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Warfarin pharmacogenomics: current best evidence.

¹Department of Medicine and Department of Biostatistics and Epidemiology, Perelman University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Journal of Thrombosis and Haemostasis : JTH

|July 8, 2015

Summary

Genetic information improves warfarin dosing compared to fixed doses, but not when added to clinical information alone. Pharmacogenetic algorithms enhance anticoagulation control over fixed dosing strategies.

Keywords:

drug therapy genetics pharmacogenetics randomized controlled trials as topic warfarin

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Area of Science:

Pharmacogenomics
Clinical Pharmacology
Anticoagulation Therapy

Background:

The role of genetic information in guiding warfarin dosing remains debated.
Previous studies yielded conflicting results on the utility of pharmacogenetic-guided anticoagulation.

Purpose of the Study:

To evaluate the incremental benefit of genetic information in warfarin dosing strategies.
To compare pharmacogenetic algorithms with standard clinical dosing and fixed dosing.

Main Methods:

Analysis of recent large clinical trials (COAG, EU-PACT UK) investigating pharmacogenetic dosing of warfarin, acenocoumarol, and phenprocoumon.
Comparison of pharmacogenetic-based dosing algorithms against clinical information-based dosing and fixed-dose strategies.

Main Results:

The COAG and acenocoumarol/phenprocoumon studies showed no incremental benefit of adding genetic information to clinical information.
The EU-PACT UK trial demonstrated improved outcomes with a pharmacogenetic algorithm compared to fixed dosing.
Pharmacogenetic algorithms, not just genetic information added to clinical data, showed improved anticoagulation control.

Conclusions:

Current evidence does not support adding genetic information to clinical data for improved anticoagulation control.
Pharmacogenetic algorithms offer an advantage over fixed dosing strategies for anticoagulation management.