Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin

Khagendra Dahal, Sharan P. Sharma, Erik Fung, Juyong Lee, Jason H. Moore, John N. Unterborn, Scott M. Williams
2015 Chest  
BACKGROUND: Warfarin is a widely prescribed anticoagulant, and its eff ect depends on various patient factors including genotypes. Randomized controlled trials (RCTs) comparing genotypeguided dosing (GD) of warfarin with standard dosing have shown mixed effi cacy and safety outcomes. We performed a meta-analysis of all published RCTs comparing GD vs standard dosing in adult patients with various indications of warfarin use. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of
more » ... olled Trials (CENTRAL), and relevant references for English language RCTs (inception through March 2014). We performed the meta-analysis using a random eff ects model. RESULTS: Ten RCTs with a total of 2,505 patients were included in the meta-analysis. GD compared with standard dosing resulted in a similar % time in therapeutic range (TTR) at Յ 1 month follow-up (39.7% vs 40.2%; mean diff erence [MD], 2 0.52 [95% CI, 2 3.15 to 2.10]; P 5 .70) and higher % TTR (59.4% vs 53%; MD, 6.35 [95% CI, 1.76-10.95]; P 5 .007) at . 1 month follow-up, a trend toward lower risk of major bleeding (risk ratio, 0.46 [95% CI, 0.19-0.1.11]; P 5 .08) at Յ 1 month follow-up and lower risks of major bleeding (0.34 [95% CI, 0.16-0.74], P 5 .006) at . 1-month follow-up, and shorter time to maintenance dose (TMD) (24.6 days vs 34.1 days; MD, 2 9.54 days [95% CI, 2 18.10 to 2 0.98]; P 5 .03) at follow-up but had no eff ects on international normalized ratio [INR] . 4.0, nonmajor bleeding, thrombotic outcomes, or overall mortality. CONCLUSIONS: In the fi rst month of genotype-guided warfarin therapy, compared with standard dosing, there were no improvements in % TTR, INR . 4.0, major or minor bleeding, thromboembolism, or all-cause mortality. Th ere was a shorter TMD, and, aft er 1 month, improved % TTR and major bleeding incidence, making this a cost-eff ective strategy in patients requiring longer anticoagulation therapy. ABBREVIATIONS: GD 5 genotype-guided dosing; HR 5 hazard ratio; INR 5 international normalized ratio; MD 5 mean diff erence; RCT 5 randomized controlled trial; RR 5 risk ratio; TMD 5 time to maintenance dose; TTR 5 time in therapeutic range
doi:10.1378/chest.14-2947 pmid:25811981 pmcid:PMC4556123 fatcat:uhikcl5mdreqxiyxg3clrbenaq