Lack of Evidence of a Clopidogrel–Statin Interaction in the CHARISMA Trial
| Autor: | Deepak L. Bhatt, Koon-Hou Mak, Jacqueline Saw, Steven R. Steinhubl, Eric J. Topol, Keith A.A. Fox, Charisma Investigators, Danielle M. Brennan |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Ticlopidine Statin medicine.drug_class Atorvastatin Population Hemorrhage Placebo law.invention Cytochrome P-450 Enzyme System Double-Blind Method Randomized controlled trial law Internal medicine medicine Cytochrome P-450 CYP3A Humans Drug Interactions Pyrroles Prospective Studies cardiovascular diseases education Pravastatin education.field_of_study business.industry Middle Aged Clopidogrel Surgery Cardiovascular Diseases Heptanoic Acids Drug Therapy Combination Female Hydroxymethylglutaryl-CoA Reductase Inhibitors business Cardiology and Cardiovascular Medicine Platelet Aggregation Inhibitors Follow-Up Studies Fluvastatin medicine.drug |
| Zdroj: | Journal of the American College of Cardiology. 50(4):291-295 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2007.01.097 |
| Popis: | Objectives The purpose of this study was to evaluate the potential impact of clopidogrel and statin interaction in a randomized, placebo-controlled trial with long-term follow-up. Background There are conflicting data regarding whether statins predominantly metabolized by CYP3A4 reduce the metabolism of clopidogrel to its active metabolite and diminish its clinical efficacy. Methods The CHARISMA trial was a randomized trial comparing long-term 75 mg/day clopidogrel versus placebo in patients with cardiovascular disease or multiple risk factors on aspirin. The primary end point was a composite of myocardial infarction, stroke, or cardiovascular death at median follow-up of 28 months. We performed a secondary analysis evaluating the interaction of clopidogrel versus placebo with statin administration, categorizing baseline statin use to those predominantly CYP3A4 metabolized (atorvastatin, lovastatin, simvastatin; CYP3A4-MET) or others (pravastatin, fluvastatin; non–CYP3A4-MET). Results Of 15,603 patients enrolled, 10,078 received a statin at baseline (8,245 CYP3A4-MET, 1,748 non–CYP3A4-MET) and 5,496 did not. For the overall population, the primary end point was 6.8% with clopidogrel and 7.3% with placebo (hazard ratio [HR] 0.93; p = 0.22). This was similar among patients on CYP3A4-MET (5.9% clopidogrel, 6.6% placebo, HR 0.89; p = 0.18) or non–CYP3A4-MET statin (5.7% clopidogrel, 7.2% placebo, HR 0.78; p = 0.19). There was no interaction between statin types and randomized treatment (p = 0.69). Patients on atorvastatin (n = 4,127) (5.7% clopidogrel, 7.1% placebo, HR 0.80; p = 0.06) or pravastatin (n = 1,440) (5.1% clopidogrel, 7.0% placebo, HR 0.72; p = 0.13) had similar event rates. Conclusions Despite theoretic concerns and ex vivo testing suggesting a potential negative interaction with concomitant clopidogrel and CYP3A4-MET statin administration, there was no evidence of an interaction clinically in a large placebo-controlled trial with long-term follow-up. |
| Databáze: | OpenAIRE |
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