Accelerated platelet inhibition by switching from atorvastatin to a non-CYP3A4-metabolized statin in patients with high platelet reactivity (ACCEL-STATIN) study

European Heart Journal, 04/25/2012

Among PCI–treated patients with high on–treatment platelet reactivity (HPR) during co–administration of clopidogrel and atorvastatin, switching to a non–CYP3A4–metabolized statin can significantly decrease platelet reactivity and the prevalence of HPR. This switching effect appears similar irrespective of the type of non–CYP3A4–metabolized statin.


  • Percutaneous coronary intervention (PCI)–treated patients (n= 50) with HPR [20 μM adenosine diphosphate (ADP)–induced maximal platelet aggregation (MPA) >50%] were enrolled during chronic administration of atorvastatin (10 mg/day) and clopidogrel (75 mg/day) (≥6 months).
  • They were randomly assigned to a 15–day therapy with either rosuvastatin 10 mg/day (n= 25) or pravastatin 20 mg/day (n= 25).
  • Platelet function was assessed before and after switching by conventional aggregometry and the VerifyNow P2Y12 assay.
  • Genotyping was performed for CYP2C19*2/*3, CYP3A5*3, and ABCB1 C3435T alleles.
  • The primary endpoint was the absolute change in 20 μM ADP–induced MPA.


  • After switching, MPAs after stimuli with 20 and 5 μM ADP were decreased by 6.6% (95% confidence interval: 3.2–10.1%; P < 0.001), and 6.3% (95% confidence interval: 2.5–10.2%; P = 0.002), respectively.
  • 52 P2Y12 reaction units fell (95% confidence interval: 35–70; P < 0.001) and the prevalence of HPR decreased (24%; P < 0.001).
  • Pharmacodynamic effects were similar after rosuvastatin and pravastatin therapy.
  • In addition to smoking status, the combination of calcium channel blocker usage and ABCB1 C3435T genotype significantly affected the change of 20 μM ADP–induced MPA.

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