Genotype and cardiovascular risk with Clopidogrel

January 01, 0001

Genotype and cardiovascular risk with Clopidogrel

Clopidogrel is commonly prescribed following percutaneous intervention. There is a suggestion that its effectiveness varies based on genotype. These US, French, and German researchers sought to determine the cardiovascular risk among carriers of 1 ( 26% prevalence in whites) and 2 ( 2% prevalence in whites) reduced-function CYP2C19 genetic variants when treated with clopidogrel. MEDLINE, Cochrane Database of Systematic Reviews, and EMBASE were searched yielding 9 suitable studies.

The researchers found: "Among 9685 patients (91.3% who underwent percutaneous coronary intervention and 54.5% who had an acute coronary syndrome), 863 experienced the composite end point of cardiovascular death, myocardial infarction, or stroke, and 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were noncarriers, 26.3% had 1 reduced-function CYP2C19 allele, and 2.2% had 2 reduced-function CYP2C19 alleles. A significantly increased risk of the composite end point was evident in both carriers of 1 (HR, 1.55) and 2 (HR, 1.76) reduced-function CYP2C19 alleles, as compared with noncarriers. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of 1 (HR, 2.67) and 2 (HR, 3.97) CYP2C19 reduced-function alleles, as compared with noncarriers."

The researchers concluded: "Among patients treated with clopidogrel for percutaneous coronary intervention, carriage of even 1 reduced- function CYP2C19 allele appears to be associated with a significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis."

This study identifies by genotype a population of patients at increased cardiovascular risk when using Clopidogrel

For the full abstract, click here.

JAMA 304(16): 1821-1830, 27 October 2010
© 2010 American Medical Association
Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta- analysis. Jessica L. Mega, Tabassome Simon, Jean-Philippe Collet, et al.

Category: K. Circulatory. Keywords: clopidogrel, CYP2C19, genotype, cardiovascular risk, stent thrombosis, meta-analysis, journal watch.
Synopsis edited by Dr Paul Schaefer, Toledo, Ohio. Posted on Global Family Doctor 12 November 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.