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1. Eur Heart J. 2012 Apr 16. [Epub ahead of print]

Accelerated platelet inhibition by switching from atorvastatin to a
non-CYP3A4-metabolized statin in patients with high platelet reactivity

Park Y, Jeong YH, Tantry US, Ahn JH, Kwon TJ, Park JR, Hwang SJ, Gho EH, Bliden
KP, Kwak CH, Hwang JY, Kim S, Gurbel PA.

Division of Cardiology, Department of Internal Medicine, Gyeongsang National
University Hospital, Jinju, Korea.

AimsCYP3A4-metabolized statins can influence the pharmacodynamic effect of
clopidogrel. We sought to assess the impact of switching to a
non-CYP3A4-metabolized statin on platelet function among patients receiving
clopidogrel and atorvastatin with high on-treatment platelet reactivity
(HPR).Methods and resultsPercutaneous 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. Fifty-two 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.ConclusionsAmong PCI-treated patients with 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.

PMID: 22507978 [PubMed - as supplied by publisher]