Do CYP2C19 gene polymorphisms alter the efficacy of clopidogrel

January 01, 0001

Do CYP2C19 gene polymorphisms alter the efficacy of clopidogrel

These German, Dutch, and US researchers examined the effect of cytochrome P450 (CYP) 2C19 genotype variants on clopidogrel’s clinical effects. They performed a systematic review and meta-analysis of Medline, Embase, the Cochrane Library, online databases, contents pages and bibliographies for studies measuring cardiovascular events or stent thrombosis in patients with various CYP2C19 loss of function or gain of function alleles. Fifteen studies met inclusion criteria.

The researchers found: "The random effects summary odds ratio for stent thrombosis in carriers of at least one CYP2C19 loss of function allele versus non-carriers combining nine studies was 1.77. This nominally significant odds ratio was subject to considerable bias across the studies (small study effect bias and replication diversity). The adjustment for these quality modifiers tended to abolish the association. The corresponding random effects summary odds ratio of major adverse cardiovascular events for 12 studies combined was 1.11. The random effects summary odds ratio of stent thrombosis in carriers versus non-carriers of at least one CYP2C19*17 gain of function allele for three studies combined was 0.99, and the corresponding odds ratio of major adverse cardiovascular events in five studies was 0.93. The overall quality of epidemiological evidence was graded as low, which excludes reliable clinical assessments."

The researchers concluded: "Accumulated information from genetic association studies does not indicate a substantial or consistent influence of CYP2C19 gene polymorphisms on the clinical efficacy of clopidogrel. The current evidence does not support the use of individualised antiplatelet regimens guided by CYP2C19 genotype."

This meta-analysis does not find consistent effects of CYP2C19 alleles on the functioning of clopidogrel, although further study is warranted.

For the full abstract, click here.

BMJ 343:d4588, 4 August 2011 © 2011 BMJ Publishing Group Ltd.
Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis. Tim Bauer, Heleen J Bouman, Jochem W van Werkum, Neville F Ford, Jurriën M ten Berg, Dirk Taubert. Correspondence to D Taubert: [email protected]

Category: B. Blood/Immune Mechanisms. Keywords: clopidogrel, CYP2C19, polymorphisms, cardiovascular risk, stent thrombosis, systematic review with meta-analysis, journal watch.
Synopsis edited by Dr Paul Schaefer, Toledo, Ohio. Posted on Global Family Doctor 2 September 2011

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

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