Journal Article

High-dose atorvastatin does not negatively influence clinical outcomes among clopidogrel treated acute coronary syndrome patients—A Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) analysis

Murphy, Sabina A., Lotfi, Amir, Cannon, Christopher P., Giugliano, Gregory R., Schweiger, Marc J.

2008

Overview

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. 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. 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. In conclusion, the beneficial affects of atorvastatin 80 mg in reducing the primary end point at 2 years is independent of coadministration with clopidogrel.

• Publisher: Mosby, Inc,Elsevier,Elsevier Limited
• Subject: Acute Coronary Syndrome - drug therapy / Acute coronary syndromes / Aged / Atorvastatin Calcium / Biological and medical sciences / Cardiology. Vascular system / Cardiovascular / Cholesterol / Clinical outcomes / Coronary heart disease / Coronary vessels / Cytochrome P-450 Enzyme System - physiology / Drug therapy / Female / Heart / Heart attacks / Heptanoic Acids - administration & dosage / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage / Male / Medical sciences / Middle Aged / Myocarditis. Cardiomyopathies / Platelet Aggregation Inhibitors - administration & dosage / Pyrroles - administration & dosage / Ticlopidine - administration & dosage / Ticlopidine - analogs & derivatives / Treatment Outcome