Key result
Variant CYP2C9 genotypes were associated with 19.6% to 78.1% lower warfarin dose requirements compared to the wild-type CYP2C9*1/*1 genotype.
Why the study?
Do variant CYP2C9 genotypes reduce warfarin dose requirements compared to the wild-type genotype in patients taking warfarin?
Meta-Analysis (n=7,907)
Do variant CYP2C9 genotypes reduce warfarin dose requirements compared to the wild-type genotype in patients taking warfarin?
Effect estimate: 19.6% to 78.1% lower dose requirement
Variant CYP2C9 genotypes are associated with a quantifiable, stepwise reduction in warfarin dose requirements compared to the wild-type genotype.
Variant CYP2C9 genotypes warrant reduced initial warfarin doses; extends meta-analytic support for genotype-guided algorithms.
PURPOSE: To quantify the influence of common cytochrome P450 2C9 (CYP2C9) polymorphisms on warfarin dose requirements. METHODS: A systematic review and a meta-analysis, calculating the warfarin dose reduction associated with the five most common variant CYP2C9 genotypes. RESULTS: Thirty-nine studies (7,907 patients) were included in the meta-analysis. Compared to the CYP2C9*1/*1 genotype, the CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3, and CYP2C9*3/*3 required warfarin doses that were 19.6 (95% confidence interval 17.4, 21.9), 33.7 (29.4, 38.1), 36.0 (29.9, 42.0), 56.7 (49.1, 64.3), and 78.1% (72.0, 84.3) lower, respectively. The impact of CYP2C9 genotype tended to be larger in patients without interacting drugs. CONCLUSIONS: Previous studies have rarely been powered to determine the quantitative influence of specific CYP2C9 genotypes on warfarin dose requirements. The results from our pooled analysis are likely to be the most accurate to date and the methodology could serve as a model for future pharmacogenetic meta-analyses.
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Lindh et al. (2008) conducted a meta-analysis in Patients requiring warfarin therapy (n=7,907). Variant CYP2C9 genotypes (*1/*2, *1/*3, *2/*2, *2/*3, *3/*3) vs. CYP2C9*1/*1 genotype was evaluated on Warfarin dose reduction (19.6% to 78.1% lower dose requirement). Variant CYP2C9 genotypes were associated with 19.6% to 78.1% lower warfarin dose requirements compared to the wild-type CYP2C9*1/*1 genotype.
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