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Interaction of clopidogrel and statins in secondary prevention after cerebral ischaemia - a randomized, double-blind,

Timo Siepmann1, Denise Heinke, Jessica Kepplinger

  • 1Department of Neurology, Dresden University of Technology, Dresden, Germany.

British Journal of Clinical Pharmacology
|May 8, 2014
PubMed

Insights

Simvastatin, metabolized by CYP3A4, does not affect clopidogrel

Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Clinical Trials

Background:

  • Variability in clopidogrel response impacts secondary prevention after cerebral ischemia.
  • This variability may stem from competitive metabolism between clopidogrel and CYP3A4-metabolized statins like simvastatin.

Purpose of the Study:

  • To test if simvastatin reduces clopidogrel's antiplatelet effect.
  • To compare simvastatin (CYP3A4 substrate) with fluvastatin (CYP2C9 substrate) regarding their interaction with clopidogrel.

Main Methods:

  • A randomized, double-blind, crossover study in 13 cerebral ischemia patients.
  • Patients received clopidogrel with either simvastatin or fluvastatin for 14 days, followed by a crossover.
  • Assessed platelet aggregation, clopidogrel active metabolite (CAM) levels, and prothrombin time (PT).

Main Results:

  • Clopidogrel effectively reduced platelet aggregation in all patients.
  • Neither simvastatin nor fluvastatin altered platelet aggregation or CAM levels.
  • Simvastatin, but not fluvastatin, decreased PT Quick percent value when co-administered with clopidogrel.

Conclusions:

  • Simvastatin co-administration does not impair clopidogrel's inhibition of platelet aggregation.
  • A decrease in PT Quick percent value with simvastatin and clopidogrel may relate to reduced prothrombin fragment 1+2 activity.
Abstract

Keywords:
CYP 3A4clopidogrelfluvastatinplatelet aggregationsimvastatin

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