Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study)

J Am Coll Cardiol. 2010 Jun 22;55(25):2804-12. doi: 10.1016/j.jacc.2010.03.009. Epub 2010 Apr 8.

Abstract

Objectives: This study was designed to determine whether genotype testing for patients initiating warfarin treatment will reduce the incidence of hospitalizations, including those due to bleeding or thromboembolism.

Background: Genotypic variations in CYP2C9 and VKORC1 have been shown to predict warfarin dosing, but no large-scale studies have prospectively evaluated the clinical effectiveness of genotyping in naturalistic settings across the U.S.

Methods: This national, prospective, comparative effectiveness study compared the 6-month incidence of hospitalization in patients receiving warfarin genotyping (n = 896) versus a matched historical control group (n = 2,688). To evaluate for temporal changes in the outcomes of warfarin treatment, a secondary analysis compared outcomes for 2 external control groups drawn from the same 2 time periods.

Results: Compared with the historical control group, the genotyped cohort had 31% fewer hospitalizations overall (adjusted hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58 to 0.82, p < 0.001) and 28% fewer hospitalizations for bleeding or thromboembolism (HR: 0.72, 95% CI: 0.53 to 0.97, p = 0.029) during the 6-month follow-up period. Findings from a per-protocol analysis were even stronger: 33% lower risk of all-cause hospitalization (HR: 0.67, 95% CI: 0.55 to 0.81, p < 0.001) and 43% lower risk of hospitalization for bleeding or thromboembolism (HR: 0.57, 95% CI: 0.39 to 0.83, p = 0.003) in patients who were genotyped. During the same period, there was no difference in outcomes between the 2 external control groups.

Conclusions: Warfarin genotyping reduced the risk of hospitalization in outpatients initiating warfarin. (The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings [MHSMayoWarf1]; NCT00830570).

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Case-Control Studies
  • Confidence Intervals
  • Cytochrome P-450 CYP2C9
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Genotype
  • Hemorrhage / chemically induced
  • Hemorrhage / genetics*
  • Hemorrhage / mortality
  • Hospitalization / statistics & numerical data*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics
  • Pharmacogenetics*
  • Probability
  • Proportional Hazards Models
  • Risk Assessment
  • Survival Analysis
  • Thromboembolism / chemically induced
  • Thromboembolism / genetics*
  • Thromboembolism / mortality
  • Treatment Outcome
  • Vitamin K Epoxide Reductases
  • Warfarin / adverse effects*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Warfarin
  • Mixed Function Oxygenases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases

Associated data

  • ClinicalTrials.gov/NCT00830570