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, 04/25/2012Park Y et al.
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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