Clinical Review

Journal of General Internal Medicine

, Volume 24, Issue 5, pp 656-664

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Genetic Testing Before Anticoagulation? A Systematic Review of Pharmacogenetic Dosing of Warfarin

  • Kirsten Neudoerffer KangelarisAffiliated withDivision of General Internal Medicine, University of CaliforniaDivision of Hospital Medicine, University of California Email author 
  • , Stephen BentAffiliated withDivision of General Internal Medicine, University of CaliforniaDivision of General Internal Medicine, Veterans Affairs Medical Center
  • , Robert L. NussbaumAffiliated withDivision of Medical Genetics, University of California
  • , David A. GarciaAffiliated withDepartment of Medicine, University of New Mexico
  • , Jeffrey A. TiceAffiliated withDivision of General Internal Medicine, University of California

Abstract

Background

Genotype-guided initial warfarin dosing may reduce over-anticoagulation and serious bleeding compared to a one-dose-fits-all dosing method.

Objective

The objective of this review was to investigate the safety and efficacy of genotype-guided dosing of warfarin in reducing the occurrence of serious bleeding events and over-anticoagulation.

Data Sources

The authors searched PubMed, EMBASE and International Pharmaceutical Abstracts through January 23, 2009, without language restrictions. Selected articles were randomized trials comparing pharmacogenetic dosing of warfarin versus a “standard” dose control algorithm in adult patients taking warfarin for the first time.

Review Methods

Two reviewers independently extracted data and assessed study quality using a validated instrument. The primary outcomes were major bleeding and time spent within the therapeutic range International Normalized Ratio (INR). Secondary outcomes included minor bleeding, thrombotic events and other measures of anticoagulation quality.

Results

Three of 2,014 studies (423 patients) met the inclusion and exclusion criteria. Differences in study quality, dosing algorithms, length of follow-up and outcome measures limited meta-analysis. Summary estimates revealed no statistically significant difference in bleeding rates or time within the therapeutic range INR. The highest quality study found no significant difference in primary or secondary outcomes, although there was a trend towards more rapid achievement of a stable dose (14.1 vs. 19.6 days, p = 0.07) in the pharmocogenetic arm.

Conclusions

We did not find sufficient evidence to support the use of pharmacogenetics to guide warfarin therapy. Additional clinical trials are needed to define the optimal approach to use warfarin pharmacogenetics in clinical practice.

KEY WORDS

warfarin pharmacogenetics CYP2C9 VKORC1 systematic review