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

Am Heart J. 2008 May;155(5):954-8. doi: 10.1016/j.ahj.2007.12.009. Epub 2008 Feb 19.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Atorvastatin
  • Clopidogrel
  • Cytochrome P-450 Enzyme System / physiology
  • Female
  • Heptanoic Acids / administration & dosage*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Pyrroles / administration & dosage*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome


  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors
  • Pyrroles
  • Cytochrome P-450 Enzyme System
  • Atorvastatin
  • Clopidogrel
  • Ticlopidine