Genotype-guided vitamin K antagonist dosing algorithms improve time in therapeutic range: A systematic review and meta-analysis

Introduction: Variability in vitamin K antagonist (VKA) dosing is partially explained by CYP2C9 and VKORC1 polymorphisms. Genotype-guided VKA dosing may improve quality of anticoagulation and outcomes. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding and improve time in therapeutic range (TTR). Methods: We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomized trials comparing genotype-guided and non genotype-guided VKA dosing algorithms in adults initiating anticoagulation. Data was extracted in duplicate and pooled using a random effects model. Results: We included 12 studies involving 3217 patients. Nine studies reported at least one of the components of the composite outcome (2483 patients, 94 events). Pooled data indicate that the relative risk for the composite outcome was similar in both groups (0.82; 95%CI 0.55,1.22) with no evidence of heterogeneity (×2=5.76, p=0.57, I2=0%). The genotype-guided group had higher TTR (mean difference 4.31; 95% CI 0.35,8.26; heterogeneity ×2=43.31, p