title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Division of Cardiology, Baystate Medical Center, Springfield, MA 01199, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Lotfi
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Schweiger
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Giugliano
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D000069059:Atorvastatin; D000077144:Clopidogrel; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D003577:Cytochrome P-450 Enzyme System; D000069059:Atorvastatin; D000077144:Clopidogrel; D013988:Ticlopidine