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

Yongwhi Park, Young Hoon Jeong, Udaya S. Tantry, Jong Hwa Ahn, Tae Jung Kwon, Jeong Rang Park, Seok Jae Hwang, Eun Ha Gho, Kevin P. Bliden, Choong Hwan Kwak, Jin Yong Hwang, Sunjoo Kim, Paul A. Gurbel

Research output: Contribution to journalArticlepeer-review

Abstract

Aims CYP3A4-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: 3.210.1; P < 0.001), and 6.3 (95 confidence interval: 2.510.2; P = 0.002), respectively. Fifty-two P2Y12 reaction units fell (95 confidence interval: 3570; 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. Conclusions Among 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.

Original languageEnglish (US)
Pages (from-to)2151-2162
Number of pages12
JournalEuropean heart journal
Volume33
Issue number17
DOIs
StatePublished - Sep 1 2012

Keywords

  • Atorvastatin
  • Clopidogrel
  • High platelet reactivity
  • Non-CYP3A4-metabolized statin
  • Platelet

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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