Tracy Y. Wang, MD, MHS, MSc; Christopher B. Granger, MD
Are cytochrome P450(CYP)2C19 variant genotypes associated with clinical outcomes in patients with coronary artery disease who are receiving clopidogrel?
Included studies evaluated associations between reduced (*2 to *8) or increased (*17) function genetic variants of CYP2C19 and clinical outcomes in patients ≥ 18 years of age who had stable angina pectoris or an acute coronary syndrome and were receiving clopidogrel (scheduled loading dose ≥ 300 mg followed by 75 to 150 mg/d for ≥ 3 mo), had ≥ 30 days of follow-up, and provided absolute numbers of first occurrence of major adverse cardiovascular (CV) events (MACE) or fatal or nonfatal stent thrombosis.
MEDLINE, EMBASE/Excerpta Medica, and Cochrane Library (all to Dec 2010); relevant journals indexed in ISI Web of Science (2005 to 2010); and reference lists were searched for peer-reviewed observational studies or clinical trials. Studies published only as abstracts or conference reports were excluded. 15 studies (n = 28 368, mean age ≥ 60 y in 14 studies and 40 y in 1 study, 59% to 92% men) met the selection criteria: 4 randomized controlled trial substudies, 9 cohort studies, and 2 case–control or case–cohort studies. 14 studies evaluated ≥ 1 reduced function CYP2C19 genotype, and 5 evaluated an increased function genotype. Quality of combined evidence was low to very low for each comparison (Grading of Recommendations Assessment, Development, and Evaluation criteria).
Meta-analysis showed that reduced function genotypes were associated with increased risk for stent thrombosis (Table); this association was weaker in sensitivity analysis. Reduced function genotypes were not associated with MACE, and increased function genotypes were not associated with stent thrombosis or MACE (Table).
In patients with coronary artery disease who are receiving clopidogrel, reduced function CYP2C19 genotypes may be associated with increased risk for stent thrombosis. Neither reduced nor increased function genotypes are associated with major cardiovascular events.
*MACE = major adverse cardiovascular events; other abbreviations defined in Glossary. RRI, RRR, and CI calculated from random-effects summary odds ratios and noncarrier event rates reported in article.
Wang TY, Granger CB. Review: Reduced function CYP2C19 genotypes may increase risk for stent clots in patients receiving clopidogrel. Ann Intern Med. ;155:JC6–13. doi: 10.7326/0003-4819-155-12-201112200-02013
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Published: Ann Intern Med. 2011;155(12):JC6-13.
Cardiology, Coronary Heart Disease, Prevention/Screening.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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