BACKGROUND:Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Unlike pravastatin, atorvastatin is a statin that is subject to metabolism by cytochrome P-450-3A4, and drug-drug interactions with other potent inhibitors of this cytochrome system have been demonstrated. However, the clinical impact of this interaction has created debate. METHODS: In the PROVE IT-TIMI 22 study, 4162 patients with an acute coronary syndrome within the preceding 10 days were randomly assigned in a 1:1 fashion to pravastatin 40 mg or atorvastatin 80 mg daily. The primary efficacy outcome measure was the time from randomization until the first occurrence of a component of the primary end point: death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, or stroke. RESULTS: At 30 days, there was a trend for less occurrence of the primary end point in patients randomized to atorvastatin compared with pravastatin, irrespective of whether they were taking clopidogrel. This becomes significant at 2-year follow-up in clopidogrel-treated patients (21.66 % vs 26.18% P = .0091). There was no evidence of interaction in the clopidogrel/no clopidogrel subgroup for the primary end point (interaction P = .65) or the components of the composite. CONCLUSION: In conclusion, the beneficial affects of atorvastatin 80 mg in reducing the primary end point at 2 years is independent of coadministration with clopidogrel.
RCT Entities:
BACKGROUND:Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Unlike pravastatin, atorvastatin is a statin that is subject to metabolism by cytochrome P-450-3A4, and drug-drug interactions with other potent inhibitors of this cytochrome system have been demonstrated. However, the clinical impact of this interaction has created debate. METHODS: In the PROVE IT-TIMI 22 study, 4162 patients with an acute coronary syndrome within the preceding 10 days were randomly assigned in a 1:1 fashion to pravastatin 40 mg or atorvastatin 80 mg daily. The primary efficacy outcome measure was the time from randomization until the first occurrence of a component of the primary end point: death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, or stroke. RESULTS: At 30 days, there was a trend for less occurrence of the primary end point in patients randomized to atorvastatin compared with pravastatin, irrespective of whether they were taking clopidogrel. This becomes significant at 2-year follow-up in clopidogrel-treated patients (21.66 % vs 26.18% P = .0091). There was no evidence of interaction in the clopidogrel/no clopidogrel subgroup for the primary end point (interaction P = .65) or the components of the composite. CONCLUSION: In conclusion, the beneficial affects of atorvastatin 80 mg in reducing the primary end point at 2 years is independent of coadministration with clopidogrel.
Authors: Morten Schmidt; Martin B Johansen; Michael Maeng; Anne Kaltoft; Lisette O Jensen; Hans-Henrik Tilsted; Hans E Bøtker; John A Baron; Henrik Toft Sørensen Journal: Br J Clin Pharmacol Date: 2012-07 Impact factor: 4.335
Authors: Michael N Zairis; George Z Tsiaousis; Nikolaos G Patsourakos; Anastassios Theodossis Georgilas; Constantinos F Kontos; Evdokia N Adamopoulou; Konstantinos Vogiatzidis; Spyros K Argyrakis; Constantine N Fakiolas; Stefanos G Foussas Journal: Can J Cardiol Date: 2010-02 Impact factor: 5.223