A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naïve Patients with Non-Valvular Atrial Fibrillation

PLoS One. 2015 Dec 28;10(12):e0145318. doi: 10.1371/journal.pone.0145318. eCollection 2015.

Abstract

Genotype-guided warfarin dosing have been proposed to improve patient’s management. This study is aimed to determine whether a CYP2C9- VKORC1- CYP4F2-based pharmacogenetic algorithm is superior to a standard, clinically adopted, pharmacodynamic method. Two-hundred naïve patients with non-valvular atrial fibrillation were randomized to trial arms and 180 completed the study. No significant differences were found in the number of out-of-range INRs (INR<2.0 or >3.0) (p = 0.79) and in the mean percentage of time spent in the therapeutic range (TTR) after 19 days in the pharmacogenetic (51.9%) and in the control arm (53.2%, p = 0.71). The percentage of time spent at INR>4.0 was significantly lower in the pharmacogenetic (0.7%) than in the control arm (1.8%) (p = 0.02). Genotype-guided warfarin dosing is not superior in overall anticoagulation control when compared to accurate clinical standard of care.

Trial registration: ClinicalTrials.gov NCT01178034.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation / drug therapy*
  • Cytochrome P-450 CYP2C9 / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytochrome P450 Family 4
  • Drug Monitoring / methods*
  • Female
  • Humans
  • International Normalized Ratio / methods
  • Male
  • Middle Aged
  • Pharmacogenetics / methods
  • Polymorphism, Single Nucleotide
  • Stroke / prevention & control
  • Treatment Outcome
  • Vitamin K Epoxide Reductases / metabolism
  • Warfarin / adverse effects
  • Warfarin / pharmacokinetics*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Warfarin
  • Cytochrome P-450 Enzyme System
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Cytochrome P450 Family 4
  • CYP4F2 protein, human
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases

Associated data

  • ClinicalTrials.gov/NCT01178034

Grants and funding

D. Bozzato was supported by the University of Padova (http://www.unipd.it/) Research Grant – protocol ID: CPDR111507. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.