title: Simultaneous administration of high-dose atorvastatin and clopidogrel does not interfere with platelet inhibition during percutaneous coronary intervention.
abstract: BACKGROUND
  Reloading with high-dose atorvastatin shortly before percutaneous coronary interventions (PCIs) has been proposed as a strategy to reduce periprocedural myonecrosis. There has been a concern that statins that are metabolized by cytochrome P450 3A4 may interfere with clopidogrel metabolism at high doses. The impact of simultaneous administration of high doses of atorvastatin and clopidogrel on the efficacy of platelet inhibition has not been established.
  
  
  METHODS
  Subjects (n=60) were randomized to receive atorvastatin 80 mg together with clopidogrel 600 mg loading dose (n=28) versus clopidogrel 600 mg alone (n=32) at the time of PCI. Platelet aggregation was measured at baseline, 4 hours after clopidogrel loading dose, and 16-24 hours after clopidogrel loading dose by light transmittance aggregometry using adenosine diphosphate as agonist.
  
  
  RESULTS
  Platelet aggregation was similar at baseline in both the atorvastatin and the control groups (adenosine diphosphate 10 µM: 57%±19% vs 61%±21%; P=0.52). There was no significant difference in platelet aggregation between the atorvastatin and the control groups at 4 hours (37%±18% vs 39%±21%; P=0.72) and 16-24 hours post-clopidogrel loading dose (35%±17% vs 37%±18%; P=0.75). No significant difference in incidence of periprocedural myonecrosis was observed between the atorvastatin and control groups (odds ratio: 1.02; 95% confidence interval 0.37-2.8).
  
  
  CONCLUSIONS
  High-dose atorvastatin given simultaneously with clopidogrel loading dose at the time of PCI does not significantly alter platelet inhibition by clopidogrel. Statin reloading with high doses of atorvastatin at the time of PCI appears to be safe without adverse effects on platelet inhibition by clopidogrel (ClinicalTrials.gov: NCT00979940).
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Rolf P
authors.initials: RP
authors.lastname: Kreutz
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Breall
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Anjan
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: von der Lohe
authors.affiliation: Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kovacs
authors.affiliation: Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
keywords: atorvastatin; clopidogrel; myocardial infarction; percutaneous coronary intervention; platelet aggregation