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Banach M, Jaiswal V, Ang SP, Sawhney A, Deb N, Amarenco P, Gaita D, Reiner Z, Pećin I, Lavie CJ, Penson PE, Toth PP. Impact of Lipid-Lowering Combination Therapy With Statins and Ezetimibe vs Statin Monotherapy on the Reduction of Cardiovascular Outcomes: A Meta-analysis. Mayo Clin Proc 2025:S0025-6196(25)00075-8. [PMID: 40126455 DOI: 10.1016/j.mayocp.2025.01.018] [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: 10/13/2024] [Revised: 01/06/2025] [Accepted: 01/28/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVE To evaluate the efficacy of combination lipid-lowering therapy (LLT) compared with statin monotherapy for low-density lipoprotein cholesterol (LDL-C) reduction, associated adverse events, and outcomes. METHODS A systematic literature search was conducted using PubMed, Embase, and ClinicalTrials.gov to identify relevant articles published from inception until the end of June 2024. The outcomes were assessed using pooled odds ratios (ORs) for categorical data and mean difference for continuous data, with corresponding 95% CIs. RESULTS A total of 14 studies (11 randomized controlled trials and 3 cohort studies) with 108,373 very high-risk patients were included in the final analysis. The mean age of the patients in the combination LLT group and the statin monotherapy group was 67.31 and 67.89 years, respectively. Pooled analysis revealed that combination LLT significantly more effectively reduced the LDL-C level from baseline (mean difference, -12.96 mg/dL; 95% CI, -17.27 to -8.65; P<.001) and significantly reduced all-cause mortality (OR, 0.81; 95% CI, 0.67 to 0.97; P=.02), major adverse cardiovascular events (OR, 0.82; 95% CI, 0.69 to 0.97; P=.02), and stroke incidence (OR, 0.83; 95% CI, 0.75 to 0.91; P<.001), with an insignificant effect on cardiovascular mortality (OR, 0.86; 95% CI, 0.65 to 1.12; P=.26) when compared with statin monotherapy. The risk of adverse events and the therapy discontinuation rate were comparable between groups. CONCLUSION Combination LLT was associated with an overall greater reduction in LDL-C, the same risk of adverse effects, and significantly lower risk of all-cause mortality, major adverse cardiovascular events, and stroke compared with statin monotherapy. Forthcoming guidelines should consider the lipid-lowering combination therapy as early as possible, preferably up-front, for more effective LDL-C goal achievement and significant reduction of cardiovascular disease outcomes and mortality in high- and very high-risk patients.
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Affiliation(s)
- Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland; Faculty of Medicine, John Paul II Catholic University of Lublin, Lublin, Poland; Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool, UK.
| | - Vikash Jaiswal
- Department of Cardiovascular Research, Larkin Community Hospital, South Miami, FL
| | - Song Peng Ang
- Department of Internal Medicine, Rutgers Health/Community Medical Center, Toms River, NJ
| | - Aanchal Sawhney
- Department of Internal Medicine, Crozer-Chester Medical Center, Upland, PA
| | - Novonil Deb
- North Bengal Medical College, West Bengal, India
| | - Pierre Amarenco
- Department of Neurology and Stroke Center, Bichat University Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Dan Gaita
- Institute for Cardiovascular Diseases, Research Center IBCVTIM, Timisoara, Romania
| | - Zeljko Reiner
- Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; University Hospital Center Zagreb, Zagreb, Croatia
| | - Ivan Pećin
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Carl J Lavie
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School-University of Queensland School of Medicine, New Orleans, LA
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University and Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Peter P Toth
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Preventive Cardiology, CGH Medical Center, Sterling, IL
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Jape D, He WB, Stub D, Nanayakkara S, Shaw JA. Ezetimibe Eligibility and Prescribing in Patients With Acute Coronary Syndrome. Heart Lung Circ 2025; 34:235-243. [PMID: 39904703 DOI: 10.1016/j.hlc.2024.12.009] [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: 07/23/2024] [Revised: 12/12/2024] [Accepted: 12/29/2024] [Indexed: 02/06/2025]
Abstract
BACKGROUND Ezetimibe is a safe and effective medication for achieving secondary prevention low-density lipoprotein-cholesterol (LDL-C) targets after acute coronary syndrome (ACS). We sought to examine ezetimibe prescribing after ACS and the effects of expanding the Australian Pharmaceutical Benefits Scheme eligibility criteria. METHOD A retrospective analysis was performed for the rates and factors of ezetimibe eligibility and prescribing in ezetimibe-naive patients with ACS admitted to a single quaternary centre between May 2020 and September 2022. Eligibility rates were also assessed with tighter LDL-C targets and with modelling to identify patients unlikely to achieve targets with first-line care. RESULTS Of 757 patients with ACS with LDL-C >1.8 mmol/L, 94 were eligible for ezetimibe. This subgroup was highly comorbid but only 16 patients were prescribed ezetimibe. The univariate logistic regression identified statin contraindication (odds ratio 19.4; 95% confidence interval 4.58-103.9; p<0.001) and higher LDL-C (odds ratio 2.43 per 1 mmol/L; 95% confidence interval 1.44-4.67; p=0.03) as key predictors of prescribing. Of 956 patients with ACS with an LDL-C >1.4 mmol/L, tightening LDL-C targets from 1.8 to 1.4 mmol/L increased eligibility from 94 (9.8%) to 152 (16.0%) patients, whereas predictive modelling substantially expanded eligibility to 309 (32.3%) and 620 (64.9%) with the 1.8 mmol/L and 1.4 mmol/L targets, respectively. CONCLUSIONS In the acute setting after ACS, Australian Pharmaceutical Benefits Scheme restrictions limit ezetimibe to highly comorbid patients with a high risk of recurrent disease. Despite this, the prescribing rates were poor. Furthermore, a larger group of patients are discharged on treatments that are unlikely to achieve guideline-directed LDL-C targets. Rationalising eligibility criteria for ezetimibe would likely improve access to early and effective secondary prevention.
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Affiliation(s)
- Dylan Jape
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia
| | - William B He
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia
| | - Dion Stub
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia; Baker Heart & Diabetes Institute, Melbourne, Vic, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic, Australia
| | - Shane Nanayakkara
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia; Baker Heart & Diabetes Institute, Melbourne, Vic, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic, Australia
| | - James A Shaw
- Department of Cardiology, Alfred Health, Melbourne, Vic, Australia; Baker Heart & Diabetes Institute, Melbourne, Vic, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic, Australia.
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Wierzbicki AS. Advances in the pharmacological management of hyperlipidemia through the use of combination therapies. Expert Opin Pharmacother 2025; 26:157-165. [PMID: 39709627 DOI: 10.1080/14656566.2024.2444986] [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: 09/16/2024] [Revised: 12/02/2024] [Accepted: 12/17/2024] [Indexed: 12/24/2024]
Abstract
INTRODUCTION Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies have been performed, but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them. AREAS COVERED Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a). Imaging studies have often shown benefits paralleling lipid studies. However, outcome studies have failed to show added benefits with niacin or fibrates while confirming the benefits of ezetimibe, bempedoic acid and proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors and icosapent ethyl. EXPERT OPINION Combination therapy for LDL-C in dual combinations is well validated. Data for intervention on triglycerides is limited to icosapent ethyl, but this may exert effects independent of lipids. New drugs targeting triglycerides through apolipoprotein C3 and angiopoietin-like peptides are in development. Studies on combination therapy raising HDL-C have generally disappointed, though cholesterol ester transfer protein (CETP) inhibition remains a target. Lipoprotein (a) is recognized as a CVD risk factor and effective therapies are in development but results on CVD events are lacking.
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Affiliation(s)
- Anthony S Wierzbicki
- Department of Metabolic Medicine/Chemical Pathology Guy's, St Thomas' Hospitals, London, UK
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Cha JJ, Hong SJ, Lim S, Kim JH, Joo HJ, Park JH, Yu CW, Lim DS, Kim JY, Jeong JO, Shin JH, Shim CY, Lee JY, Lim YH, Park SH, Cho EJ, Kim H, Lee J, Sung KC. Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults. Korean Circ J 2024; 54:534-544. [PMID: 38956936 PMCID: PMC11361771 DOI: 10.4070/kcj.2024.0036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 03/29/2024] [Accepted: 05/02/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. METHODS Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. RESULTS The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. CONCLUSIONS Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
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Affiliation(s)
- Jung-Joon Cha
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Soon Jun Hong
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
| | - Subin Lim
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Ju Hyeon Kim
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Hyung Joon Joo
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jae Hyoung Park
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Cheol Woong Yu
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Do-Sun Lim
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jang Young Kim
- Department of Cardiology, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea
| | - Jin-Ok Jeong
- Cardiovascular Center, Chungnam National University Hospital, Chungnam National University, Daejeon, Korea
| | - Jeong-Hun Shin
- Department of Cardiology, Hanyang University Guri Hospital, Guri, Korea
| | - Chi Young Shim
- Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong-Young Lee
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Hyo Lim
- Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Sung Ha Park
- Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Joo Cho
- Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hasung Kim
- Data Science Team, Hanmi Pharm. Co., Ltd, Seoul, Korea
| | - Jungkuk Lee
- Data Science Team, Hanmi Pharm. Co., Ltd, Seoul, Korea
| | - Ki-Chul Sung
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Leong CW, Yee KM, Rani TA, Lau KJ, Ahmad S, Amran A, Mohd Hassan FW, Kumar N. Pharmacokinetics and Bioequivalence of Fixed-Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open-Label Study in Healthy Volunteers. Clin Pharmacol Drug Dev 2024; 13:938-946. [PMID: 38745538 DOI: 10.1002/cpdd.1411] [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: 01/17/2024] [Accepted: 04/08/2024] [Indexed: 05/16/2024]
Abstract
The current study aimed to evaluate the bioequivalence of a new generic combination of simvastatin and ezetimibe with the reference formulation. An open-label, randomized, 3-period, 3-sequence, crossover study, including 60 healthy volunteers, was implemented. Participants received the test and reference formulation, each containing 20 mg of simvastatin and 10 mg of ezetimibe as a single-dose tablet, separated by a minimum of 2-week washout periods. Blood samples were collected for 20 time points from predose to 72 hours after the dose. The total ezetimibe assay was carried out using a validated liquid chromatography-tandem mass spectrometry, while unconjugated ezetimibe, simvastatin, and simvastatin β-hydroxy acid determination was done via a validated ultra-performance liquid chromatography-tandem mass spectrometry. Each assay was preceded by a liquid-liquid extraction step. The pharmacokinetic parameters were derived using noncompartmental analysis and then compared between the reference and test formulations via a multivariate analysis of variance. No statistical difference was found in under the concentration-time curve from time 0 to the last quantifiable concentration and maximum concentration of unconjugated ezetimibe, total ezetimibe, and simvastatin between the reference and test formulations. The 90% confidence intervals of unconjugated ezetimibe, total ezetimibe, and simvastatin natural log-transformed under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum concentration were in the range of 80%-125% as per the bioequivalence acceptance criteria. Therefore, the test formulation was bioequivalent to the reference formulation.
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Affiliation(s)
| | - Kar Ming Yee
- Duopharma Innovation Sdn. Bhd., Shah Alam, Selangor, Malaysia
| | - Tracy Ann Rani
- Duopharma Innovation Sdn. Bhd., Shah Alam, Selangor, Malaysia
| | - Kheng Jinm Lau
- Duopharma Innovation Sdn. Bhd., Shah Alam, Selangor, Malaysia
| | - Shahnun Ahmad
- Duopharma Innovation Sdn. Bhd., Shah Alam, Selangor, Malaysia
| | - Atiqah Amran
- Duopharma Innovation Sdn. Bhd., Shah Alam, Selangor, Malaysia
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Manolis AA, Manolis TA, Mikhailidis DP, Manolis AS. Are We Using Ezetimibe As Much As We Should? Biomark Insights 2024; 19:11772719241257410. [PMID: 38827240 PMCID: PMC11143858 DOI: 10.1177/11772719241257410] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 05/09/2024] [Indexed: 06/04/2024] Open
Abstract
Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance.
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Affiliation(s)
| | | | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK
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Velidakis N, Stachteas P, Gkougkoudi E, Papadopoulos C, Kadoglou NPE. Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease-A Narrative Clinical Review. Pharmaceuticals (Basel) 2024; 17:568. [PMID: 38794138 PMCID: PMC11124492 DOI: 10.3390/ph17050568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/26/2024] Open
Abstract
Diabetic atherosclerosis is a complex process that is characterized by diffuse and unstable lesions increasing 2-4-fold the risk of adverse cardiovascular (CV) events. Diabetic dyslipidemia has a predominant role in coronary artery disease (CAD) and has been the target of classical and emerging pharmaceutical agents with established or promising CV benefits. The aim of the present narrative review was to summarize the effects of classical and novel lipid-lowering pharmaceutical agents on lipid profile and CV outcomes in diabetic patients with established CAD or high risk of CAD. Statins remain the first-line treatment for all diabetic patients since they considerably ameliorate lipid parameters and non-lipid CV risk factors, leading to reduced CV morbidity and mortality. Complementary to statins, ezetimibe exerts lipid-lowering properties with modest but significant reductions in major adverse cardiovascular events (MACEs) and CV mortality. PCSK9 inhibitors considerably reduce LDL-C levels and lower MACEs in diabetic patients. On the other hand, fibrates may confer a very modest decline in MACE incidence, while the CV impact of omega-3 fatty acids is promising but remains questionable. Bempedoic acid and inclisiran have a potential therapeutic role in the management of diabetic dyslipidemia, but this is still not adequately documented. Given the heightened CV risk among individuals with diabetes, more decisive results would be of great importance in the utility of all these drugs.
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Affiliation(s)
- Nikolaos Velidakis
- Medical School, University of Cyprus, 2029 Nicosia, Cyprus; (N.V.); (E.G.)
| | - Panagiotis Stachteas
- Third Department of Cardiology, Aristotle University of Thessaloniki, General Hospital “Hippokration”, 541 24 Thessaloniki, Greece; (P.S.); (C.P.)
| | | | - Christodoulos Papadopoulos
- Third Department of Cardiology, Aristotle University of Thessaloniki, General Hospital “Hippokration”, 541 24 Thessaloniki, Greece; (P.S.); (C.P.)
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Caklili OT, Rizzo M, Cesur M. Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update. Curr Vasc Pharmacol 2024; 22:242-250. [PMID: 38323615 DOI: 10.2174/0115701611290763240126045433] [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: 11/04/2023] [Revised: 12/24/2023] [Accepted: 01/08/2024] [Indexed: 02/08/2024]
Abstract
Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.
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Affiliation(s)
- Ozge Telci Caklili
- Department of Endocrinology and Metabolism, Kocaeli City Hospital, Kocaeli, Türkiye
| | - Manfredi Rizzo
- School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Palermo, Italy
- College of Medicine, Mohammed Bin Rashid University (MBRU), Dubai, UAE
| | - Mustafa Cesur
- Department of Endocrinology and Metabolism, Ankara Guven Hospital, Ankara, Türkiye
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Farnier M, Santos RD, Cosin-Sales J, Ezhov MV, Liu J, Granados D, Santoni S, Khan I, Catapano AL. Projected impact of treatment intensification with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination on MACE across six countries. Eur J Prev Cardiol 2022; 29:2264-2271. [PMID: 36134461 DOI: 10.1093/eurjpc/zwac214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 08/08/2022] [Accepted: 09/14/2022] [Indexed: 01/11/2023]
Abstract
AIMS The 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidaemia guidelines recommend achievement of low-density lipoprotein cholestrol (LDL-C) goals based on an individual's risk. We aimed to evaluate the impact of guideline adoption with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination (FDC) on LDL-C goal achievement and incidence of major adverse cardiovascular events (MACE) across six countries. METHODS AND RESULTS A simulation model with a five-year horizon (2020-2024) was developed based on Institute for Health Metrics and Evaluation Global Burden of Disease Study database with a business-as-usual (BAU) scenario representing status quo, intervention scenario-1 representing treatment with statin and ezetimibe as separate agents, and intervention scenario-2 representing treatment with statin or statin plus ezetimibe FDC. MACE was defined as the composite of myocardial infarction, ischaemic stroke, and cardiovascular death. The mean population LDL-C was reduced from 4.25 mmol/L in the BAU scenario, to 3.65 mmol/L and 3.59 mmol/L in intervention scenarios-1 and -2, respectively. Compared with BAU, intervention scenarios-1 and-2 resulted in relative reduction of MACE by 5.4% and 6.4% representing ∼3.7 and 4.4 million MACE averted, respectively, across six countries over 5 years. The absolute benefit in terms of MACE averted was highest for China, whereas France had highest relative reduction in MACE with both intervention scenarios compared with BAU. CONCLUSION The 2019 ESC/EAS guideline-based treatment intensification with strategies based on statin, ezetimibe, and statin plus ezetimibe FDC is estimated to result in a substantial population-level benefit in terms of MACE averted compared with BAU.
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Affiliation(s)
- Michel Farnier
- Equipe PEC2, EA 7460, Service de Cardiologie, CHU Dijon Bourgogne, Université de Bourgogne Franche-Comté, 21000 Dijon, France
| | - Raul D Santos
- Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, Av. Dr Enéas C. Aguiar 44, 05403-900 São Paulo, Brazil.,Hospital Israelita Albert Einstein, Av. Albert Einstein, 627/701, 05652- 900, São Paulo, Brazil
| | - Juan Cosin-Sales
- Department of Cardiology, Hospital Arnau de Vilanova, Calle San Clemente 12, 46015 Valencia, Spain.,Departamento de Medicina, Facultad de Ciencias de la Salud, Universidad CEU-Cardenal Herrena, 46113 Moncada, Valencia, Spain
| | - Marat V Ezhov
- Laboratory of Lipid Disorders, Department of Atherosclerosis, A.L. Myasnikov Institute of Clinical Cardiology, National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, 15A, 3rd Cherepkovskaya street, Moscow 121552, Russia
| | - Jian Liu
- Department of Cardiology, Peking University People's Hospital, 11 Xizhimen South Street, 100044 Beijing, China
| | - Denis Granados
- Epidemiology and Benefit-Risk, Research and Development, Sanofi, 1, Avenue Pierre Brossolette, 91380 Chilly-Mazarin, France
| | - Serena Santoni
- Institute for Health Metrics and Evaluation, Population Health Building/Hans Rosling Center, 3980 15th Ave. NE, Seattle, WA 98195, USA
| | - Irfan Khan
- Medical Evidence Generation, General Medicines, Sanofi, Bridgewater, NJ 08807, USA
| | - Alberico L Catapano
- Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Via Balzaretti 9, 20133, Milan, Italy
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10
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Izar MCDO, Giraldez VZR, Bertolami A, Santos Filho RDD, Lottenberg AM, Assad MHV, Saraiva JFK, Chacra APM, Martinez TLR, Bahia LR, Fonseca FAH, Faludi AA, Sposito AC, Chagas ACP, Jannes CE, Amaral CK, Araújo DBD, Cintra DE, Coutinho EDR, Cesena F, Xavier HT, Mota ICP, Giuliano IDCB, Faria Neto JR, Kato JT, Bertolami MC, Miname MH, Castelo MHCG, Lavrador MSF, Machado RM, Souza PGD, Alves RJ, Machado VA, Salgado Filho W. Update of the Brazilian Guideline for Familial Hypercholesterolemia - 2021. Arq Bras Cardiol 2021; 117:782-844. [PMID: 34709306 PMCID: PMC8528358 DOI: 10.36660/abc.20210788] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
| | - Viviane Zorzanelli Rocha Giraldez
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
- Grupo Fleury, São Paulo, SP - Brasil
| | | | | | - Ana Maria Lottenberg
- Hospital Israelita Albert Einstein (HIAE) - Faculdade Israelita de Ciências da Saúde Albert Einstein (FICSAE), São Paulo, SP - Brasil
- Faculdade de Medicina da Universidade de São Paulo, Laboratório de Lípides (LIM10), São Paulo, São Paulo, SP - Brasil
| | | | | | - Ana Paula M Chacra
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
| | | | | | | | | | - Andrei C Sposito
- Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brasil
| | | | - Cinthia Elim Jannes
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
| | | | | | | | | | - Fernando Cesena
- Hospital Israelita Albert Einstein (HIAE), São Paulo, SP - Brasil
| | | | | | | | | | | | | | - Marcio Hiroshi Miname
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
| | - Maria Helane Costa Gurgel Castelo
- Universidade Federal do Ceará (UFC), Fortaleza, CE - Brasil
- Hospital do Coração de Messejana, Fortaleza, CE - Brasil
- Professora da Faculdade Unichristus, Fortaleza, CE - Brasil
| | - Maria Sílvia Ferrari Lavrador
- Hospital Israelita Albert Einstein (HIAE) - Faculdade Israelita de Ciências da Saúde Albert Einstein (FICSAE), São Paulo, SP - Brasil
| | - Roberta Marcondes Machado
- Faculdade de Medicina da Universidade de São Paulo, Laboratório de Lípides (LIM10), São Paulo, São Paulo, SP - Brasil
| | - Patrícia Guedes de Souza
- Hospital Universitário Professor Edgard Santos da Universidade Federal da Bahia (UFBA), Salvador, BA - Brasil
| | | | | | - Wilson Salgado Filho
- Instituto do Coração (InCor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
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11
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Sun C, Zheng W, Liang L, Liu Z, Sun W, Tang R. Ezetimibe Improves Rosuvastatin Effects on Inflammation and Vascular Endothelial Function in Acute Coronary Syndrome Patients Undergoing PCI. J Interv Cardiol 2021; 2021:2995602. [PMID: 34566523 PMCID: PMC8443370 DOI: 10.1155/2021/2995602] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 07/26/2021] [Accepted: 08/18/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Little is known of the acute effects of ezetimibe in patients with acute coronary syndrome (ACS) undergoing PCI. We investigated whether ezetimibe improves inflammation and vascular endothelial function in patients with ACS undergoing PCI. METHODS We randomized 171 patients with ACS undergoing PCI to receive ezetimibe 10 mg/day plus rosuvastatin 20 mg/day (combination group, n = 81) versus rosuvastatin 20 mg/day (rosuvastatin group, n = 90). Lipid profile, type II secretory phospholipase A2 (sPLA2-IIa), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were measured at baseline and after 7 days. Three months after PCI, clinical outcomes were examined. RESULT The levels of sPLA2-IIa and IL-1β reduced significantly in both groups, but more when ezetimibe and rosuvastatin were coadministered (sPLA2-IIa: 6.16 ± 2.67 vs. 7.42 ± 3.53 ng/ml, p=0.01; IL-1β: 37.39 ± 26.25 vs. 48.98 ± 32.26 pg/ml, p=0.01). A significant rise of VCAM-1 and ICAM-1 was observed on day 7 after PCI in the both groups, but was less in the combination group (VCAM-1: 918.28 ± 235.31 vs. 988.54 ± 194.41 ng/ml, p=0.03; ICAM-1: 213.01 ± 100.15 vs. 246.88 ± 105.71 ng/ml, p=0.03). Patients in the combination versus rosuvastatin group appeared to suffer from less major adverse events. Periprocedural therapy of ezetimibe improves rosuvastatin effects on proinflammatory responses and endothelial function associated with ACS patients undergoing PCI. This trial is registered with https://clinicaltrials.gov/ct2/show/ChiCTR-IPR-17012219 (Chinese Clinical Trial Registry, http://www.chictr.org.cn on 02/08/2017).
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Affiliation(s)
- Changqing Sun
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Wuyang Zheng
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Ling Liang
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Zuheng Liu
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Wenchao Sun
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Rong Tang
- Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
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12
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Fras Z, Mikhailidis DP. Have We Learnt all from IMPROVE-IT? Part I. Core Results and Subanalyses on the Effects of Ezetimibe Added to Statin Therapy Related to Age, Gender and Selected Chronic Diseases (Kidney Disease, Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease). Curr Vasc Pharmacol 2021; 19:451-468. [DOI: 10.2174/1570161118999200727224946] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 06/23/2020] [Accepted: 07/03/2020] [Indexed: 11/22/2022]
Abstract
IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) was
a randomized clinical trial (including 18,144 patients) that evaluated the efficacy of the combination of
ezetimibe with simvastatin vs. simvastatin monotherapy in patients with acute coronary syndrome
(ACS) and moderately increased low-density lipoprotein cholesterol (LDL-C) levels (of up to 2.6-3.2
mmol/L; 100-120 mg/dL). After 7 years of follow-up, combination therapy resulted in an additional
LDL-C decrease [to 1.8 mmol/L, or 70 mg/dL, within the simvastatin (40 mg/day) monotherapy arm
and to 1.4 mmol/L, or 53 mg/dL for simvastatin (40 mg/day) + ezetimibe (10 mg/day)] and showed an
incremental clinical benefit [composite of cardiovascular death, nonfatal myocardial infarction, unstable
angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal
stroke; hazard ratio (HR) of 0.936, and 95% CI 0.887-0.996, p=0.016]. Therefore, for very high cardiovascular
risk patients “even lower is even better” regarding LDL-C, independently of the LDL-C
reducing strategy. These findings confirm ezetimibe as an option to treat very-high-risk patients who
cannot achieve LDL-C targets with statin monotherapy. Additional analyses of the IMPROVE-IT (both
prespecified and post-hoc) include specific very-high-risk subgroups of patients (those with previous
acute events and/or coronary revascularization, older than 75 years, as well as patients with diabetes
mellitus, chronic kidney disease or non-alcoholic fatty liver disease). The data from IMPROVE-IT also
provide reassurance regarding longer-term safety and efficacy of the intensification of lipid-lowering
therapy in very-high-risk patients resulting in very low LDL-C levels. We comment on the results of
several (sub) analyses of IMPROVE-IT.
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Affiliation(s)
- Zlatko Fras
- Centre for Preventive Cardiology, Department of Vascular Medicine, Division of Medicine, University Medical Centre, Ljubljana, Slovenia
| | - Dimitri P. Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College Medical School, University College London, London, United Kingdom
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ON THE POSSIBILITY OF USING CARBON ENTEROSORBENTS TO NORMALIZE CHOLESTEROL METABOLISM. BIOTECHNOLOGIA ACTA 2021. [DOI: 10.15407/biotech14.04.064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The creation of effective drugs for the prevention and treatment of atherosclerosis is one of the urgent interdisciplinary tasks for modern chemistry and pharmacology. Given the role of hypercholesterolemia in the development of this disease, it is necessary to remove excess amounts of cholesterol from the body. As an alternative to means of lowering total cholesterol and low-density lipoprotein (LDL) cholesterol, the possibility of using carbon enterosorbents for efferent therapy is considered. Aim. The purpose of the study was to evaluate the sorption capacity of the adsorbents developed by authors in terms of the possibility of cholesterol adsorption. Methods. Using the spectrophotometric method, the sorption of cholesterol on samples of adsorbents obtained by chemical activation of waste from the processing of lignocellulosic raw materials — dogwood and coffee residue has been studied. Results. A comparison of sorption isotherms with the isotherm obtained on the industrial adsorbent SORBEX has been performed. It was shown that the adsorption capacity of carbon adsorbents is primarily determined by their porous structure. The highest sorption values (7,3 mg/g) have been revealed by the sorption material obtained by chemical activation of cornel seed, an intermediate position (6,3 mg/g) is occupied by the adsorbent obtained from the coffee residue. Industrial carbon SORBEX has the lowest sorption values (5,3 mg/g). Conclusions. Calculations by Langmuir’s and Freundlich’s models testify about the accordance of the experimental data to Langmuir’s model. The use of the obtained activated carbons may be one of the effective alternative ways to lower blood cholesterol.
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Boutari C, Karagiannis A, Athyros VG. Rosuvastatin and ezetimibe for the treatment of dyslipidemia and hypercholesterolemia. Expert Rev Cardiovasc Ther 2021; 19:575-580. [PMID: 34102931 DOI: 10.1080/14779072.2021.1940959] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Introduction: Statins are powerful lipid-lowering agents which reduce cardiovascular (CV)-related morbidity and mortality. However, a large proportion of patients cannot attain the target low-density lipoprotein cholesterol (LDL-C) levels, despite receiving maximally tolerated doses of high-intensity statins. Also, adherence to treatment may be reduced due to statin-induced myopathy or other side effects. For these reasons, guidelines recommend adding the cholesterol absorption inhibitor ezetimibe.Areas covered: Authors discuss the main pharmacological characteristics of rosuvastatin and ezetimibe, their lipid-lowering and pleiotropic effects, as well as the clinical effects of the fixed dose combination of these drugs when used to treat dyslipidemia.Expert opinion: The rosuvastatin/ezetimibe combination is safe and effective in patients with hypercholesterolemia or dyslipidemia with or without diabetes and with or without cardiovascular disease. This drug combination enabled higher proportions of patients to achieve recommended LDL-C goals than rosuvastatin monotherapy or the simvastatin/ezetimibe combination, without additional adverse events. Despite the lack of additional CV outcomes data and comparisons with atorvastatin/ezetimibe, rosuvastatin/ezetimibe appears as a potent and generally well-tolerated drug combination eligible for the management of hypercholesterolemia and dyslipidemia in adults. Recently, the 40 mg rosuvastatin/10 mg ezetimibe fixed combination was approved and is also evaluated.
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Affiliation(s)
- Chrysoula Boutari
- Department of Internal Medicine, Aristotle University and School of Medicine, Thessaloniki, Greece
| | - Asterios Karagiannis
- Department of Internal Medicine, Aristotle University and School of Medicine, Thessaloniki, Greece
| | - Vasilios G Athyros
- Department of Internal Medicine, Aristotle University and School of Medicine, Thessaloniki, Greece
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15
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Lee J, Egolum U, Parihar H, Cooley M, Ling H. Effect of Ezetimibe Added to High-Intensity Statin Therapy on Low-Density Lipoprotein Cholesterol Levels: A Meta-Analysis. Cardiol Res 2021; 12:98-108. [PMID: 33738013 PMCID: PMC7935639 DOI: 10.14740/cr1224] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 01/28/2021] [Indexed: 12/11/2022] Open
Abstract
Background Adding ezetimibe to high-intensity statin therapy is used for additional lowering of low-density lipoprotein cholesterol (LDL-C); however, there are little data on the efficacy of ezetimibe when combined with a high-intensity statin. A meta-analysis was performed to evaluate the efficacy of ezetimibe added to high-intensity statin therapy on LDL-C levels. Methods A literature search from database inception to May 2020 was performed using PubMed, EMBASE and Cochrane Central Register of Controlled Trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this meta-analysis, in which the random-effects model was adopted for the calculation of the mean difference (MD). The Cochrane Collaboration's tool for assessing the risk of bias was used to evaluate the quality of the included trials. Results A total of 14 trials with 2,007 patients were included in this study. Compared to the high-intensity statin monotherapy, the MD in LDL-C reduction with high-intensity statin therapy plus ezetimibe was -14.00% (95% confidence interval: -17.78 to -10.22; P < 0.001) with a moderate degree of heterogeneity (P < 0.001, I2 = 66%). No significant publication bias among the included trials was identified. Conclusions Our study found that adding ezetimibe to high-intensity statin therapy provided a significant but attenuated incremental reduction in LDL-C levels. Whether the magnitude of this additional lowering of LDL-C levels would lead to benefits in clinical cardiovascular outcomes needs further investigation.
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Affiliation(s)
- Jayden Lee
- School of Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, GA, USA
| | - Ugochukwu Egolum
- The Heart Center of Northeast Georgia Medical Center, Gainesville, GA, USA
| | - Harish Parihar
- College of Pharmacy, California Health Sciences University, Clovis, CA, USA
| | - Michael Cooley
- School of Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, GA, USA
| | - Hua Ling
- School of Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, GA, USA
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Abstract
The causal relation between elevated levels of LDL-C and cardiovascular disease has been largely established by experimental and clinical studies. Thus, the reduction of LDL-C levels is a major target for the prevention of cardiovascular disease. In the last decades, statins have been used as the main therapeutic approach to lower plasma cholesterol levels; however, the presence of residual lipid-related cardiovascular risk despite maximal statin therapy raised the need to develop additional lipid-lowering drugs to be used in combination with or in alternative to statins in patients intolerant to the treatment. Several new drugs have been approved which have mechanisms of action different from statins or impact on different lipoprotein classes.
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17
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Ma YB, Chan P, Zhang Y, Tomlinson B, Liu Z. Evaluating the efficacy and safety of atorvastatin + ezetimibe in a fixed-dose combination for the treatment of hypercholesterolemia. Expert Opin Pharmacother 2019; 20:917-928. [PMID: 30908086 DOI: 10.1080/14656566.2019.1594776] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Ya-Bin Ma
- The Department of Pharmacy, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Paul Chan
- Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
| | - Yuzhen Zhang
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Brian Tomlinson
- Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Zhongmin Liu
- Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai, China
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18
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Latest Updates on Lipid Management. High Blood Press Cardiovasc Prev 2019; 26:85-100. [PMID: 30877603 DOI: 10.1007/s40292-019-00306-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 02/14/2019] [Indexed: 12/15/2022] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Despite the clinical long-term and near-term benefits of lowering cholesterol in, respectively, primary and secondary prevention of ASCVD, cholesterol levels remain under-treated, with many patients not achieving their recommended targets. The present article will review the latest updates on lipid management with emphases on the different classes of cholesterol-lowering agents and their clinical uses.
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Soran H, Adam S, Durrington PN. Optimising treatment of hyperlipidaemia: Quantitative evaluation of UK, USA and European guidelines taking account of both LDL cholesterol levels and cardiovascular disease risk. Atherosclerosis 2018; 278:135-142. [DOI: 10.1016/j.atherosclerosis.2018.08.040] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 06/26/2018] [Accepted: 08/29/2018] [Indexed: 12/15/2022]
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Ezetimibe in high-risk, previously treated statin patients: a systematic review and network meta-analysis of lipid efficacy. Clin Res Cardiol 2018; 108:487-509. [PMID: 30302558 DOI: 10.1007/s00392-018-1379-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 09/25/2018] [Indexed: 01/01/2023]
Abstract
PURPOSE While statins are used as first-line treatments for high-risk patients with hypercholesterolemia, statin monotherapy is often insufficient to achieve target low-density lipoprotein cholesterol (LDL-C) levels. Second-line treatment options include up-titration of statin dose, switching to a more potent statin, or combination therapy, e.g., with ezetimibe. The aim of this study was to evaluate the efficacy of adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin monotherapy versus doubling the dosage or switching to a higher-potency statin in a population of patients with hypocholesterolemia at high risk of cardiovascular disease (CVD) and who had been previously treated with a statin. METHODS A systematic literature search was performed and evidence bases were established for populations of atorvastatin-, simvastatin-, and rosuvastatin-experienced patients using eligible randomized controlled trials (RCTs). Based on the available data, we constructed networks of evidence and conducted a Bayesian network meta-analysis (NMA) within each statin population. The primary outcome of interest was percent change from baseline in LDL-C. Changes in total cholesterol were explored as a secondary outcome. FINDINGS Across all patient populations, 35 RCTs were identified and included in the evidence base. Among patients on simvastatin therapy, the addition of ezetimibe resulted in a mean difference (MD) in LDL-C of - 13.62% (95% CrI - 19.99, - 6.91; see table below) compared to doubling the starting dose of simvastatin. In the population of patients on atorvastatin therapy, the addition of ezetimibe resulted in an MD in LDL-C of - 14.71% (95% CrI - 16.46, - 12.95) compared to doubling the starting dose of atorvastatin. The addition of ezetimibe to rosuvastatin resulted in an MD in LDL-C of - 14.96% (95% CrI - 17.79, - 12.11), compared to doubling the starting rosuvastatin dose. Similar trends were observed for changes in total cholesterol. IMPLICATIONS Given the available data, the addition of ezetimibe to ongoing simvastatin, atorvastatin, or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CVD compared to doubling the initial statin dose.
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21
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Wong NKP, Nicholls SJ, Tan JTM, Bursill CA. The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications. Int J Mol Sci 2018; 19:E1680. [PMID: 29874886 PMCID: PMC6032203 DOI: 10.3390/ijms19061680] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 05/24/2018] [Accepted: 05/31/2018] [Indexed: 02/06/2023] Open
Abstract
Almost 600 million people are predicted to have diabetes mellitus (DM) by 2035. Diabetic patients suffer from increased rates of microvascular and macrovascular complications, associated with dyslipidaemia, impaired angiogenic responses to ischaemia, accelerated atherosclerosis, and inflammation. Despite recent treatment advances, many diabetic patients remain refractory to current approaches, highlighting the need for alternative agents. There is emerging evidence that high-density lipoproteins (HDL) are able to rescue diabetes-related vascular complications through diverse mechanisms. Such protective functions of HDL, however, can be rendered dysfunctional within the pathological milieu of DM, triggering the development of vascular complications. HDL-modifying therapies remain controversial as many have had limited benefits on cardiovascular risk, although more recent trials are showing promise. This review will discuss the latest data from epidemiological, clinical, and pre-clinical studies demonstrating various roles for HDL in diabetes and its vascular complications that have the potential to facilitate its successful translation.
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Affiliation(s)
- Nathan K P Wong
- Immunobiology Research Group, The Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia.
- Discipline of Medicine, The University of Sydney School of Medicine, Camperdown, NSW 2006, Australia.
- Heart Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
| | - Stephen J Nicholls
- Heart Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
- Adelaide Medical School, Faculty of Health & Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
| | - Joanne T M Tan
- Immunobiology Research Group, The Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia.
- Discipline of Medicine, The University of Sydney School of Medicine, Camperdown, NSW 2006, Australia.
- Heart Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
- Adelaide Medical School, Faculty of Health & Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
| | - Christina A Bursill
- Immunobiology Research Group, The Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia.
- Discipline of Medicine, The University of Sydney School of Medicine, Camperdown, NSW 2006, Australia.
- Heart Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.
- Adelaide Medical School, Faculty of Health & Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
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Sahebkar A, Simental-Mendía LE, Mikhailidis DP, Pirro M, Banach M, Sirtori CR, Ruscica M, Reiner Ž. Effect of statin therapy on plasma apolipoprotein CIII concentrations: A systematic review and meta-analysis of randomized controlled trials. J Clin Lipidol 2018; 12:801-809. [PMID: 29580713 DOI: 10.1016/j.jacl.2018.01.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 01/16/2018] [Accepted: 01/16/2018] [Indexed: 11/24/2022]
Abstract
BACKGROUND Statins are well-established low-density lipoprotein cholesterol-lowering drugs. Elevated apolipoprotein CIII (Apo CIII) levels are associated with elevated triglyceride-rich particles, which are also considered to be a possible risk factor for cardiovascular disease. OBJECTIVE The aim of this meta-analysis of randomized placebo-controlled clinical trials was to assess the effect of statins on Apo CIII concentrations. METHODS Randomized placebo-controlled trials investigating the impact of statin treatment on cholesterol lowering that include lipoprotein measurement were searched in PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar databases (up to July 31, 2017). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on Apo CIII concentrations. RESULTS This meta-analysis of data from 6 randomized placebo-controlled clinical trials (10 statin arms) involving 802 subjects showed that statin therapy significantly decreased circulating Apo CIII concentrations (weighted mean difference [WMD]: -2.71, 95% confidence interval [CI]: -3.74 to -1.68, P < .001; I2: 73.83%). The effect size was robust in the leave-one-out sensitivity analysis and not driven by any single study. Subgroup analysis showed a reduction of Apo CIII concentrations by atorvastatin (WMD: -4.74, 95% CI: -3.74 to -1.68, P = .002; I2: 84.02%), rosuvastatin (WMD: -2.68, 95% CI: -4.52 to -0.84, P = .004; I2: 0%), and lovastatin (WMD: -1.64, 95% CI: -2.22 to -1.07, P < .001; I2: 0%). CONCLUSION This meta-analysis suggests that statin treatment significantly reduces plasma Apo CIII levels.
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Affiliation(s)
- Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, United Kingdom
| | - Matteo Pirro
- Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy
| | - Maciej Banach
- Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Cesare R Sirtori
- Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Željko Reiner
- University Hospital Center Zagreb, Department of Internal medicine, School of Medicine, University of Zagreb, Croatia.
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Bove M, Fogacci F, Cicero AFG. Pharmacokinetic drug evaluation of ezetimibe + simvastatin for the treatment of hypercholesterolemia. Expert Opin Drug Metab Toxicol 2017; 13:1099-1104. [DOI: 10.1080/17425255.2017.1381085] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Marilisa Bove
- Internal and Surgical Medicine Sciences Department, University of Bologna, Bologna, Italy
| | - Federica Fogacci
- Internal and Surgical Medicine Sciences Department, University of Bologna, Bologna, Italy
| | - Arrigo F. G. Cicero
- Internal and Surgical Medicine Sciences Department, University of Bologna, Bologna, Italy
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Davies GM, Vyas A, Baxter CA. Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States. J Med Econ 2017; 20:723-731. [PMID: 28426345 DOI: 10.1080/13696998.2017.1320559] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
AIMS This study assessed the cost-effectiveness of ezetimibe with statin therapy vs statin monotherapy from a US payer perspective, assuming the impending patent expiration of ezetimibe. METHODS A Markov-like economic model consisting of 28 distinct health states was used. Model population data were obtained from US linked claims and electronic medical records, with inclusion criteria based on diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses, and cost-effectiveness analyses. The base-case scenario was used to evaluate the cost-effectiveness of adding ezetimibe 10 mg to statin in patients aged 35-74 years with a history of coronary heart disease (CHD) and/or stroke, and with low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL over a lifetime horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into account the impending patent expiration in the second quarter of 2017. Sub-group analyses included patients with LDL-C levels ≥100 mg/dL and patients with diabetes with LDL-C levels ≥70 mg/dL. RESULTS The lifetime discounted incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was $9,149 per quality-adjusted life year (QALY) for the base-case scenario. For patients with LDL-C levels ≥100 mg/dL, the ICER was $839/QALY; for those with diabetes and LDL-C levels ≥70 mg/dL, it was $560/QALY. One-way sensitivity analyses showed that the model was sensitive to changes in cost of ezetimibe, rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base-case and sub-group analyses. LIMITATIONS Indirect costs or treatment discontinuation estimation were not included. CONCLUSIONS Compared with statin monotherapy, ezetimibe with statin therapy was cost-effective for secondary prevention of CHD and stroke and for primary prevention of these conditions in patients whose LDL-C levels are ≥100 mg/dL and in patients with diabetes, taking into account a 90% cost reduction for ezetimibe.
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Affiliation(s)
| | - Ami Vyas
- b Department of Epidemiology , School of Public Health, Rutgers University , Piscataway , NJ , USA
- c Department of Pharmacy Practice , College of Pharmacy, University of Rhode Island , Kingston , RI , USA
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Ouweneel AB, van der Sluis RJ, Nahon JE, Van Eck M, Hoekstra M. Simvastatin treatment aggravates the glucocorticoid insufficiency associated with hypocholesterolemia in mice. Atherosclerosis 2017; 261:99-104. [DOI: 10.1016/j.atherosclerosis.2017.02.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 01/30/2017] [Accepted: 02/17/2017] [Indexed: 11/26/2022]
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Gomes GB, Zazula AD, Shigueoka LS, Fedato RA, da Costa ABBA, Guarita-Souza LC, Baena CP, Olandoski M, Faria-Neto JR. A Randomized Open-Label Trial to Assess the Effect of Plant Sterols Associated with Ezetimibe in Low-Density Lipoprotein Levels in Patients with Coronary Artery Disease on Statin Therapy. J Med Food 2017; 20:30-36. [PMID: 28098515 DOI: 10.1089/jmf.2016.0042] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Consumption of food products enriched with plant sterols and the use of ezetimibe reduce cholesterol absorption in the intestine and effectively reduce low-density lipoprotein (LDL) plasma levels. We evaluated the therapeutic effect of the ezetimibe+plant sterol association in patients with coronary artery disease still not reaching recommended lipid levels despite the use of statins. We performed a prospective open-label study with 41 patients with stable coronary disease and LDL >70 mg/dL. Patients were randomized into four groups for a 6-week treatment: the control (CT) group remained on the same statin therapy, the ezetimibe (EZ) group received 10 mg/day of ezetimibe, the plant sterol (PS) group received spread enriched with 2 g of plant sterols, and the ezetimibe+PS (EZ+PS) group received 10 mg/day EZ +2 g PS. Initial mean LDL level was 97.4 ± 31.1 mg/dL in control group, 105.1 ± 23.1 mg/dL in EZ group, 95.4 ± 27.7 mg/dL in PS group, and 97.0 ± 8.3 mg/dL in EZ+PS group (P > .05). After 6 weeks of treatment, LDL of patients slightly increased in the control group (+8.9%; P > .05) and dropped in EZ group (-19.1%; P = .06), PS group (-16.6%; P = .01), and EZ+PS group (-27.3%; P < .01). Mean LDL levels after treatment were 70.5 ± 17.9 mg/dL in EZ+PS group, lower than the other groups (control was 106.1 ± 34.9 mg/dL, EZ group was 85.0 ± 35.6 mg/dL, and PS was 79.6 ± 29.7 mg/dL) (P = .05 variance analysis factor [ANOVA]). Body weight, body-mass index, and glucose plasma levels did not change significantly after intervention. The combination of PS+ezetimibe was associated with lower LDL levels and suggests beneficial therapeutic effect against major cardiovascular events.
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Affiliation(s)
- Gisane Biacchi Gomes
- School of Medicine, Pontificia Universidade Catolica do Parana , Curitiba, Brazil
| | - Ana Denise Zazula
- School of Medicine, Pontificia Universidade Catolica do Parana , Curitiba, Brazil
| | | | | | | | | | | | - Marcia Olandoski
- School of Medicine, Pontificia Universidade Catolica do Parana , Curitiba, Brazil
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Abstract
: Since the introduction of HMG-CoA reductase inhibitors, also known as statins, as an adjunct to diet in the treatment of hyperlipidemia and the greater emphasis placed on reducing low-density lipoprotein (LDL) cholesterol levels in the prevention of atherosclerosis and cardiovascular disease (CVD), there has been less focus on the value of lowering serum triglyceride levels. Many patients are aware of their "good" and "bad" cholesterol levels, but they may not be aware of their triglyceride level or of the association between high triglycerides and the development of CVD. In recent years, however, in light of the increasing incidences of obesity, insulin resistance, and type 2 diabetes, lowering triglyceride levels has gained renewed interest. In addition to the focus on lowering LDL cholesterol levels in CVD prevention, clinicians need to be aware of the role of triglycerides-their contribution to CVD, and the causes and treatment of hypertriglyceridemia.
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Filippatos TD, Florentin M, Georgoula M, Elisaf MS. Pharmacological management of diabetic dyslipidemia. Expert Rev Clin Pharmacol 2016; 10:187-200. [DOI: 10.1080/17512433.2017.1263565] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- T. D. Filippatos
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - M. Florentin
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - M. Georgoula
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - M. S. Elisaf
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
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Prevalence of high-risk cardiovascular patients with therapy-resistant hypercholesterolemia. Cardiovasc Endocrinol 2016; 6:81-85. [PMID: 28540139 PMCID: PMC5427976 DOI: 10.1097/xce.0000000000000098] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 09/13/2016] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Hypercholesterolemia is a causal risk factor for cardiovascular diseases, which is recommended to be treated at least in high-risk patients. Yet, currently there is a lack of epidemiological data on the number of high-risk patients in Germany who do not respond adequately to high-dose statin monotherapy or statin therapy in combination with other lipid-lowering agents. METHODS Of a total of over 2.6 million patient records from general practitioners in the IMS Disease Analyzer database, all high-risk cardiovascular patients with hypercholesterolemia who did not reach target low-density lipoprotein-cholesterol (LDL-C) levels despite at least 12 months of maximum lipid-lowering therapy and optimal medication supply (medication possession rate≥80%) were selected over a defined period. RESULTS On the basis of the practice data, a total of 602 133 patients with a high cardiovascular risk who were treated with statin monotherapy or statin combination therapy with optimal medication supply (medication possession rate≥80%) for at least 12 months were identified. Of them, 49 406 patients received high-dose statin therapy, and 51 869 patients received statin therapy in any dose in combination with another lipid-lowering agent. A total of 79 848 high-risk patients did not reach the target LDL-C level of 70 mg/dl or less despite consistent lipid-lowering therapy; of them, 12 808 had a documented LDL-C level of at least 130 mg/dl. CONCLUSION The prevalence of high-risk cardiovascular patients with therapy-resistant hypercholesterolemia is substantial in Germany.
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Nußbaumer B, Glechner A, Kaminski-Hartenthaler A, Mahlknecht P, Gartlehner G. Ezetimibe-Statin Combination Therapy. DEUTSCHES ARZTEBLATT INTERNATIONAL 2016; 113:445-53. [PMID: 27412989 PMCID: PMC4946327 DOI: 10.3238/arztebl.2016.0445] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Revised: 02/24/2016] [Accepted: 02/24/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus. METHODS This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry. RESULTS Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]). CONCLUSION In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.
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Affiliation(s)
- Barbara Nußbaumer
- Danube University Krems, Department for Evidence-based Medicine and Clinical Epidemiology, Krems an der Donau, Austria
| | - Anna Glechner
- Danube University Krems, Department for Evidence-based Medicine and Clinical Epidemiology, Krems an der Donau, Austria
| | - Angela Kaminski-Hartenthaler
- Danube University Krems, Department for Evidence-based Medicine and Clinical Epidemiology, Krems an der Donau, Austria
| | - Peter Mahlknecht
- Danube University Krems, Department for Evidence-based Medicine and Clinical Epidemiology, Krems an der Donau, Austria
| | - Gerald Gartlehner
- Danube University Krems, Department for Evidence-based Medicine and Clinical Epidemiology, Krems an der Donau, Austria
- Research Triangle Institute International, New York, USA
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Abstract
Weight loss, regular exercise, and diet composition modification seem to improve biochemical and histologic abnormalities. Other therapies directed at insulin resistance, oxidative stress, cytoprotection, and fibrosis may also offer benefits. Insulin sensitizers and vitamin E seem to be the most promising; however, they cause side effects. A multifaceted approach of lifestyle modifications, weight loss, and pharmacotherapy can be used in combination, but no single treatment approach has proved universally applicable to the general population with nonalcoholic steatohepatitis (NASH). Continuous clinical and preclinical studies on existing and potential drugs are needed to improve treatment of nonalcoholic fatty liver disease/NASH.
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Affiliation(s)
- Swaytha Ganesh
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Presbyterian, M2, C-Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
| | - Vinod K Rustgi
- Liver Transplantation, The Thomas Starzl Transplant Institute, UPMC Montefiore, Room N758.1, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA
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Kei AA, Filippatos TD, Elisaf MS. The safety of ezetimibe and simvastatin combination for the treatment of hypercholesterolemia. Expert Opin Drug Saf 2016; 15:559-69. [PMID: 26898906 DOI: 10.1517/14740338.2016.1157164] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
INTRODUCTION In the light of the most recent and stricter dyslipidemia treatment guidelines, the need for combination hypolipidemic therapy is increasing. Ezetimibe plus simvastatin is available as a fixed dose therapy offering an efficient hypolipidemic treatment choice. Based on the positive results of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial, the use of this drug combination is expected to increase in the next years. AREAS COVERED This review discusses the current evidence regarding the safety of ezetimibe/simvastatin combination. Current evidence regarding possible associated side effects (musculoskeletal, gastrointestinal, endocrine, hematological, renal, ophthalmologic, allergic, malignancy) and drug interactions of this combination is thoroughly discussed. EXPERT OPINION Ezetimibe and simvastatin treatment, either as a single pill or the combined use of the individual compounds, offers limited additional risk compared with simvastatin monotherapy and comprises a safe and efficient choice for dyslipidemia treatment in high-risk and diabetic patients.
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Affiliation(s)
- Anastazia A Kei
- a Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece
| | - Theodosios D Filippatos
- a Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece
| | - Moses S Elisaf
- a Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece
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Abstract
INTRODUCTION Statins are evidence-based drugs to prevent cardiovascular (CV) disease. However, their benefits have been disputed by a statin-related increased risk of new onset diabetes (NOD) in randomized controlled trials and meta-analyses. AREAS COVERED This review provides an update based on recent outstanding evidence on the statin effect on the risk of diabetes. It also describes mechanisms potentially explaining adverse effects of statins on glucose homeostasis. PubMed was searched for original articles and reviews published from January 2010 (inclusive) to May 2015 (inclusive), which include the Search terms statins, diabetes, glucose, and insulin. NOD risk seems to be more relevant with high-intensity rather than with low-intensity statin treatment. Also, this risk is particularly increased in patients at risk for the development of diabetes. It appears that statins adversely affect glucose homeostasis in parallel with their 3-hydroxy-3-methylglutaryl-coenzyme A inhibition capacity. It was suggested that lipophilic statins are more diabetogenic than the hydrophilic ones. Mechanisms explaining statin diabetogeneicity include impaired insulin secretion by pancreatic β cells together with increased insulin resistance of various tissues. EXPERT OPINION The CV outcome benefits from statin use outweigh the diabetes menace. However, patients at risk for the development of diabetes should be prescribed statins with caution.
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Affiliation(s)
- Aris P Agouridis
- a 1 Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free London Foundation Trust , Pond Street, London, UK
- b 2 University of Ioannina, Department of Internal Medicine, Medical School , GR 45110 Ioannina, Greece +30 26 51 00 75 09 ; +30 26 51 00 70 16 ;
| | - Michael S Kostapanos
- c 3 Cambridge University Hospitals NHS Foundation Trust, Clinical Pharmacology Unit, Addenbrooke's Hospital , Cambridge, UK
| | - Moses S Elisaf
- b 2 University of Ioannina, Department of Internal Medicine, Medical School , GR 45110 Ioannina, Greece +30 26 51 00 75 09 ; +30 26 51 00 70 16 ;
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Filippatos TD, Elisaf MS. Statin–Ezetimibe Combination Therapy In Diabetic Individuals. Angiology 2015; 67:507-9. [DOI: 10.1177/0003319715598887] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
| | - Moses S. Elisaf
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
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Athyros VG, Tziomalos K, Katsiki N, Doumas M, Karagiannis A, Mikhailidis DP. Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update. World J Gastroenterol 2015; 21:6820-6834. [PMID: 26078558 PMCID: PMC4462722 DOI: 10.3748/wjg.v21.i22.6820] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 03/31/2015] [Accepted: 05/07/2015] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.
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Abstract
General thinking has previously centered on managing carotid artery stenosis (CAS) by carotid endarterectomy and subsequently, stenting for higher risk patients. However for CAS and other forms of vascular disease, especially when asymptomatic, there is new emphasis on defining underlying mechanisms. Knowledge of these mechanisms can lead to medical treatments that result in possible atherosclerotic plaque stabilization, and even plaque regression, including in the patient with CAS. For now, the key medication class for a medical approach are the statins. Their use is supported by good cardiovascular clinical trial evidence including some directed carotid artery studies, especially with a demonstrated decrease in carotid intima-media thickness. Procedural controversy still exists but the current era in medicine offers significant support for medical management of asymptomatic CAS while techniques to recognize the vulnerable plaque evolve. If CAS converts to a symptomatic status, early referral for endarterectomy or stenting is indicated.
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Affiliation(s)
- Thomas F Whayne
- Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, Kentucky
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Agouridis AP, Nair DR, Mikhailidis DP. Strategies to overcome statin intolerance. Expert Opin Drug Metab Toxicol 2015; 11:851-5. [DOI: 10.1517/17425255.2015.1027685] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Affiliation(s)
- Aris P Agouridis
- Department of Internal Medicine Medical School, University of Ioannina Ioannina , Greece
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40
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Li L, Zhang M, Su F, Li Y, Shen Y, Shen J, Zhang D. Combination therapy analysis of ezetimibe and statins in Chinese patients with acute coronary syndrome and type 2 diabetes. Lipids Health Dis 2015; 14:10. [PMID: 25879728 PMCID: PMC4342190 DOI: 10.1186/s12944-015-0004-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 01/27/2015] [Indexed: 02/02/2023] Open
Abstract
Background Dyslipidemia management situation in Chinese patients with high risk and very high risk has been demonstrated very low, despite the wide use of statins. The effects and safety of the combined treatment of ezetimibe (EZ) and statins in Chinese patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM) remain unknown. Methods Chinese Patients with ACS and T2DM were divided into the statins group (n = 40) and the combination group of EZ and statins (n = 44). In order to evaluate the clinical effects on lipids-lowering, systemic inflammation response and clinical safety, the follow-up of all patients was carried out at day 7th and 30th after treatment. Results The level of low-density lipoprotein cholesterol (LDL-C) in combination group and statins group was 1.87 ± 0.42 and 2.18 ± 0.58 mmol/L at day 7th, 1.51 ± 0.29 and 1.94 ± 0.49 mmol/L at day 30th, respectively. The control rates of LDL-C level in the combination group and the statins group were 77% and 45% at day 30th, respectively. There was no significant improvement on high-density lipoprotein cholesterol (HDL-C) level during follow-up. The triglyceride (TG) levels were significantly reduced in both groups, while no obvious difference was observed between two groups. No significant difference on serum high-sensitivity C-reactive protein (hs-CRP) level between two groups was observed. Moreover, we did not observe any significant correlation between serum lipids levels and serum hs-CRP level during follow-up. The liver dysfunction and muscle related side effects (MRSE), creatine kinase (CK) and myopathy were not observed in both groups. Conclusion Our study demonstrated that it is feasible to initiate combination therapy during acute phase for Chinese patients with ACS and T2DM, which can bring more significant effect on LDL-C-lowering and improve the control rate of LDL-C level with good safety.
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Affiliation(s)
- Lulu Li
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China. .,Charite University of Berlin, Berlin, Germany.
| | - Minli Zhang
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Fuxiang Su
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Yang Li
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Yali Shen
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Jie Shen
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Daqing Zhang
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
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Barkas F, Milionis H, Kostapanos MS, Mikhailidis DP, Elisaf M, Liberopoulos E. How effective are the ESC/EAS and 2013 ACC/AHA guidelines in treating dyslipidemia? Lessons from a lipid clinic. Curr Med Res Opin 2015; 31:221-228. [PMID: 25418708 DOI: 10.1185/03007995.2014.982751] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/27/2014] [Indexed: 12/15/2022]
Abstract
OBJECTIVE There is a paucity of data regarding the attainment of lipid-lowering treatment goals according to the recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The aim of the present study was to assess how applicable these 2013 recommendations are in the setting of an Outpatient University Hospital Lipid Clinic. METHODS This was a retrospective (from 1999 to 2013) observational study including 1000 consecutive adults treated for hyperlipidemia and followed up for ≥3 years. Comparisons for the applicability of current European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) and recent ACC/AHA guidelines were performed. RESULTS Achievement rates of low density lipoprotein cholesterol (LDL-C) targets set by ESC/EAS were 21%, 44% and 62% among patients at very high, high and moderate cardiovascular risk, respectively, receiving statin monotherapy. Among individuals on high-intensity statins only 47% achieved the anticipated ≥50% LDL-C reduction, i.e. the ACC/AHA target. The corresponding rate was significantly greater among those on statin + ezetimibe (76%, p < 0.05). Likewise, higher rates of LDL-C target attainment according to ESC/EAS guidelines were observed in patients on statin + ezetimibe compared with statin monotherapy (37, 50 and 71% for the three risk groups, p < 0.05 for the very high risk group). CONCLUSION The application of the ACC/AHA guidelines may be associated with undertreatment of high risk patients due to suboptimal LDL-C response to high-intensity statins in clinical practice. Adding ezetimibe substantially increases the rate of the ESC/EAS LDL-C target achievement together with the rate of LDL-C lowering response suggested by the ACC/AHA.
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Affiliation(s)
- Fotios Barkas
- Department of Internal Medicine, School of Medicine, University of Ioannina , Ioannina , Greece
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Kouvelos GN, Arnaoutoglou EM, Milionis HJ, Raikou VD, Papa N, Matsagkas MI. The effect of adding ezetimibe to rosuvastatin on renal function in patients undergoing elective vascular surgery. Angiology 2015; 66:128-135. [PMID: 24458801 DOI: 10.1177/0003319713519492] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
We compared the effects of lipid lowering with rosuvastatin (RSV) monotherapy versus intensified treatment by combining RSV with ezetimibe (EZT) on kidney function in patients undergoing vascular surgery. Patients were randomly assigned to either 10 mg/d RSV (n = 136) or RSV 10 mg/d plus EZT 10 mg/d (RSV/EZT, n = 126). At 12 months, a similar decrease in estimated glomerular filtration rate (eGFR) was noted. Patients who achieved a low-density lipoprotein cholesterol (LDL-C) of <100 mg/dL had less eGFR decrease than those patients having an LDL-C limit of more than 100 mg/dL. There were no significant changes in the urinary total protein to creatinine ratio in either group. Significant microalbuminuria was evident in both the groups. Patients undergoing vascular surgery show deterioration in their renal function during the first year, despite statin therapy. Intensified lipid-lowering therapy by adding EZT does not appear to have any renoprotective effect.
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Affiliation(s)
- George N Kouvelos
- Department of Surgery-Vascular Surgery Unit, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Eleni M Arnaoutoglou
- Department of Anesthesiology, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Haralampos J Milionis
- Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Vaia D Raikou
- First Department of Internal Medicine, School of Medicine, University of Athens, Athens, Greece
| | - Nektario Papa
- Department of Surgery-Vascular Surgery Unit, School of Medicine, University of Ioannina, Ioannina, Greece
| | - Miltiadis I Matsagkas
- Department of Surgery-Vascular Surgery Unit, School of Medicine, University of Ioannina, Ioannina, Greece
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Athyros VG, Katsiki N, Karagiannis A, Mikhailidis DP. High-intensity statin therapy and regression of coronary atherosclerosis in patients with diabetes mellitus. J Diabetes Complications 2015; 29:142-5. [PMID: 25456820 DOI: 10.1016/j.jdiacomp.2014.10.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Revised: 10/01/2014] [Accepted: 10/04/2014] [Indexed: 11/25/2022]
Abstract
Recommended low-density lipoprotein cholesterol (LDL-C) levels for patients with documented cardiovascular disease (CVD) are <100mg/dL (2.6mmol/l) with further reduction to <70mg/dL (1.8mmol/l) for higher-risk patients. High-intensity statin treatment may halt the progression as well as stabilize and induce regression of coronary atheromatous plaques while lowering CVD event rates. Diabetes mellitus (DM) is a major negative determinant of coronary artery plaque regression during statin therapy. However, regression of coronary atherosclerosis in DM patients is feasible to the same degree as in those without DM when very low LDL-C values (<70mg/dL; 1.8mmol/l) are achieved with high intensity statin treatment. The recent 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults suggest to abandon specific LDL-C treatment targets. This strategy may deprive high risk patients, such as those with DM, from very high intensity statin treatment or drug combinations aiming to achieve very low LDL-C levels in order to reduce clinical events.
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Affiliation(s)
- Vasilios G Athyros
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Asterios Karagiannis
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry (Vascular Prevention Clinic), Royal Free Hospital Campus, University College Medical School, University College London, London, UK.
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Athyros VG, Katsiki N, Rizzo M. Undertreatment of dyslipidemia: from the Arabian Gulf to the USA. Time to solve this problem! Curr Med Res Opin 2014; 30:2425-8. [PMID: 25233064 DOI: 10.1185/03007995.2014.966189] [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] [Indexed: 11/23/2022]
Abstract
Undertreatment of dyslipideamia is a universal problem and reduces the efficasy of hypolipidaemic drugs to reduce cardiovascular event rates. The means to face this problem are available and should be utilized to optimize dyslipidaemia control and clinical outcomes.
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Affiliation(s)
- Vasilios G Athyros
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital , Thessaloniki , Greece
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Tziomalos K. Lipid-lowering agents in the management of nonalcoholic fatty liver disease. World J Hepatol 2014; 6:738-744. [PMID: 25349644 PMCID: PMC4209418 DOI: 10.4254/wjh.v6.i10.738] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2014] [Revised: 08/22/2014] [Accepted: 09/06/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.
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Affiliation(s)
- Konstantinos Tziomalos
- Konstantinos Tziomalos, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece
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Katsiki N, Mikhailidis DP, Nair DR. The effects of antiepileptic drugs on vascular risk factors: A narrative review. Seizure 2014; 23:677-84. [DOI: 10.1016/j.seizure.2014.05.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 05/21/2014] [Accepted: 05/24/2014] [Indexed: 12/13/2022] Open
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Bertolami A, Botelho PB, Macedo LF, Abdalla DS, Faludi AA, Galasso M, Castro IA. Effect of plant sterols compared with ezetimibe on oxidative stress in patients treated with statins. J Funct Foods 2014. [DOI: 10.1016/j.jff.2014.05.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Deharo P, Pankert M, Quilici J, Grosdidier C, Verdier V, Bonnet G, Morange P, Alessi MC, Bonnet JL, Cuisset T. Safety and effectiveness of the association ezetimibe-statin (E-S) versus high dose rosuvastatin after acute coronary syndrome: the SAFE-ES study. Ann Cardiol Angeiol (Paris) 2014; 63:222-7. [PMID: 24861503 DOI: 10.1016/j.ancard.2014.04.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Accepted: 04/15/2014] [Indexed: 11/16/2022]
Abstract
BACKGROUND Statin therapy is a cornerstone therapy for secondary prevention after acute coronary syndrome (ACS). However, the use of these drugs can be limited by side effects, mainly muscular pain. Ezetimibe is a newer lipid-lowering agent, with fewer side effects. AIMS The present study was designed to compare a commercially available association of ezetimibe and simvastatin (E-S) to high dose Rosuvastatin on cholesterol and muscular enzyme levels and occurrence of muscular pain. METHODS All consecutive ACS statin-naïve patients with LDL cholesterol (LDL-C)>100mg/dL randomly received either high dose statin (Rosuvastatin 20mg) or E-S 10/40-mg. All patients had one-month follow-up with biological testing and clinical examination. We compared the two groups on the biological efficiency and incidence of muscular pain. RESULTS One hundred and twenty-eight patients were randomized; 64 received E-S and 64 Rosuvastatin. In the two groups, the lowering of LDL-C level (Δ=51%) at one month was significant (P<0.01) without any difference in the rate of lowering on LDL-C or HDL-C suggesting that E-S is as effective as high dose Rosuvastatin (P=0.77 and P=0.99). The rate of patients reaching the objective of LDL-C<100mg/dL (45%) and LDL-C<70mg/dL (51%) was not different in the two clusters (P=0.65). Incidence of muscular pain was 15% higher in patients treated with Rosuvastatin (P=0.01) without any difference on CPK level (P=0.6). CONCLUSION Using an association of E-S in an effective alternative strategy to high dose Rosuvastatin with a lower incidence of muscular pain, which might impact adherence to medication after ACS.
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Affiliation(s)
- P Deharo
- Département de cardiologie, CHU Timone, 13385 Marseille, France; Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France.
| | - M Pankert
- Département de cardiologie, CHU Timone, 13385 Marseille, France; Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France
| | - J Quilici
- Département de cardiologie, CHU Timone, 13385 Marseille, France; Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France
| | - C Grosdidier
- Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France; Laboratoire d'hématologie, CHU Timone, 13385 Marseille, France
| | - V Verdier
- Équipe mobile d'aide à l'investigation (EMAI), Assistance publique-Hôpitaux de Marseille, 13385 Marseille, France
| | - G Bonnet
- Département de cardiologie, CHU Timone, 13385 Marseille, France; Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France
| | - P Morange
- Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France; Laboratoire d'hématologie, CHU Timone, 13385 Marseille, France
| | - M-C Alessi
- Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France; Laboratoire d'hématologie, CHU Timone, 13385 Marseille, France
| | - J-L Bonnet
- Département de cardiologie, CHU Timone, 13385 Marseille, France; Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France
| | - T Cuisset
- Département de cardiologie, CHU Timone, 13385 Marseille, France; Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », 13385 Marseille, France; Faculté de médecine, Aix-Marseille université, 13385 Marseille, France
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Marrett E, Zhao C, Zhang NJ, Zhang Q, Ramey DR, Tomassini JE, Tershakovec AM, Neff DR. Limitations of real-world treatment with atorvastatin monotherapy for lowering LDL-C in high-risk cardiovascular patients in the US. Vasc Health Risk Manag 2014; 10:237-46. [PMID: 24851051 PMCID: PMC4008284 DOI: 10.2147/vhrm.s54886] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Guidelines endorse statin therapy for lowering low-density lipoprotein cholesterol (LDL-C) to recommended levels, in patients with cardiovascular disease (CVD) risk, if needed, after lifestyle changes. Atorvastatin is a common statin with greater LDL-C lowering efficacy than most other statins; its availability in generic form will likely increase its use. This study assessed attainment of guideline-recommended LDL-C levels in high-risk CVD patients treated with atorvastatin monotherapy. METHODS Analyses of two retrospective US cohorts of patients who received a prescription for atorvastatin monotherapy between January 1, 2008 and December 31, 2010 (index date defined as first prescription date) in the GE Centricity Electronic Medical Record (EMR) (N=10,693) and Humana Medicare (N=16,798) databases. Eligible patients were ≥18 years, diagnosed with coronary heart disease or atherosclerotic vascular disease, with ≥1 LDL-C measurement between 3 months and 1 year postindex date, and continuously enrolled for 1 year prior to and following the index date. RESULTS Of the eligible patients, 21.8%, 29.6%, 29.9%, and 18.7% (GE Centricity EMR) and 25.4%, 32.9%, 27.8%, and 14.0% (Humana Medicare) received 10, 20, 40, and 80 mg doses of atorvastatin, respectively. The mean ± standard deviation (SD) follow-up LDL-C levels were 2.1±0.8 mmol/L (83±30 mg/dL) and 2.3±0.8 mmol/L (88±31 mg/dL) for the GE Centricity EMR and Humana Medicare cohorts, respectively. Regardless of dose, only 28.3%-34.8% of patients had LDL-C levels <1.8 mmol/L (<70 mg/dL), and 72.0%-78.0% achieved LDL-C <2.6 mmol/L (<100 mg/dL) in both cohorts. As many as 41% and 13% of patients had LDL-C levels ≥0.5 mmol/L (≥20 mg/dL) above LDL-C 1.8 mmol/L (70 mg/dL) and 2.6 mmol/L (100 mg/dL), respectively, in both cohorts; these percentages were generally similar across atorvastatin doses. CONCLUSION In this real-world US setting, a large number of high-risk CVD patients did not attain guideline-recommended LDL-C levels with atorvastatin monotherapy. More than 65% of the patients had LDL-C levels >1.8 mmol/L (>70 mg/dL), and of these, 30%-40% had LDL-C levels ≥0.5 mmol/L (≥20 mg/dL) above this, regardless of dose. This suggests that more effective lipid-lowering strategies, such as statin uptitration, switching to a higher efficacy statin, and/or combination therapy, may be required to achieve optimal LDL-C lowering in high-risk patients.
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Affiliation(s)
| | | | - Ning Jackie Zhang
- College of Health and Public Affairs, University of Central Florida, Orlando, FL, USA
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Abstract
Metabolic syndrome is defined by a constellation of interconnected physiological, biochemical, clinical, and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus, and all cause mortality. Insulin resistance, visceral adiposity, atherogenic dyslipidemia, endothelial dysfunction, genetic susceptibility, elevated blood pressure, hypercoagulable state, and chronic stress are the several factors which constitute the syndrome. Chronic inflammation is known to be associated with visceral obesity and insulin resistance which is characterized by production of abnormal adipocytokines such as tumor necrosis factor α , interleukin-1 (IL-1), IL-6, leptin, and adiponectin. The interaction between components of the clinical phenotype of the syndrome with its biological phenotype (insulin resistance, dyslipidemia, etc.) contributes to the development of a proinflammatory state and further a chronic, subclinical vascular inflammation which modulates and results in atherosclerotic processes. Lifestyle modification remains the initial intervention of choice for such population. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioural strategies. Pharmacological treatment should be considered for those whose risk factors are not adequately reduced with lifestyle changes. This review provides summary of literature related to the syndrome's definition, epidemiology, underlying pathogenesis, and treatment approaches of each of the risk factors comprising metabolic syndrome.
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Affiliation(s)
- Jaspinder Kaur
- Ex-Servicemen Contributory Health Scheme (ECHS) Polyclinic, Sultanpur Lodhi, Kapurthala District 144626, India
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