Abstract 11847: 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<0.001, I2=79%). Prespecified exploratory analyses demonstrated that the approach for VKA dosing in the non genotype-guided group was a significant interaction term. The two approaches used were fixed dose (6 studies) versus clinical algorithm-guided dose (4 studies) (×2=10.07, p=0.002). TTR was significantly higher when genotype-guided dosing was compared with fixed VKA dosing (MD 8.41; 95% CI 3.50,13.31; heterogeneity ×2=15.18, p=0.01, I2=67%) but not when compared with clinical algorithm-guided dosing (MD -0.29; 95% CI -2.48,1.90; heterogeneity ×2=1.53, p=0.68, I2=0%).
Conclusions: Genotype-guided compared with non genotype-guided VKA dosing algorithms did not decrease a composite of death, thromboembolism and major bleeding but resulted in improved TTR. The improvement in TTR appeared to be isolated in the subgroup of studies using a fixed VKA dosing algorithm in the non genotype-guided group.
Author Disclosures: E.P. Belley-Côté: None. H. Hanif: None. F. D’Aragon: None. J. Eikelboom: Research Grant; Modest; Bayer, Boehringer-Ingelheim, Astra Zeneca, Bristol-Myer-Squibb,, Daiichi-Sankyo, Glaxo-Smith-Kline, Pfizer, Janssen, sanofi-aventis. Honoraria; Modest; Astra-Zeneca, Bayer ,, Boehringer-Ingelheim, Bristol-Myers Squibb, Pfizer, sanofi-aventis, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen. J.L. Anderson: None. M. Borgman: None. D.E. Jonas: None. S. Kimmel: Research Grant; Modest; NHLBI, Pfizer. A.H. Maitland-van der Zee: Research Grant; Significant; European Commission FP 7 Collaborative grant EU-PACT. M. Pirmohamed: Research Grant; Significant; EU Commission Framework 7 grant. R. Whitlock: None.
- © 2014 by American Heart Association, Inc.