A randomized comparison of platelet reactivity in patients after treatment with various commercial clopidogrel preparations: The CLO-CLO trial

Oberhänsli, Markus; Lehner, C.; Puricel, Serban; Lehmann, S.; Togni, Mario; Stauffer, Jean‐Christophe; Baeriswyl, Gérard; Goy, Jean‐Jácques; Cook, Stéphane

doi:10.1016/j.acvd.2012.06.001

Cited by 8 publications

(6 citation statements)

References 18 publications

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“…38 reports were excluded because only bioequivalence outcomes were reported or relevant outcome data could not be extracted. We attempted to contact all investigators, and thanks to their answers we were able to retrieve four additional trials [ 72 , 73 , 78 , 81 ], and to add the data on mild/moderate [ 83 ] or serious [ 75 ] adverse events for two studies. The complete list of the excluded trials is available in Additional Appendix S2.…”

Section: Resultsmentioning

confidence: 99%

Generic versus brand-name drugs used in cardiovascular diseases

et al. 2015

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This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI −0.05; 0.08) for soft outcomes; −0.06 (−0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (−0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40–7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-015-0104-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Generic versus brand-name drugs used in cardiovascular diseases

et al. 2015

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“…Several previous studies have tested the bioequivalence of new generic clopidogrel against Plavix ® tablets 3 , 17 , 18 or the antiplatelet effect of other salts. 5 , 19 The aim of this study was to test the bioavailability of new generic clopidogrel 75 mg tablet versus the reference Plavix. The two dosage forms were administered to 38 fasting volunteers in order to eliminate the influence of food on drug absorption.…”

Section: Discussionmentioning

confidence: 99%

“…Several commercial preparations are available now, and it is of critical importance to demonstrate that these preparations are bioequivalent and have similar inhibition of platelet reactivity. 5 During the development of new generic formulations, the formulators try to adhere to the same excipients used in the brand product and the manufacturing process as much as they can to minimize problems with stability. However, it is important to conduct an in vivo study to find any difference between the generic product and the original brand in terms of safety and clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro–in vivo correlation

Zaid¹,

Al-Ramahi²,

Bustami³

et al. 2015

DDDT

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ObjectiveThe aim of this study was to evaluate the bioequivalence of two drug products, generic clopidogrel bisulfate 75 mg film-coated tablets versus the reference Plavix® clopidogrel bisulfate 75 mg film-coated tablets.MethodsBioequivalence of tablets was tested by comparisons against the reference brand product in accordance with the requirements of the Declaration of Helsinki, the current Good Clinical Practice Guidelines, and the International Conference on Harmonization.ResultsThe relationship between concentration and peak area ratio was found to be linear within the range 24.500–1,836.600 pg/mL for clopidogrel. The correlation coefficient (r) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. The point estimates (ratios of geometric mean) were 104.122%, 104.184%, and 109.091% for areas under the plasma concentration–time curve (AUC) AUC0-last, AUC0-∞, and peak plasma concentration Cmax, respectively. These pharmacokinetic parameter values of clopidogrel and its main metabolite lie within the bioequivalence limit (80%–125%) specified by the US Food and Drug Administration and the European Medicines Agency.ConclusionThe tested drug product was bioequivalent to the reference drug under fasting conditions and had the same safety profile, which is important to achieve equivalent therapeutic effect with the reference.

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“…Besides, a number of bioequivalence studies, including studies from East Asia, 36,37 were conducted on various generic clopidogrel versus brand-name clopidogrel to evaluate their efficacy in platelet aggregation inhibition and no significant difference was observed, suggesting generic clopidogrel and brand-name clopidogrel have comparable antiplatelet effects. [38][39][40] Overall, the prescription rate of generic clopidogrel was relatively low in this study, and it was more often prescribed 12 months after the AMI episode, presumably when the physician considered the patient to be more stable and only requiring a single antiplatelet agent. The use of generic medications has increased rapidly over the past 20 years, however about one-third of patients, physicians, and pharmacists are still skeptical about the safety, effectiveness, and quality of generic medications.…”

Section: Discussionmentioning

confidence: 85%

Clinical outcomes of generic versus brand‐name clopidogrel for secondary prevention in patients with acute myocardial infarction: A nationwide cohort study

Chan

Tung

Lee

et al. 2023

Clinical Translational Sci

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Skepticism exists among healthcare workers and patients regarding the efficacy and safety of generic medication, despite its potential to lower healthcare costs. This study aimed to compare the outcomes of a generic clopidogrel and its brand‐name counterpart for secondary prevention in patients with acute myocardial infarction (AMI). Using the Taiwan National Health Insurance Research Database, we identified 49,325 patients who were hospitalized for AMI between January 1, 2008 and December 31, 2013 and prescribed either generic or brand‐name clopidogrel. Among them, 2419 (4.9%) were prescribed the generic clopidogrel. After propensity score matching, both the generic and brand‐name groups consisted of 2382 patients. The primary efficacy outcome was a composite of myocardial infarction, coronary revascularization, ischemic stroke, and all‐cause death. The primary safety outcome was major bleeding requiring hospitalization. At a mean follow‐up of 2.5 years, the generic and brand‐name clopidogrel groups had comparable risks of primary efficacy outcome (41.9% vs. 42%; hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.88–1.04), and the risks of the individual components were also similar. There were no significant differences between the two groups in major bleeding (7.9% vs. 7.9%; HR 0.99; 95% CI 0.81–1.21). Subgroup analyses also revealed no statistically significant interactions between the treatment effect and various subgroups. In this retrospective database analysis, the generic clopidogrel was comparable to its brand‐name counterpart regarding cardiovascular and bleeding outcomes for the treatment of patients with AMI.

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A randomized comparison of platelet reactivity in patients after treatment with various commercial clopidogrel preparations: The CLO-CLO trial

Abstract: Generic clopidogrel preparations provided similar inhibition of platelet reactivity to original clopidogrel bisulphate, although prasugrel was more efficient.

Cited by 8 publications

References 18 publications

Generic versus brand-name drugs used in cardiovascular diseases

Generic versus brand-name drugs used in cardiovascular diseases

Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro–in vivo correlation

Clinical outcomes of generic versus brand‐name clopidogrel for secondary prevention in patients with acute myocardial infarction: A nationwide cohort study

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A randomized comparison of platelet reactivity in patients after treatment with various commercial clopidogrel preparations: The CLO-CLO trial

Abstract: Generic clopidogrel preparations provided similar inhibition of platelet reactivity to original clopidogrel bisulphate, although prasugrel was more efficient.

Cited by 8 publications

References 18 publications

Generic versus brand-name drugs used in cardiovascular diseases

Generic versus brand-name drugs used in cardiovascular diseases

Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro&ndash;in vivo correlation

Clinical outcomes of generic versus brand‐name clopidogrel for secondary prevention in patients with acute myocardial infarction: A nationwide cohort study

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Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro–in vivo correlation