Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
N Engl J Med. 2009 Feb 19;360(8):753-64. doi: 10.1056/NEJMoa0809329.

Estimation of the warfarin dose with clinical and pharmacogenetic data.

Erratum in

  • N Engl J Med. 2009 Oct 15;361(16):1613. Dosage error in article text.

Abstract

BACKGROUND:

Genetic variability among patients plays an important role in determining the dose of warfarin that should be used when oral anticoagulation is initiated, but practical methods of using genetic information have not been evaluated in a diverse and large population. We developed and used an algorithm for estimating the appropriate warfarin dose that is based on both clinical and genetic data from a broad population base.

METHODS:

Clinical and genetic data from 4043 patients were used to create a dose algorithm that was based on clinical variables only and an algorithm in which genetic information was added to the clinical variables. In a validation cohort of 1009 subjects, we evaluated the potential clinical value of each algorithm by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable therapeutic dose; we also evaluated other clinically relevant indicators.

RESULTS:

In the validation cohort, the pharmacogenetic algorithm accurately identified larger proportions of patients who required 21 mg of warfarin or less per week and of those who required 49 mg or more per week to achieve the target international normalized ratio than did the clinical algorithm (49.4% vs. 33.3%, P<0.001, among patients requiring < or = 21 mg per week; and 24.8% vs. 7.2%, P<0.001, among those requiring > or = 49 mg per week).

CONCLUSIONS:

The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach. The greatest benefits were observed in the 46.2% of the population that required 21 mg or less of warfarin per week or 49 mg or more per week for therapeutic anticoagulation.

2009 Massachusetts Medical Society

Comment in

PMID:
19228618
[PubMed - indexed for MEDLINE]
PMCID:
PMC2722908
Free PMC Article

Images from this publication.See all images (2)Free text

Figure 1
Figure 2

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Write to the Help Desk