and was assessed through nationwide registers of prescription claims. Secondary outcomes included the rate of persistence to OAC, gaps in treatment, and clinical events. A total of 1009 patients were randomized, 500 in the intervention group and 509 in the control group. At 1-year follow-up, 77.2% (386/500) of patients in the intervention group were adherent (PDC > 80%), compared with 55% (280/509) in the control group [adjusted odds ratio (aOR) 2.84, 95% confidence interval (CI) 2.14-3.75; P < 0.001]. Mean PDC ± standard deviation was 0.85 ± 0.26 and 0.75 ± 0.31, respectively (P < 0.001). Patients that received the intervention were more likely to persist in their OAC therapy at 1 year (aOR 2.42, 95% CI 1.71-3.41; P < 0.001). Usual medical care was associated with more major (≥3 months) treatment gaps (aOR 2.39, 95% CI 1.76-3.26; P < 0.001). Clinical events over a median follow-up period of 2 years did not differ among treatment groups. CONCLUSION In patients receiving OAC therapy for non-valvular AF, a multilevel motivational intervention significantly improved medication adherence and rate of therapy persistence, and reduced major gaps in treatment. No significant impact on clinical outcomes was observed. TRIAL REGISTRATION NUMBER NCT02941978.
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Affiliation(s)
- Apostolos Tzikas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece.,Department of Cardiology, Interbalkan European Medical Center, Asklipiou 10, Pylaia, Thessaloniki 55535, Greece
| | - Athanasios Samaras
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Anastasios Kartas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Dimitra Vasdeki
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - George Fotos
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - George Dividis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Eleni Paschou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Evropi Forozidou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Paraskevi Tsoukra
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Eleni Kotsi
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Ioannis Goulas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - Haralambos Karvounis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
| | - George Giannakoulas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, Thessaloniki 54636, Greece
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Hjelholt TJ, Johnsen SP, Brynningsen PK, Pedersen AB. Association of CHA 2 DS 2 -VASc Score with Stroke, Thromboembolism, and Death in Hip Fracture Patients. J Am Geriatr Soc 2020; 68:1698-1705. [PMID: 32294240 DOI: 10.1111/jgs.16452] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 03/06/2020] [Accepted: 03/13/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Patients undergoing hip fracture surgery have a 10 times increased risk of stroke compared with the general population. We aimed to evaluate the association between the CHA2 DS2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke/TIA [transient ischemic attack]/systemic embolism (2 points), vascular disease, age 65-74 years, and female sex) score and the risk of stroke, thromboembolism, and all-cause mortality in patients with hip fracture with or without atrial fibrillation (AF). DESIGN Nationwide prospective cohort study. SETTING Danish hospitals. PARTICIPANTS Subjects were all incident hip fracture patients in Denmark age 65 years and older with surgical repair procedures between 2004 and 2016 (n = 78,096). Participants were identified using the Danish Multidisciplinary Hip Fracture Registry. MEASUREMENTS We calculated incidence rates, cumulative incidences, and hazard ratios (HRs) with 95% confidence intervals (CIs) by CHA2 DS2 -VASc score, stratified on AF history. RESULTS The cumulative incidence of ischemic stroke 1 year after hip fracture increased with ascending CHA2 DS2 -VASc score, and it was 1.9% for patients with a score of 1 and 8.6% for patients with a score above 5 in the AF group. Corresponding incidences in the non-AF group were 1.6% and 7.6%. Compared with a CHA2 DS2 -VASc score of 1, adjusted HRs were 5.53 (95% CI = 1.37-22.24) among AF patients and 4.91 (95% CI = 3.40-7.10) among non-AF patients with a score above 5. A dose-response-like association was observed for all cardiovascular outcomes. All-cause mortality risks and HRs were substantially higher for all CHA2 DS2 -VASc scores above 1 in both the AF group and the non-AF group. CONCLUSION Among patients with hip fracture, a higher CHA2 DS2 -VASc score was associated with increased risk of stroke, thromboembolism, and death. This finding applied both to patients with and without AF. Patients with high CHA2 DS2 -VASc scores had almost similar absolute risks for cardiovascular outcomes, irrespective of AF. J Am Geriatr Soc 68:1698-1705, 2020.
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Affiliation(s)
- Thomas J Hjelholt
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Søren P Johnsen
- Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | | | - Alma B Pedersen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
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Hernandez I, He M, Brooks MM, Saba S, Gellad WF. Adherence to Anticoagulation and Risk of Stroke Among Medicare Beneficiaries Newly Diagnosed with Atrial Fibrillation. Am J Cardiovasc Drugs 2020; 20:199-207. [PMID: 31523759 PMCID: PMC7073283 DOI: 10.1007/s40256-019-00371-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
INTRODUCTION The objective of this study was to compare the risk of stroke in atrial fibrillation (AF) with adherent use of oral anticoagulation (OAC), non-adherent use, and non-use of OAC. METHODS Using 2013-2016 Medicare claims data, we identified patients newly diagnosed with AF in 2014-2015 and collected prescriptions filled for OAC in the 12 months after AF diagnosis (n = 39,272). We categorized participants each day into three time-dependent exposures: adherent use (≥ 80% of the previous 30 days covered with OAC), non-adherent use (0-80% covered with OAC), and non-use (0%). We constructed Cox proportional hazards models to estimate the association between time-dependent exposures and time to stroke, adjusting for demographics and clinical characteristics. RESULTS The sample included 39,272 patients. Study participants spent 35.0% of the follow-up period in the adherent use exposure category, 10.9% in the non-adherent category, and 54.0% in the non-use category. OAC adherent use [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.52-0.74] and non-adherent use (HR 0.74; 95% CI 0.57-0.95) were associated with lower hazards of stroke than non-use. Adherent use of DOAC (HR 0.54; 95% CI 0.42-0.69) and warfarin (HR 0.70; 95% CI 0.56-0.89) was associated with lower risk of stroke than non-use, but the risk of stroke did not statistically differ between DOAC and warfarin adherent use (HR 0.77; 95% CI 0.56-1.04). DISCUSSION Although adherence to OAC reduces stroke risk by nearly 40%, newly diagnosed AF patients in Medicare adhere to OAC on average only one third of the first year after AF diagnosis.
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Affiliation(s)
- Inmaculada Hernandez
- Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, 3609 Forbes Avenue, Room 103, Pittsburgh, PA, 15261, USA.
| | - Meiqi He
- Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, 3609 Forbes Avenue, Room 103, Pittsburgh, PA, 15261, USA
| | - Maria M Brooks
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Samir Saba
- Heart and Vascular Institute, University of Pittsburgh Medical Centre, Pittsburgh, PA, USA
| | - Walid F Gellad
- Division of General Internal Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
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Santos J, António N, Rocha M, Fortuna A. Impact of direct oral anticoagulant off-label doses on clinical outcomes of atrial fibrillation patients: A systematic review. Br J Clin Pharmacol 2020; 86:533-547. [PMID: 31631392 DOI: 10.1111/bcp.14127] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 08/14/2019] [Accepted: 09/07/2019] [Indexed: 12/23/2022] Open
Abstract
AIMS Worldwide observational studies are evidencing discordance between guidelines and real-world practice regarding direct oral anticoagulant drug (DOAC) doses. This systematic review summarizes and evaluate DOACs use in real-world practice. METHODS This review was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines searching PubMed (MEDLINE) and Medscape databases. RESULTS Data from 75 studies showed that most of the patients treated with DOACs for stroke prevention in atrial fibrillation received doses in accordance to the guidelines. However, a significant number of patients received off-label doses (25-50% in most of the studies evaluated). DOAC overdosing was associated with increased all-cause mortality and worse bleeding events while underdosing was associated with increased cardiovascular hospitalization and, particularly for apixaban, with a nearly 5-fold increased risk of stroke. CONCLUSION Patients prescribed with off-label DOAC doses did not receive the full benefit of anticoagulation and presented an increased risk of stroke, bleeding and/or adverse effects.
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Affiliation(s)
- Joana Santos
- Laboratory of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - Natália António
- Laboratory of Pharmacology, Faculty of Medicine, University of Coimbra, Portugal.,Cardiology Department, Coimbra Hospital and Universitary Centre, Portugal.,Coimbra Institute for Clinical and Biomedical Research (iCBR), Coimbra, Portugal
| | - Marília Rocha
- Pharmaceutical Service, Coimbra Hospital and Universitary Centre, Portugal
| | - Ana Fortuna
- Laboratory of Pharmacology and Pharmaceutical Care, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.,Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.,CIBIT/ICNAS - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal
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35
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Della Rocca DG, Horton RP, Di Biase L, Bassiouny M, Al-Ahmad A, Mohanty S, Gasperetti A, Natale VN, Trivedi C, Gianni C, Burkhardt JD, Gallinghouse GJ, Hranitzky P, Sanchez JE, Natale A. First Experience of Transcatheter Leak Occlusion With Detachable Coils Following Left Atrial Appendage Closure. JACC Cardiovasc Interv 2020; 13:306-319. [DOI: 10.1016/j.jcin.2019.10.022] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 10/07/2019] [Accepted: 10/08/2019] [Indexed: 10/25/2022]
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Murphy A, Kirby A, Bradley C. Monitoring of atrial fibrillation in primary care patients prescribed direct oral anticoagulants for stroke prevention. Ir J Med Sci 2020; 189:961-966. [PMID: 31900842 DOI: 10.1007/s11845-019-02150-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 11/20/2019] [Indexed: 01/14/2023]
Abstract
BACKGROUND Direct oral anticoagulants (DOACs) are widely marketed as medicines that do not require routine laboratory monitoring. However, they do have complex pharmacological properties and side effects; hence prescribing and monitoring guidelines, such as the European Heart Rhythm Association (EHRA) guidelines, have emerged. These advocate monitoring for renal and hepatic impairment; bleeding episodes; liver function; co-medication; circulation, and occurrence of side effects. Though 3 to 6 month follow-up is advocated, this is currently not routine, and its implementation creates a potential obligation for general practitioners (GPs) managing atrial fibrillation (AF) patients in the community. AIMS This study investigates the frequency, the type of follow-up, and the factors that influenced follow-up among Irish GPs, who prescribed DOACs to patients with AF, to prevent strokes in 2015. METHODS The frequency and type of follow-up care is estimated, and a count model regression analysis is applied to determine the GP and practice characteristics that are associated with the implementation of follow-up. RESULTS The EHRA guidelines most frequently followed were those pertaining to renal function (82%), bleeding episodes (71%), liver function (69%), circulation (54%), and side effects (55%). The regression analysis revealed that female GPs (P = 0.05) and GPs who follow all seven guidelines (P = 0.06) practice more frequent follow-up while those in training practices (P = 0.09) provide less frequent follow-up. CONCLUSIONS Results show that there was incomplete adherence to the 2013 EHRA prescribing guidelines with only 24% adhering to all seven guidelines, and patient follow-up was less frequent than has been suggested.
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Affiliation(s)
- Aileen Murphy
- Department of Economics, Cork University Business School, University College Cork, Aras na Laoi, Western Rd., Cork, Ireland.
| | - Ann Kirby
- Department of Economics, Cork University Business School, University College Cork, Aras na Laoi, Western Rd., Cork, Ireland
| | - Colin Bradley
- Department of General Practice, School of Medicine, Western Gateway Building, University College Cork, Cork, Ireland
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Al-Horani RA. Factor XI(a) inhibitors for thrombosis: an updated patent review (2016-present). Expert Opin Ther Pat 2019; 30:39-55. [PMID: 31847619 DOI: 10.1080/13543776.2020.1705783] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Introduction: Anticoagulation without bleeding is an ideal goal in treating thrombosis, however, this goal has not been achieved. All current anticoagulants are associated with significant bleeding which limits their safe use. Genetic and pharmacological findings indicate that factor XIa is a key player in thrombosis, yet it is a relatively marginal one in hemostasis. Thus, factor XIa and its zymogen offer a unique opportunity to develop anticoagulants with low bleeding risk.Areas covered: A survey of patent literature has retrieved more than 50 patents on the discovery of novel therapeutics targeting factor XI(a) since 2016. Small molecules, monoclonal antibodies, oligonucleotides, and polypeptides have been developed to inhibit factor XI(a). Many inhibitors are in early development and few have been evaluated in clinical trials.Expert opinion: Factor XI(a) is being actively pursued as a drug target for the development of effective and safer anticoagulants. Although many patents claiming factor XI(a) inhibitors were filed prior to 2016, recent literature reveals a moderately declining trend. Nevertheless, more agents have entered different levels of clinical trials. These agents exploit diverse mechanistic strategies for inhibition. Although further development is warranted, reaching one or more of these agents to the clinic will transform the anticoagulation therapy.
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Affiliation(s)
- Rami A Al-Horani
- Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, USA
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Prevalence and predictors of inappropriate apixaban dosing in patients with non-valvular atrial fibrillation at a large tertiary academic medical institution. DRUGS & THERAPY PERSPECTIVES 2019. [DOI: 10.1007/s40267-019-00696-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Schaffer AL, Falster MO, Brieger D, Jorm LR, Wilson A, Hay M, Leeb K, Pearson S, Nasis A. Evidence-Practice Gaps in Postdischarge Initiation With Oral Anticoagulants in Patients With Atrial Fibrillation. J Am Heart Assoc 2019; 8:e014287. [PMID: 31795822 PMCID: PMC6951075 DOI: 10.1161/jaha.119.014287] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Background Oral anticoagulant (OAC) therapy reduces the risk of stroke in people with atrial fibrillation (AF), and is considered best practice; however, there is little Australian evidence around the uptake of OACs in this population. Methods and Results We used linked hospital admissions, pharmaceutical dispensing claims, medical services, and mortality data for people in Australia's 2 most populous states (July 2010 to June 2015). Among OAC‐naïve people hospitalized with AF, we estimated initiation of OAC therapy within 30 days of discharge, and persistence with therapy in the first year. We analyzed both outcomes using multivariable Cox regression. In 71 184 people with AF (median age 78 years, 49% female), 22.7% initiated OAC therapy. Initiation was lowest in July to December 2011 (17.0%) and highest in July to December 2014 (30.1%) after subsidy of the direct OACs. In adjusted analyses, initiation was most likely in people with a CHA2DS2‐VA score ≥7 (versus 0) (hazard ratio=6.25, 95% CI 5.08–7.69), and a history of venous thromboembolism (hazard ratio=2.65, 95% CI 2.49–2.83). Of the people who initiated OAC therapy, 39.9% discontinued within 1 year; a lower risk of discontinuation was associated with a CHA2DS2‐VA score ≥7 (versus 0) (hazard ratio=0.22, 95% CI 0.14–0.35), or initiation on a direct OAC (versus warfarin) (hazard ratio=0.55, 95% CI 0.50–0.60). Conclusions We found that OAC therapy was severely underutilized in people hospitalized with AF, even among high‐risk individuals. Reasons for this underuse, whether patient, prescriber, or hospital related, should be identified and addressed to reduce stroke‐related morbidity and mortality in people with AF.
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Affiliation(s)
| | | | - David Brieger
- Cardiac Clinical Network Agency for Clinical Innovation Chatswood Australia
| | - Louisa R Jorm
- Centre for Big Data Research in Health UNSW Sydney Sydney Australia
| | | | - Melanie Hay
- Victorian Agency for Health Information Melbourne Australia
| | - Kira Leeb
- Victorian Agency for Health Information Melbourne Australia
| | - Sallie Pearson
- Centre for Big Data Research in Health UNSW Sydney Sydney Australia.,Menzies Centre for Health Policy Charles Perkins Centre The University of Sydney Australia
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Staerk L, Fosbøl EL, Lamberts M, Bonde AN, Gadsbøll K, Sindet-Pedersen C, Holm EA, Gerds TA, Ozenne B, Lip GYH, Torp-Pedersen C, Gislason GH, Olesen JB. Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study. Eur Heart J 2019; 39:1698-1705a. [PMID: 29165556 DOI: 10.1093/eurheartj/ehx598] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 10/02/2017] [Indexed: 11/14/2022] Open
Abstract
Aims We examined the risks of all-cause mortality, stroke, major bleeding, and recurrent traumatic injury associated with resumption of vitamin K antagonists (VKAs) and non-VKAs oral anticoagulants (NOACs) following traumatic injury in atrial fibrillation (AF) patients. Methods and results This was a Danish nationwide registry-based study (2005-16), including 4541 oral anticoagulant (OAC)-treated AF patients experiencing traumatic injury (defined as traumatic brain injury, hip fracture, or traumatic torso or abdominal injury). Within 90 days following discharge from traumatic injury, 60.6% resumed VKA (median age = 80, CHA2DS2-VASc = 4, HAS-BLED = 2), 16.7% resumed NOAC (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 2), and 22.7% did not resume OAC treatment (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 3). Switch from VKA to NOAC occurred among 9.5%. Since 2009, the trend in OAC resumption increased (P-value <0.0001), in particular with NOACs (P-value <0.0001). Follow-up started 90 days after discharge, and time-varying multiple Cox regression analyses were used for comparisons. Compared with non-resumption, VKA and NOAC resumption were associated with lower hazard [95% confidence interval (CI)] of all-cause mortality [hazard ratio (HR) 0.48 (0.42-0.53) and HR 0.55 (0.47-0.66), respectively] and ischaemic stroke [HR 0.56 (0.43-0.72) and HR 0.54 (0.35-0.82), respectively], increased major bleeding hazard [HR 1.30 (1.03-1.64) and HR 1.15 (0.81-1.63), respectively], and similar hazard of recurrent traumatic injury [HR 0.93 (0.73-1.18) and HR 0.87 (0.60-1.27), respectively]. Conclusion AF patients resuming VKA and NOAC treatment following traumatic injury have lower hazard of all-cause mortality and ischaemic stroke, increased hazard of major bleeding but without additional hazards of recurrent traumatic injury. Withholding OAC following a traumatic injury in AF patients may not be warranted.
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Affiliation(s)
- Laila Staerk
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark
| | - Emil Loldrup Fosbøl
- Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.,The Danish Heart Association, Vognmagergade 7, 1120 Copenhagen K, Denmark
| | - Morten Lamberts
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark.,Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
| | - Anders Nissen Bonde
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark
| | - Kasper Gadsbøll
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark
| | - Caroline Sindet-Pedersen
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark
| | - Ellen A Holm
- Department of Internal Medicine, Nykøbing F. Hospital, Fjordvej 15, 4800 Nykøbing Falster, Denmark
| | - Thomas Alexander Gerds
- Department of Public Health, Section of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, 1353 Copenhagen K, Denmark
| | - Brice Ozenne
- Department of Public Health, Section of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, 1353 Copenhagen K, Denmark
| | - Gregory Y H Lip
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham B15 2TT, UK.,Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Fredrik Bajers vej 5, 9100 Aalborg, Denmark
| | - Christian Torp-Pedersen
- Department of Cardiology and Clinical Epidemiology, Aalborg University Hospital, Hobrovej 18-22, 9100 Aalborg, Denmark.,Department of Health, Science and Technology, Aalborg University, Fredrik Bajers vej 5, 9100 Aalborg, Denmark
| | - Gunnar Hilmar Gislason
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark.,The Danish Heart Association, Vognmagergade 7, 1120 Copenhagen K, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.,The National Institute of Public Health, University of Southern Denmark, Øster Farimagsgade 5, 1353 Copenhagen K, Denmark
| | - Jonas Bjerring Olesen
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark
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Abstract
Recent advances in our understanding of the contribution of thrombin generation to arterial thrombosis and the role of platelets in venous thrombosis have prompted new treatment paradigms. Nonetheless, bleeding remains the major side effect of such treatments spurring the quest for new antithrombotic regimens with better benefit-risk profiles and for safer anticoagulants for existing and new indications. The aims of this article are to review the results of recent trials aimed at enhancing the benefit-risk profile of antithrombotic therapy and explain how these findings are changing our approach to the management of arterial and venous thrombosis. Focusing on these 2 aspects of thrombosis management, this article discusses 4 advances: (1) the observation that in some indications, lowering the dose of some direct oral anticoagulants reduces the risk of bleeding without compromising efficacy, (2) the recognition that aspirin is not only effective for secondary prevention of atherothrombosis but also for prevention of venous thromboembolism, (3) the finding that dual pathway inhibition with the combination of low-dose rivaroxaban to attenuate thrombin generation plus aspirin to reduce thromboxane A2-mediated platelet activation is superior to aspirin or rivaroxaban alone for prevention of atherothrombosis in patients with coronary or peripheral artery disease, and (4) the development of inhibitors of factor XI or XII as potentially safer anticoagulants.
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Affiliation(s)
- Noel C Chan
- From the Thrombosis and Atherosclerosis Research Institute and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Jeffrey I Weitz
- From the Thrombosis and Atherosclerosis Research Institute and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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Shum P, Klammer G, Toews D, Barry A. Anticoagulant Utilization and Direct Oral Anticoagulant Prescribing in Patients with Nonvalvular Atrial Fibrillation. Can J Hosp Pharm 2019; 72:428-434. [PMID: 31853143 PMCID: PMC6910852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
BACKGROUND Direct oral anticoagulants (DOACs) are indicated for prevention of stroke and embolism in patients with nonvalvular atrial fibrillation (NVAF). These agents have been shown to be non-inferior to warfarin in terms of efficacy and safety. However, their uptake in practice has been variable, and prescribed dosages may be inconsistent with manufacturer recommendations. OBJECTIVES To evaluate patterns of oral anticoagulant use in patients with NVAF, including determination of patient characteristics associated with the prescribing of warfarin or DOACs and whether prescribed dosages of DOACs were concordant with manufacturer recommendations. METHODS This retrospective chart review was conducted from April to September 2017 at Abbotsford Regional Hospital, Abbotsford, British Columbia. Patients at least 18 years of age with NVAF and CHADS-65 score of 1 or higher were included. Patients with contraindications to oral anticoagulants, those with reversible atrial fibrillation, and those undergoing renal dialysis were excluded. The dosage of DOACs was categorized as too low, too high, or correct in relation to manufacturer recommendations for the Canadian product. RESULTS A total of 120 patients were included. At discharge, 83 (69%) of the patients had a prescription for DOAC, 25 (21%) had a prescription for warfarin, and 12 (10%) had no prescription for an oral anticoagulant. There were no statistically significant differences between the warfarin and DOAC groups with respect to patient characteristics. Among the 56 patients for whom a full DOAC dose was indicated, 7 (13%) received a dose that was too low. Among the 23 patients for whom a full DOAC dose was not indicated, 4 (17%) received a dose that was too high. CONCLUSIONS At the study hospital, most patients with NVAF and CHADS-65 score of at least 1 had a discharge prescription for DOAC. Patient characteristics appeared to be similar between the warfarin and DOAC groups. For a notable proportion of patients who received a DOAC, the dosage was incorrect. Appropriate prescribing of oral anticoagulants could be further improved by education for prescribers and involvement of hospital pharmacists.
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Affiliation(s)
- Priscilla Shum
- , BSc(Pharm), ACPR, is with the Peace Arch Hospital, Fraser Health Authority, White Rock, British Columbia
| | - Gordon Klammer
- , BSc(Pharm), ACPR, BCPS, is with Lower Mainland Pharmacy Services, Abbotsford, British Columbia
| | - Dale Toews
- , BSc(Pharm), ACPR, is with Lower Mainland Pharmacy Services, Abbotsford, British Columbia
| | - Arden Barry
- , BSc, BSc(Pharm), ACPR, PharmD, is with Lower Mainland Pharmacy Services, Abbotsford, British Columbia, and The University of British Columbia, Vancouver, British Columbia
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Leiter MR, Packard KA, Qi Y, Krueger SK. Improved Dosing and Administration of Rivaroxaban when Prescribed by a Cardiologist. Heart Int 2019; 13:24-27. [PMID: 36275502 PMCID: PMC9562422 DOI: 10.17925/hi.2019.13.1.24] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 10/04/2018] [Indexed: 12/06/2023] Open
Abstract
UNLABELLED Rivaroxaban is a direct oral anticoagulant (DOAC) indicated to reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). A discrepancy exists between the recommended dosage and real-world use of DOACs, especially rivaroxaban, thus putting patients at risk of thromboembolic events. METHODS This retrospective study assessed real-world prescribing and patient adherence to dietary requirements during use of rivaroxaban in 116 patients with AF. Associations between prescriber specialty and the correct dosing and administration were assessed using the Chi-Square test. RESULTS Most rivaroxaban prescriptions were ordered by cardiologists (50.9%). Sixty-nine patients (59.5%) were taking the right dose at the correct time with an adequate meal. Of the 47 (40.5%) taking rivaroxaban incorrectly, 39 (33.6%) had not been administered an adequate meal and eight (6.9%) were not prescribed the correct dose. Compared with other prescribers, patients were most likely to be taking the correct dose and administration when prescribed by cardiologists (72.9% versus 45.6%; p=0.003). Patients were least likely to be taking the correct dose and administration when prescribed by primary care providers (44.4% versus 69.0%; p=0.009). This difference was driven by patients who did not take the treatment with an adequate meal. CONCLUSION Inappropriate prescribing, administration and non-adherence to DOACs can have devastating consequences. This highlights the importance of formal systematic education of patients prescribed DOACs across the whole health system. Future studies are warranted to explore the impact of non-adherence to rivaroxaban dietary requirements on clinical outcomes.
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Affiliation(s)
- Madeline R Leiter
- Creighton University, School of Pharmacy and Health Professions, Omaha, NE, USA
| | - Kathleen A Packard
- Creighton University, School of Pharmacy and Health Professions, Omaha, NE, USA
- Bryan Health Medical Center, Bryan Heart Institute, Lincoln, NE, USA
| | - Yongyue Qi
- Creighton University, School of Pharmacy and Health Professions, Omaha, NE, USA
| | - Steven K Krueger
- Bryan Health Medical Center, Bryan Heart Institute, Lincoln, NE, USA
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Loukianov MM, Martsevich SY, Drapkina OM, Yakushin SS, Vorobyev AN, Pereverzeva KG, Zagrebelnyy AV, Yakusevich VV, Yakusevich VV, Pozdnyakova EM, Gomova TA, Fedotova EE, Valiakhmetov MN, Mikhin VP, Maslennikova YV, Andreenko EY, Klyashtorny VG, Kudryashov EV, Okshina EY, Panagopulu MA, Boytsov SA. The Therapy with Oral Anticoagulants in Patients with Atrial Fibrillation in Outpatient and Hospital Settings (Data from RECVASA Registries). RATIONAL PHARMACOTHERAPY IN CARDIOLOGY 2019. [DOI: 10.20996/1819-6446-2019-15-4-538-545] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Aim. To evaluate an incidence of oral anticoagulants (OAC) administration during longterm follow-up period in patients with atrial fibrillation (AF) enrolled in outpatient and hospital RECVASA registries.Material and methods. 3169 patients with AF were enrolled in outpatient registries RECVASA (Ryazan), RECVASA AF-Yaroslavl and hospital registries RECVASA AF (Moscow, Kursk, Tula), age 70.9±10.7 years, 43.1% men. The incidence of OAC administration was evaluated in hospital and outpatient settings, including longterm follow-up period (2-6 years).Results. OAC were administrated only in 42.2% of cases (1335 from 3169 patients; age 69.1±10.4 years, 43% men), including warfarin (817 patients; 26%) and non-vitamin K antagonist oral anticoagulants (NOAC) – 518 (16%). Patients with permanent and persistant types of AF had lower incidence of OAC administration (43% and 40%) than in cases of paroxysmal type (47.6%, p<0.05), despite of the higher СНА2DS2-VASc risk score (4.69±1.66 and 4.23±1.57 vs 3.81±1.69; р<0.05). Patients with and without history of stroke received OAC in 42.5% and 40% of cases that means no significant difference (p>0.05) contrary to the pronounced difference of thromboembolic risk in these groups (6.14±1.34 and 3.77±1.39; р<0.001). The incidence of OAC administration in hospitals (54.1%) was 2.3 times higher than before hospitalization (23.8%) and was 4.1 times higher than in outpatient registries (13.5%). During follow-up period after hospital treatment (2.3±0.9 years) this parameter decreased from 54.1% to 41.2%, but was still 1.8 times higher than before admission to the hospital. After 4 years follow-up in RECVASA (Ryazan) registry we revealed 4.4 times higher incidence of OAC administration compared with enrollment data (4.2% and 18.3%, р<0.0001). This data was confirmed by the information from outpatient medical cards of accidentally generated group (75 from 297 patients survived during follow-up period): 5.3% at baseline and 22.7% six years later.Conclusions. RECVASA registries in 5 regions of Russia revealed low incidence of OAC administration. The risk of thromboembolic events was higher in patients with AF and no OAC administration compared with patients who received OAC. Patients with paroxysmal type of AF received OAC more often than those with permanent type. There were no significant differences of incidence of OAC therapy in patients with and without history of stroke. Both questioning of patients with AF and analysis of medical cards in outpatient clinics revealed higher incidence of OAC administration after 4-6 years of follow-up compared with the stage of enrollment in registries.
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Affiliation(s)
| | | | - O. M. Drapkina
- National Medical Research Center for Preventive Medicine
| | - S. S. Yakushin
- Ryazan State Medical University named after Academician I.P. Pavlov
| | - A. N. Vorobyev
- Ryazan State Medical University named after Academician I.P. Pavlov
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - E. Yu. Okshina
- National Medical Research Center for Preventive Medicine
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Lin YC, Chien SC, Hsieh YC, Shih CM, Lin FY, Tsao NW, Chen CW, Kao YT, Chiang KH, Chen WT, Chien LN, Huang CY. Effectiveness and Safety of Standard- and Low-Dose Rivaroxaban in Asians With Atrial Fibrillation. J Am Coll Cardiol 2019; 72:477-485. [PMID: 30049307 DOI: 10.1016/j.jacc.2018.04.084] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 04/24/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND Low-dose rivaroxaban (10 mg/day) has been widely used in Asia for patients with atrial fibrillation (AF), although there is a lack of evidence regarding its effectiveness. In Asians, it is unclear whether low-dose rivaroxaban is equally effective as that of the standard dose or is associated with less bleeding risk. OBJECTIVES The aim of this study was to evaluate the effectiveness and safety of standard-dose (15 or 20 mg/day) and low-dose (10 mg/day) rivaroxaban in Asians with AF. METHODS Using data files from the National Health Insurance Research Database between May 1, 2014, and September 30, 2015, a retrospective population-based cohort study was conducted in patients diagnosed with AF or atrial flutter and treated with low- or standard-dose rivaroxaban. Patients were followed up until the first occurrence of the study outcome or the end of the observation period (December 31, 2015). RESULTS Among 6,558 eligible patients, a total of 2,373 and 4,185 patients took low- and standard-dose rivaroxaban, respectively. Compared to standard-dose rivaroxaban, low-dose rivaroxaban was associated with a significantly higher risk of myocardial infarction (subdistribution hazard ratio: 2.26; 95% confidence interval: 1.13 to 4.52), with similar risk of ischemic stroke, systemic embolism, major bleeding, and nonmajor clinically relevant bleeding. CONCLUSIONS Compared to standard-dose rivaroxaban, low-dose rivaroxaban in Asian patients with AF was associated with similar risks of thromboembolism and bleeding except myocardial infarction.
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Affiliation(s)
- Yi-Cheng Lin
- Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan
| | - Shu-Chen Chien
- Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Yi-Chen Hsieh
- PhD Program of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; PhD Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program in Applied Molecular Epidemiology, College of Public Health, Taipei Medical University, Taipei, Taiwan
| | - Chun-Ming Shih
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Feng-Yen Lin
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Nai-Wen Tsao
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chih-Wei Chen
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yung-Ta Kao
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Kuang-Hsing Chiang
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
| | - Wan-Ting Chen
- Health and Clinical Research Data Center, College of Public Health, Taipei Medical University, Taipei, Taiwan
| | - Li-Nien Chien
- School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan.
| | - Chun-Yao Huang
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
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46
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Fastner C, Nienaber CA, Park JW, Brachmann J, Zeymer U, Goedde M, Sievert H, Geist V, Lewalter T, Krapivsky A, Käunicke M, Maier J, Özdemir B, Hochadel M, Schneider S, Senges J, Akin I. Impact of left atrial appendage morphology on indication and procedural outcome after interventional occlusion: results from the prospective multicentre German LAARGE registry. EUROINTERVENTION 2019; 14:151-157. [PMID: 29508766 DOI: 10.4244/eij-d-17-00866] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
AIMS Interventional left atrial appendage closure (LAAC) is an emerging alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) in concomitance with a contraindication for standard OAC. This sub-analysis of the LAARGE registry aimed to investigate differences between different LAA morphologies in a real-world setting. METHODS AND RESULTS This prospective, multicentre, observational registry included 562 patients from 37 centres with ineligibility for long-term OAC between April 2014 and January 2016. Baseline characteristics, indications, procedural data and complications were registered according to each LAA morphology (i.e., chicken wing, cauliflower, windsock, cactus and atypical morphologies). Implantation success was high across the four typical anatomies (≥97.5%, p=n.s.); only atypical anatomies exhibited a lower success rate (94%). The cactus-shaped LAA was linked to a trend indicating a shorter fluoroscopy time, while the atypical LAA was linked to a significantly prolonged fluoroscopy time (p=0.089 and p=0.025 versus the overall mean, respectively). Periprocedural and intra-hospital complications were generally rare, with no differences among the different morphologies (p=n.s.). CONCLUSIONS Procedural success as well as the complication rates of LAAC were not different among the four typical LAA morphologies. A lower implantation success rate was only obvious in patients with atypical LAA morphologies.
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Affiliation(s)
- Christian Fastner
- First Department of Medicine, University Medical Center Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) partner site Heidelberg/Mannheim, University of Heidelberg, Mannheim, Germany
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Hernandez I, He M, Chen N, Brooks MM, Saba S, Gellad WF. Trajectories of Oral Anticoagulation Adherence Among Medicare Beneficiaries Newly Diagnosed With Atrial Fibrillation. J Am Heart Assoc 2019; 8:e011427. [PMID: 31189392 PMCID: PMC6645643 DOI: 10.1161/jaha.118.011427] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Only 50% of atrial fibrillation (AF) patients recommended for oral anticoagulation (OAC) use these medications, and less than half of them adhere to OAC. In a cohort of Medicare beneficiaries newly diagnosed with AF, we identified groups of patients with similar trajectories of OAC use and adherence, and evaluated patient characteristics affecting group membership. Methods and Results We selected continuously enrolled Medicare Part D beneficiaries with first AF diagnosis in 2014 to 2015 (n=34 898). We calculated the proportion of days covered with OAC over the first 12 months after diagnosis and identified OAC adherence trajectories using group‐based trajectory models. We constructed multinomial logistic regression models to evaluate how demographics, system‐level factors, and clinical characteristics were associated with group membership. We identified 4 trajectories of OAC adherence: patients who never used OAC (43.8%), late OAC initiators (7.6%), early OAC discontinuers (8.9%), and continuously adherent patients (40.1%). Predictors such as sex, black race, residence in the South, or HAS‐BLED score were associated with not only OAC use, but also the timing of initiation and the likelihood of discontinuation. For example, HAS‐BLED score ≥4 was associated with a higher likelihood of not using OAC (odds ratio 1.35; 95% CI, 1.14–1.62), of late initiation (1.55; 95% CI, 1.11–2.05), and of early discontinuation (odds ratio 1.35; 95% CI, 1.01–1.84). Conclusions We identified 4 distinct trajectories of OAC adherence after first AF diagnosis, with <45% of newly diagnosed AF patients belonging to the trajectory group characterized by continuous OAC adherence. Trajectories were associated not only with demographic and clinical characteristics but also with regional factors.
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Affiliation(s)
- Inmaculada Hernandez
- 1 Department of Pharmacy and Therapeutics School of Pharmacy University of Pittsburgh PA
| | - Meiqi He
- 1 Department of Pharmacy and Therapeutics School of Pharmacy University of Pittsburgh PA
| | - Nemin Chen
- 1 Department of Pharmacy and Therapeutics School of Pharmacy University of Pittsburgh PA.,2 Department of Epidemiology Graduate School of Public Health University of Pittsburgh PA
| | - Maria M Brooks
- 2 Department of Epidemiology Graduate School of Public Health University of Pittsburgh PA
| | - Samir Saba
- 3 Heart and Vascular Institute University of Pittsburgh Medical Centre Pittsburgh PA
| | - Walid F Gellad
- 4 Department of General Internal Medicine School of Medicine University of Pittsburgh PA.,5 VA Pittsburgh Healthcare System Pittsburgh PA
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Maura G, Billionnet C, Drouin J, Weill A, Neumann A, Pariente A. Oral anticoagulation therapy use in patients with atrial fibrillation after the introduction of non-vitamin K antagonist oral anticoagulants: findings from the French healthcare databases, 2011-2016. BMJ Open 2019; 9:e026645. [PMID: 31005934 PMCID: PMC6500377 DOI: 10.1136/bmjopen-2018-026645] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVES To describe (i) the trend in oral anticoagulant (OAC) use following the introduction of non-vitamin K antagonist oral anticoagulant (NOAC) therapy for stroke prevention in atrial fibrillation (AF) patients and (ii) the current patterns of use of NOAC therapy in new users with AF in France. DESIGN (i) Repeated cross-sectional study and (ii) population-based cohort study. SETTING French national healthcare databases (50 million beneficiaries). PARTICIPANTS (i) Patients with identified AF in 2011, 2013 and 2016 and (ii) patients with AF initiating OAC therapy in 2015-2016. PRIMARY AND SECONDARY OUTCOME MEASURES: (i) Trend in OAC therapy use in patients with AF and (ii) patterns of use of NOAC therapy in new users with AF. RESULTS Between 2011 and 2016, use of OAC therapy moderately increased (+16%), while use of antiplatelet therapy decreased (-22%) among all patients with identified AF. In 2016, among the 1.1 million AF patients, 66% used OAC therapy and were more likely to be treated by vitamin K antagonist (VKA) than NOAC therapy, including patients at higher risk of stroke (63.5%), while 33% used antiplatelet therapy. Among 192 851 new users of OAC therapy in 2015-2016 with identified AF, NOAC therapy (66.3%) was initiated more frequently than VKA therapy, including in patients at higher risk of stroke (57.8%). Reduced doses were prescribed in 40% of NOAC new users. Several situations of inappropriate use at NOAC initiation were identified, including concomitant use of drugs increasing the risk of bleeding (one in three new users) and potential NOAC underdosing. CONCLUSIONS OAC therapy use in patients with AF remains suboptimal 4 years after the introduction of NOACs for stroke prevention in France and improvement in appropriate prescribing regarding NOAC initiation is needed. However, NOAC therapy is now the preferred drug class for initiation of OAC therapy in patients with AF, including in patients at higher risk of stroke.
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Affiliation(s)
- Géric Maura
- Department of Studies in Public Health, French National Health Insurance (Caisse Nationale de l’Assurance Maladie/Cnam), Paris, France
- University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology - UMR 1219, Bordeaux, France
| | - Cécile Billionnet
- Department of Studies in Public Health, French National Health Insurance (Caisse Nationale de l’Assurance Maladie/Cnam), Paris, France
| | - Jérôme Drouin
- Department of Studies in Public Health, French National Health Insurance (Caisse Nationale de l’Assurance Maladie/Cnam), Paris, France
| | - Alain Weill
- Department of Studies in Public Health, French National Health Insurance (Caisse Nationale de l’Assurance Maladie/Cnam), Paris, France
| | - Anke Neumann
- Department of Studies in Public Health, French National Health Insurance (Caisse Nationale de l’Assurance Maladie/Cnam), Paris, France
| | - Antoine Pariente
- University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology - UMR 1219, Bordeaux, France
- CHU Bordeaux, Bordeaux, France
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49
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How I manage anticoagulant therapy in older individuals with atrial fibrillation or venous thromboembolism. Blood 2019; 133:2269-2278. [PMID: 30926593 DOI: 10.1182/blood-2019-01-846048] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 03/26/2019] [Indexed: 01/08/2023] Open
Abstract
Anticoagulant therapy is the most effective strategy to prevent arterial and venous thromboembolism, but treating older individuals is challenging, because increasing age, comorbidities, and polypharmacy increase the risk of both thrombosis and bleeding. Warfarin and non-vitamin K antagonist oral anticoagulants are underused and often underdosed in the prevention of stroke in older patients with atrial fibrillation because of concerns about the risk of bleeding. Poor adherence to anticoagulant therapy is also an issue for older patients with atrial fibrillation and those at risk of recurrent pulmonary embolism. In this review, we present 5 clinical cases to illustrate common challenges with anticoagulant use in older patients and discuss our approach to institute safe and effective antithrombotic therapy.
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50
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Székely O, Borgi M, Lip GYH. Factor XI inhibition fulfilling the optimal expectations for ideal anticoagulation. Expert Opin Emerg Drugs 2019; 24:55-61. [DOI: 10.1080/14728214.2019.1591368] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Orsolya Székely
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Marco Borgi
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Gregory Y. H. Lip
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
- Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark
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