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Wang W, Wang X, Zhang L, Zhang J, Man F, Pan Q, Guo L. Treatment Outcomes of Clopidogrel in Patients With ACS and Diabetes Undergoing PCI-Analysis of Beijing Municipal Medical Insurance Database. Front Endocrinol (Lausanne) 2021; 12:713849. [PMID: 34394007 PMCID: PMC8362599 DOI: 10.3389/fendo.2021.713849] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/05/2021] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND AND AIMS Several clinical trials have proved the efficacy of clopidogrel treatment for patients with percutaneous coronary intervention. There are few large-scale studies to identify the mortality associated with different durations of treatment of clopidogrel in patients with diabetes and ACS undergoing PCI in the Chinese population. The objective of this analysis was to determine the efficacy of long-term clopidogrel therapy (≥12 months) versus short-term use (<12 months) in Chinese patients with diabetes after PCI. METHODS AND RESULTS We used the Beijing Municipal Medical Insurance Database provided by the Beijing Municipal Medical Insurance Bureau. The Beijing Municipal Medical Insurance Database contained medical data of about 16 million people, including about 990,000 patients with diabetes and a history of taking antidiabetic medicines. Patients were divided into two groups, one group of 9,116 patients receiving consecutive clopidogrel for one year or more, and another group of 3290 patients receiving consecutive clopidogrel for less than one year. The primary outcomes of this analysis were the risk of all-cause death, myocardial infarction, and revascularization. In patients with diabetes after PCI, long-term clopidogrel treatment was associated with a reduced risk of all-cause death (HR, 0.57[95%CI, 0.49-0.67], P<0.0001), myocardial infarction (HR, 0.79[95%CI, 0.68-0.93], P=0.0035) and an increased risk of angina (HR, 1.18[95%CI, 1.10-1.27], P<0.0001]) and revascularization (HR, 1.07[95%CI, 1.01-1.13], P=0.02]). There was no significant difference in the prevalence of all-cause re-hospitalization, diabetes-related re-hospitalization, and cerebrovascular re-hospitalization. CONCLUSION The present study concluded that long-term dual antiplatelet therapy including clopidogrel and aspirin could decrease the risks of all-cause death, myocardial infarction. But it could increase the risks of angina and revascularization. Further studies should interpret the cause of this question.
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Affiliation(s)
| | | | | | | | | | - Qi Pan
- *Correspondence: Lixin Guo, ; Qi Pan,
| | - Lixin Guo
- *Correspondence: Lixin Guo, ; Qi Pan,
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Leonov KA, Vishenkova DA, Bykov VV, Bakibaev AA. Determination of a New Antiulcer Drug in Rat Blood Plasma by Liquid Chromatography–Mass Spectrometry. JOURNAL OF ANALYTICAL CHEMISTRY 2019. [DOI: 10.1134/s1061934819140089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Bundhun PK, Teeluck AR, Bhurtu A, Huang WQ. Is the concomitant use of clopidogrel and Proton Pump Inhibitors still associated with increased adverse cardiovascular outcomes following coronary angioplasty?: a systematic review and meta-analysis of recently published studies (2012 - 2016). BMC Cardiovasc Disord 2017; 17:3. [PMID: 28056809 PMCID: PMC5221663 DOI: 10.1186/s12872-016-0453-6] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 12/22/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Controversies were previously observed with the concomitant use of clopidogrel and Proton Pump Inhibitors (PPIs), especially omeprazole, following coronary angioplasty. Even though several studies showed no interaction between clopidogrel and PPIs, questions have been raised about the decrease in antiplatelet effects of clopidogrel with PPIs. A previously published meta-analysis showed concomitant use of clopidogrel and PPIs to be associated with higher adverse cardiovascular outcomes. However, data which were used were extracted from studies published before the year 2012. Whether these controversies still exist in this new era is not clear. Therefore, we aim to show if the concomitant use of clopidogrel and PPIs is still associated with higher adverse outcomes following Percutaneous Coronary Intervention (PCI) using data obtained from recently published studies (2012 to 2016). METHODS Electronic databases were searched for recent publications (2012-2016) comparing (clopidogrel plus PPIs) versus clopidogrel alone following PCI. Adverse cardiovascular outcomes were considered as the clinical endpoints. Odds Ratios (OR) with 95% Confidence Intervals (CI) were used as the statistical parameters and the pooled analyses were performed with RevMan 5.3 software. RESULTS Eleven studies with a total number of 84,729 patients (29,235 patients from the PPIs group versus 55,494 patients from the non-PPIs group) were included. Results of this analysis showed that short term mortality and Target Vessel Revascularization (TVR) significantly favored the non-PPIs group with OR: 1.55; 95% CI: 1.43-1.68, P < 0.00001 and OR: 1.26; 95% CI: 1.06-1.49, P = 0.009 respectively. Long-term Major Adverse Cardiac Events (MACEs), Myocardial Infarction (MI), Stent Thrombosis (ST) and TVR significantly favored patients who did not use PPIs with OR: 1.37; 95% CI: 1.23-1.53, P < 0.00001, OR: 1.41; 95% CI: 1.26-1.57, P < 0.00001 and OR: 1.38; 95% CI: 1.13-1.70, P = 0.002 and OR: 1.28; 95% CI: 1.01-1.61, P = 0.04 respectively. However, the result for long term mortality was not statistically significant. CONCLUSION The combined use of clopidogrel with PPIs is still associated with significantly higher adverse cardiovascular events such as MACEs, ST and MI following PCI supporting results of the previously published meta-analysis. However, long-term mortality is not statistically significant warranting further analysis with randomized patients.
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Affiliation(s)
- Pravesh Kumar Bundhun
- Institute of Cardiovascular Diseases, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China
| | | | - Akash Bhurtu
- Guangxi Medical University, Nanning, Guangxi, 530027, People's Republic of China
| | - Wei-Qiang Huang
- Institute of Cardiovascular Diseases, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
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Vernaz N, Rollason V, Adlere L, Combescure C, Poncet A, Bonnabry P, Desmeules J. Snapshot of the prescribing practice for the clopidogrel and esomeprazole coprescription and cost evaluation of the application guidelines. Pharmacol Res Perspect 2016; 4:e00234. [PMID: 27433344 PMCID: PMC4876144 DOI: 10.1002/prp2.234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 02/29/2016] [Indexed: 11/20/2022] Open
Abstract
The antiplatelet clopidogrel and the proton pump inhibitor esomeprazole demonstrate a pharmacokinetic interaction through CYP2C19 that could translate into clinical inefficacy of clopidogrel. No medical consensus as to their coprescription has been reached, and different guidelines are available. We evaluated the prescribing practices at the Geneva University Hospitals (HUG) by measuring whether the coprescription was staggered as suggested by experts. We estimated the financial impact of different implementation guidelines. We used the HUG electronic patient records to follow the physicians' prescriptions and the administration by nurses from January 2013 to April 2014. We performed a time series analysis to assess 15 years of proton pump inhibitors (PPIs) and antiplatelet drug use. “Extra costs” were calculated assuming that clopidogrel or esomeprazole would replace prasugrel or ticagrelor and pantoprazole or ranitidine, respectively. Only 10.8% of the patient medical orders for the clopidogrel and esomeprazole coprescription specified to stagger the administration, 12.6% specified a concomitant coprescription, and 76.6% had no clear information. A high rate of 49.6% of the nurses staggered the clopidogrel and esomeprazole coprescription when no clear information was given. We found a statistically significant decrease in clopidogrel use after the publication of the OCLA (Omeprazole–CLopidogrel–Aspirin) study and a significant increase in the trend of esomeprazole. Alternative treatments to avoid this interaction are cost ineffective or offer therapeutic options of lesser quality. We observed a high rate of 56.2% of the clopidogrel and esomeprazole coprescription in our hospital and can therefore not ignore the PK/PD interaction. The most common prescription practice was to not specify the time frame of administration, which was translated by nurses in 49.6% of the cases to a scheduled staggered coprescription of clopidogrel and esomeprazole. As long as no consensus has been reached, the medical orders time frame information should be mandatory to allow a clear and harmonious staggering strategy.
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Affiliation(s)
| | - Victoria Rollason
- Division of Clinical Pharmacology and Toxicology; Geneva University Hospitals; Geneva Switzerland
| | - Liene Adlere
- School of Pharmaceutical Sciences; University of Geneva; University of Lausanne; Geneva University Hospitals; Geneva Switzerland
| | - Christophe Combescure
- Division of Clinical Epidemiology; University of Geneva; Geneva University Hospitals; Geneva Switzerland
| | - Antoine Poncet
- Division of Clinical Epidemiology; University of Geneva; Geneva University Hospitals; Geneva Switzerland
| | - Pascal Bonnabry
- Pharmacy; Geneva University Hospitals; Geneva Switzerland
- School of Pharmaceutical Sciences; University of Geneva; University of Lausanne; Geneva University Hospitals; Geneva Switzerland
| | - Jules Desmeules
- Division of Clinical Pharmacology and Toxicology; Geneva University Hospitals; Geneva Switzerland
- School of Pharmaceutical Sciences; University of Geneva; University of Lausanne; Geneva University Hospitals; Geneva Switzerland
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5
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Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy. Mol Biol Rep 2016; 43:473-84. [DOI: 10.1007/s11033-016-3983-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 04/04/2016] [Indexed: 01/18/2023]
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Guérin A, Mody R, Carter V, Ayas C, Patel H, Lasch K, Wu E. Changes in Practice Patterns of Clopidogrel in Combination with Proton Pump Inhibitors after an FDA Safety Communication. PLoS One 2016; 11:e0145504. [PMID: 26727382 PMCID: PMC4699636 DOI: 10.1371/journal.pone.0145504] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 12/05/2015] [Indexed: 01/01/2023] Open
Abstract
Objectives In 2009, the FDA issued a warning that omeprazole–a proton pump inhibitor (PPI)–reduces the antithrombotic effect of clopidogrel by almost half when taken concomitantly. This study aims to analyze the impact of the FDA Safety Communications on prescribing clopidogrel together with PPIs. Methods This retrospective study identified clopidogrel users from the Truven Health Analytics MarketScan Databases (01/2006–12/2012). Rates of clopidogrel-PPI combination therapy were estimated in 6-month intervals for patients with ≥1 clopidogrel prescription fill, then were analyzed pre- and post-safety communication (11/17/2009). Analyses were also conducted by grouping PPIs into CYP2C19 inhibitors (omeprazole and esomeprazole) and CYP2C19 non-inhibitors (pantoprazole, lansoprazole, dexlansoprazole, and rabeprazole). Results Overall, 483,074 patients met the selection criteria; of these, 157,248 used a clopidogrel-PPI combination. On average, 30.5% of patients in the pre- and 19.9% in the post-communication period used a clopidogrel-PPI combination therapy. Among clopidogrel users, the probability of using clopidogrel-PPI combinations fell by over 40% in the post-communication period (OR = 0.57; p<0.001); the proportion of patients using esomeprazole fell from 12.9% to 5.3%, and the proportion using omeprazole fell from 10.1% to 6.3%. Among combination therapy users, the probability of patients using a combination with a CYP2C19 inhibitor decreased by 53% (OR = 0.47; p<0.001); however, 31.5% of patients were still prescribed a clopidogrel-PPI combination therapy. Trends were similar for all and newly treated patients, regardless of clopidogrel indication and physician specialty. Conclusions The FDA Safety Communication resulted in a reduction in the number of patients undergoing combination therapy; however approximately one-third of patients still used combination therapy post-communication.
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Affiliation(s)
| | - Reema Mody
- Takeda Pharmaceuticals International, Inc., Health Economics and Outcomes Research, Deerfield, Illinois, United States of America
| | | | | | - Haridarshan Patel
- Immensity Consulting, Inc., Chicago, Illinois, United States of America
| | - Karen Lasch
- Takeda Pharmaceuticals International, Inc., Health Economics and Outcomes Research, Deerfield, Illinois, United States of America
| | - Eric Wu
- Analysis Group, Inc., Boston, Massachusetts, United States of America
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Duffy D, Rooney B, Adams S, Whellan DJ. PA32540 for the secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers. Expert Rev Cardiovasc Ther 2014; 12:1251-60. [PMID: 25300316 PMCID: PMC4743601 DOI: 10.1586/14779072.2014.967214] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Prescribed in patients with a history of myocardial infarction, stroke, transient ischemic attack, coronary intervention or bypass surgery, aspirin is one of the medications most commonly used in the secondary prevention of cardiovascular diseases. It has become a mainstay of therapy after years of solid evidence supporting its efficacy in clinical trials. However, a number of risks and side effects accompany its benefits, including the notable risk of bleeding and gastrointestinal side effects. Numerous mechanisms have been proposed to attenuate these effects to promote adherence and to expand the population for which aspirin is a reasonable treatment option. A polypill or combination formulation that includes a proton pump inhibitor, a drug commonly prescribed alongside aspirin, is one potential avenue of therapy. One such combination pill, PA32540, has undergone Phase I and Phase III trials and shows promising safety and efficacy results in these preliminary trials.
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Affiliation(s)
- Danielle Duffy
- Thomas Jefferson University, Philadelphia, PA 19107, USA
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Ramey K, Ma JD, Best BM, Atayee RS, Morello CM. Variability in metabolism of imipramine and desipramine using urinary excretion data. J Anal Toxicol 2014; 38:368-374. [PMID: 24782142 DOI: 10.1093/jat/bku034] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Variability in imipramine and desipramine metabolism was evaluated using urinary excretion data from patients with pain. Liquid chromatography-tandem mass spectrometry was used to quantitate concentrations in urine specimens. Interpatient population contained 600 unique imipramine specimens, whereas intrapatient population had 137 patients with two or more specimens. Normal concentration ranges of imipramine, desipramine and the desipramine/imipramine metabolic ratio (MR) were established, and various factors were tested for MR impact. Geometric mean of imipramine urine concentration was 0.46 mg/g of creatinine, and desipramine was 0.67 mg/g of creatinine. Gender, concomitant known CYP2C19 inhibitor use and urine pH did not affect MR. However, proton-pump inhibitor (PPI) users had a significantly lower mean MR than those without a listed PPI. Early age group (18-36 years) had a significantly higher mean MR than middle (37-66 years) and late (67-90 years) age groups. Approximately one-third were positive for one or more of hydrocodone, oxycodone, hydromorphone or oxymorphone. Patients with no opioids reported in the medication list had a significantly lower geometric mean MR than those with prescribed opioids (1.03 vs. 1.54, P = 0.004). Patients with only one prescribed opioid had a lower MR than those with two or more prescribed opioids. Patients with younger age, prescribed opioids and no listed PPI were more likely to have a higher geometric mean urinary desipramine/imipramine MR.
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Affiliation(s)
- Kelley Ramey
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA
| | - Joseph D Ma
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA Doris A. Howell Palliative Care Service, San Diego, CA, USA
| | - Brookie M Best
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA UCSD Department of Pediatrics, Rady Children's Hospital, San Diego, CA, USA
| | - Rabia S Atayee
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA Doris A. Howell Palliative Care Service, San Diego, CA, USA
| | - Candis M Morello
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA Diabetes Intense Medical Management Clinic, Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA
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9
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Cryer B, Mahaffey KW. Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment. J Multidiscip Healthc 2014; 7:137-46. [PMID: 24741318 PMCID: PMC3970722 DOI: 10.2147/jmdh.s54324] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Peptic ulcer disease is a major cause of morbidity and mortality in the US with more than six million diagnoses annually. Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI) bleeding and are often a clinical concern due to the widespread use of aspirin and nonsteroidal anti-inflammatory drugs, both of which have been shown to induce ulcer formation. The finding that Helicobacter pylori infection (independent of aspirin use) is associated with the development of ulcers led to a more thorough understanding of the causes and pathogenesis of ulcers and an improvement in therapeutic options. However, many patients infected with H. pylori are asymptomatic and remain undiagnosed. Complicating matters is a current lack of understanding of the association between aspirin use and asymptomatic ulcer formation. Low-dose aspirin prescriptions have increased, particularly for cardioprotection. Unfortunately, the GI side effects associated with aspirin therapy continue to be a major complication in both symptomatic and asymptomatic patients. These safety concerns should be important considerations in the decision to use aspirin and warrant further education. The medical community needs to continue to improve awareness of aspirin-induced GI bleeding to better equip physicians and improve care for patients requiring aspirin therapy.
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Affiliation(s)
- Byron Cryer
- University of Texas Southwestern Medical School, Dallas, TX, USA
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Bliden KP, Brener M, Gesheff MG, Franzese CJ, Tabrizchi A, Tantry U, Gurbel PA. PA tablets: investigational compounds combining aspirin and omeprazole for cardioprotection. Future Cardiol 2013; 9:785-97. [PMID: 24180537 DOI: 10.2217/fca.13.67] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
For most patients with prior cardiovascular events, preventing future secondary cardiovascular events requires life-long persistence with antiplatelet therapy. PA tablets (P: proton pump inhibitors; A: aspirin) are investigational compounds that were developed to provide the cardioprotective benefits of aspirin with the upper gastrointestinal protection of a proton pump inhibitor (e.g., omeprazole). The tablets are film-coated, coordinated-release tablets for oral administration that contain 40 mg immediate-release omeprazole and either 81 or 325 mg delayed-release aspirin. The goals of the clinical development program were to demonstrate the following: improved gastrointestinal safety of PA relative to enteric-coated aspirin alone; bioequivalence and comparative bioavailability between the PA compounds and currently marketed enteric-coated aspirin; and long-term safety. Two clinical pharmacology studies were also conducted to study the potential for interaction between PA32540 and clopidogrel.
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Affiliation(s)
- Kevin P Bliden
- Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA
| | - Michael Brener
- John Hopkins School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA
| | - Martin G Gesheff
- Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA
| | - Christopher J Franzese
- Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA
| | - Ali Tabrizchi
- Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA
| | - Udaya Tantry
- Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA
| | - Paul A Gurbel
- Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA
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Abstract
Proton pump inhibitors (PPI) and antiplatelet agents, especially aspirin and clopidogrel, are among the most prescribed medications worldwide. Their co-administration is justified by the increased risk of gastrointestinal bleeding related to the antiplatelet therapy. The issue of the interaction between PPI and clopidogrel has been raised with the emergence of the concept of "high on-clopidogrel platelet reactivity" (or "clopidogrel resistance") together with the discovery of the role of CYP2C19 isoform in the pharmacokinetics of those two medications. Indeed, CYP2C19 is involved in the conversion of the clopidogrel pro-drug into its active metabolite and is involved in the metabolisation of PPI into inactive metabolites, acting as substrates/inhibitors of CYP2C19. Despite their heterogeneity, most pharmacodynamic studies have shown a decreased clopidogrel antiplatelet effect when associated to PPI, especially those with the highest CYP2C19 inhibiting activity (omeprazole, lansoprazole, rabeprazole). On the other hand, clinical studies are inconclusive. Retrospective studies have shown an increased risk of major cardiovascular events or mortality when clopidogrel and PPI are associated in comparison with clopidogrel alone, particularly in the patients with the higher cardiovascular risk. However, the two prospective randomized studies published so far did not find any interaction and confirmed the benefit of PPI on the gastrointestinal bleeding. As a conclusion, as the clinical studies are not conclusive, the French health authorities have recently removed the alert about this interaction. PPI and clopidogrel can thus be co-prescribed.
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Affiliation(s)
- J Szymezak
- Laboratoire d'hématologie, hôpital Robert-Debré, CHU de Reims, France
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Macaione F, Montaina C, Evola S, Novo G, Novo S. Impact of dual antiplatelet therapy with proton pump inhibitors on the outcome of patients with acute coronary syndrome undergoing drug-eluting stent implantation. ISRN CARDIOLOGY 2012; 2012:692761. [PMID: 22792485 PMCID: PMC3391936 DOI: 10.5402/2012/692761] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2012] [Accepted: 05/07/2012] [Indexed: 12/29/2022]
Abstract
This study aimed to assess if proton pump inhibitors (PPIs) may reduce the effectiveness of clopidogrel, than H2 antagonist (anti-H2) in order to determine rehospitalization for acute coronary syndrome (re-ACS), target vessel revascularization (TVR) and cardiac death. This case-control study included 176 patients with ACS undergoing angioplasty (PCI) with drug-eluting stent implantation. The population was divided into two groups: PPI group (n = 121) consisting of patients receiving at discharge dual antiplatelet therapy (DAT) plus PPI and anti-H2 group (n = 55), consisting of patients receiving at discharge DAT + H2 receptor antagonist (H2RA). In a followup of 36 months the prevalence of ACS event (P = 0.014), TVR (P = 0.031) was higher in the PPI group than in the anti-H2 group; instead there was no statistically significant difference between groups for death. The variables independently associated with ACS were the diabetes, omeprazole, and esomeprazole; instead the variables independently associated with TVR were only omeprazole. Our data shows that the use of omeprazole and esomeprazole, with clopidogrel, is associated with increased risk of adverse outcomes after PCI with drug-eluting stent implantation.
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Affiliation(s)
- Francesca Macaione
- Division of Cardiology and Post-Graduate School of Cardiology, Center for the Early Diagnosis of Preclinical and Multifocal Atherosclerosis and for the Secondary Prevention, University Hospital “P. Giaccone” of the University of Palermo, 127-90127 Palermo, Italy
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Drepper MD, Spahr L, Frossard JL. Clopidogrel and proton pump inhibitors - where do we stand in 2012? World J Gastroenterol 2012; 18:2161-71. [PMID: 22611308 PMCID: PMC3351765 DOI: 10.3748/wjg.v18.i18.2161] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2011] [Revised: 02/20/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.
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