Objectives Warfarin is the most commonly used oral anticoagulant in the treatment and prevention of many thrombotic disorders. However, warfarin’s narrow therapeutic index and substantial interindividual variation make its dosing notoriously challenging. Until an individual’s therapeutic dose of warfarin is known, patients on warfarin therapy are at high risk for serious adverse health events, especially during drug initiation and when the international normalisation ratio (INR) is above and below the therapeutic target range. Our aim was to provide a pooled estimate of potential benefit from randomised controlled trials (RCTs) comparing genotype-based warfarin initiation model and dosing model without pharmocogenetic information.
Methods Relevant RCTs literature finished before Jan 2013 were searched through a number of digital databases including MEDLINE, EMBASE and CENTRAL. And then they were pooled by RevMan 5.0 and R 2.13.0 in three fields: international normalisation ratios (INR) time within target range, time to stable dose and occurrence rate of poor events. Pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated with the Mantel-Haenszel method and the fixed effects model.
Results Of 2496 articles identified, six studies with 1002 patients were included. Pooled estimates indicated shorten time to stable dose and a trend towards reduction in total bleeding event (OR: 0.42, 95%CI: 0.23-0.79;P = 0.0067) in the genotype-based warfarin initiation model group. No difference was noted in thromboembolic events and all-cause mortality.
Conclusions Genotype-based warfarin dosing method could optimise the quality of oral anticoagulant therapy (OAT) in the initiation period. The patients reach the stable dose more quickly, resulting in decreases in total bleeding events without a cost of increase of thromboembolic events.