Meta-analysis of Randomized Controlled Trials of Genotype-guided versus Standard Dosing of Warfarin.
Chest. 2015 Mar 26;
Authors: Dahal K, Sharma SP, Fung E, Lee J, Moore JH, Unterborn JN, Williams SM
Introduction: Warfarin is widely prescribed anticoagulant and its effect depends on various patient factors including genotypes. Randomized controlled trials (RCTs) comparing genotype-guided dosing (GD) of warfarin with standard dosing (SD) have shown mixed efficacy and safety outcomes. We performed a meta-analysis of all published RCTs comparing GD versus SD in adult patients with various indications of warfarin use.
Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL and relevant references for English language RCTs (inception through March 2014). We performed the meta-analysis using random effects model.
Results: 10 RCTs with a total of 2505 patients were included in the meta-analysis. GD compared to SD resulted in similar % time in therapeutic range (TTR) at ≤1 month follow-up [44% vs. 44.5%, mean difference (MD): -0.52, 95% confidence interval (CI): (-3.15-2.10), P=0.70] and higher %TTR [62.9% vs. 56.6%, MD: 6.35 (1.76-10.95), p= 0.007] at >1 month follow up, a trend towards lower risk of major bleeding [risk ratio (RR): 0.46 (0.19-0.1.11) , p= 0.08] at ≤1 month follow-up and lower risks of major bleeding [0.34 (0.16-0.74), p= 0.006] at >1-month follow-up, and shorter time to maintenance dose (TMD) [23 days vs. 33 days, MD: -9.54 days (-18.10, -0.98), P=0.03] at follow-up but had no effects on INR > 4.0, non-major bleeding, thrombotic outcomes or overall mortality.
Conclusion: In the first month of genotype-guided warfarin therapy, compared to standard dosing, there were no improvements in %TTR, INR > 4.0, major or minor bleeding, thromboembolism, or all-cause mortality. There was shorter TMD, and after one month, improved %TTR and major bleeding incidence, making this a cost-effective strategy in patients requiring longer anticoagulation.
PMID: 25811981 [PubMed - as supplied by publisher]