Effects on bleeding complications of pharmacogenetic testing for initial dosing of vitamin K antagonists: a systematic review and meta-analysis

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#adult #aged #anticoagulants #blood-coagulation #cytochrome-p-450-cyp2c9

Effects on bleeding complications of pharmacogenetic testing for initial dosing of vitamin K antagonists: a systematic review and meta-analysis

Franchini et al., 2014 | J Thromb Haemost | Meta Analysis

Citation

Franchini M, Mengoli C, ... Mannucci P M. Effects on bleeding complications of pharmacogenetic testing for initial dosing of vitamin K antagonists: a systematic review and meta-analysis. J Thromb Haemost. 2014-Sep;12(9):1480-7. doi:10.1111/jth.12647

Abstract

BACKGROUND: Although warfarin and other vitamin K antagonists (VKAs) are the most widely used oral anticoagulants for the prevention and treatment of thromboembolic events, a number of factors hamper their manageability, the most important being the inter-individual variability of the therapeutic dose requirement. Following the discovery of the influence of CYP2C9 and VKORC1 polymorphisms on VKA dose requirements, there has been interest in genotype-guided VKA dosing in order to reduce the risk of over-anticoagulation at the time of therapy initiation and hence the risk of bleeding, particularly prominent during the early days of treatment. To assess the impact on clinical outcomes of pharmacogenetic testing for initial VKA dosing, we have performed a systematic review and meta-analysis of the literature. METHODS: MEDLINE, EMBASE and Cochrane databases were searched up to March 2014. Only randomized controlled trials comparing genotype-guided vs. clinically-guided warfarin dosing were included. RESULTS: Nine trials including 2812 patients met the inclusion criteria and were pooled for meta-analytical evaluation. Risk of bias, assessed according to the Cochrane methodology, showed a low risk for the majority of domains analyzed in the included trials. A statistically significant reduction in the risk ratio (RR) for developing major bleeding events was observed in the pharmacogenetic-guided group compared with the control group (RR = 0.47; 95% CI, 0.23-0.96; P = 0.040). CONCLUSIONS: The results of this meta-analysis show that genotype-guided initial VKA dosing is able to reduce serious bleeding events by approximately 50% compared with clinically-guided dosing approaches.

Key Findings

Nine trials including 2812 patients met the inclusion criteria and were pooled for meta-analytical evaluation. Risk of bias, assessed according to the Cochrane methodology, showed a low risk for the majority of domains analyzed in the included trials. A statistically significant reduction in the risk ratio (RR) for developing major bleeding events was observed in the pharmacogenetic-guided group compared with the control group (RR = 0.47; 95% CI, 0.23-0.96; P = 0.040).

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 2812
Age Range See abstract
Condition See abstract

MeSH Terms

  • Adult
  • Aged
  • Anticoagulants
  • Blood Coagulation
  • Cytochrome P-450 CYP2C9
  • Female
  • Genotype
  • Hemorrhage
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Reproducibility of Results
  • Thromboembolism
  • Treatment Outcome
  • Vitamin K
  • Vitamin K Epoxide Reductases
  • Warfarin

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: vitamin-k

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09