Clinical benefits of pharmacogenetic algorithm-based warfarin dosing: meta-analysis of randomized controlled trials

- We conducted a meta-analysis to evaluate PG algorithm-based warfarin dosing.
- Risks for major bleeding and thromboembolic events were lower in PG-guided group.
- The benefits of PG algorithm were prominent in patients with longer follow-up time.
- Refined PG algorithm based warfarin dosing was more beneficial for patients.

BackgroundPharmacogenetic (PG) algorithms were proposed to predict warfarin therapeutic dose more accurately. However, the clinical efficacy of the strategy over the standard treatment was not consistently proven.MethodsWe conducted a meta-analysis of the published randomized controlled trials (RCTs) comparing PG algorithm-based warfarin dosing (PG group) with clinical or standard protocols (STD group). The PUBMED, EMBASE, Cochrane Library and Web of Science databases were searched up to June 2014.ResultsA total of 10 RCTs were retrieved for the meta-analysis with the inclusion of 2,601 participants. Primary analysis showed both major bleeding (2.65% versus 4.75%; RR: 0.57, 95% CI: 0.37- 0.90, P = 0.02) and thromboembolic events (0.59% versus 1.88%; RR: 0.38, 95% CI: 0.17-0.85, P = 0.02) were significantly lower in PG than in STD group. There was a trend towards increased percentage of time in therapeutic range (%TTR) [mean difference (MD): 4.65, 95% CI: 0.01- 9.29, P = 0.05] in PG group, but no difference was observed for over-anticoagulation (INR > 4). Subgroup analyses showed significant reduction of both major bleeding and thromboembolic events in PG group when the follow-up time was more than 1 month. After stratified by different PG algorithms, significant major bleeding reduction could be found in PG group when warfarin indication or co-medication of amiodarone was integrated in the algorithms.ConclusionPG algorithm-guided warfarin anticoagulation is beneficial for the reduction of both major bleeding and thromboembolic events compared with standard dosing strategy. The benefits may be prominent in patients with longer follow-up time, or guided by refined PG algorithms.