Thromb Haemostasis
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Review Meta Analysis
Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. A systematic review and meta-analysis.
Variability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (primary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype-guided) VKA dosing algorithms in adults initiating anticoagulation. ⋯ Pre-specified exploratory analyses demonstrated that TTR was significantly higher when genotype-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41%; 95% CI 3.50,13.31; heterogeneity Χ(²)=15.18, p=0.01, I(²)=67%) but not when compared with clinical algorithm-guided dosing (4 trials, 1,770 patients: MD -0.29%; 95% CI -2.48,1.90; heterogeneity Χ(²)=1.53, p=0.68, I(²)=0%; p for interaction=0.002). In conclusion, genotype-guided compared with standard VKA dosing algorithms were not found to decrease a composite of death, thromboembolism and major bleeding, but did result in improved TTR. An improvement in TTR was observed in comparison with fixed VKA dosing algorithms, but not with clinical algorithms.