Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2015 Sep;148(3):701-710.
doi: 10.1378/chest.14-2947.

Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin

Khagendra Dahal  1 , Sharan P Sharma  2 , Erik Fung  3 , Juyong Lee  4 , Jason H Moore  5 , John N Unterborn  6 , Scott M Williams  7
Affiliations
Meta-Analysis

Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin

Khagendra Dahal et al. Chest. 2015 Sep.

Abstract

Background: Warfarin is a widely prescribed anticoagulant, and its effect depends on various patient factors including genotypes. Randomized controlled trials (RCTs) comparing genotype-guided dosing (GD) of warfarin with standard dosing have shown mixed efficacy and safety outcomes. We performed a meta-analysis of all published RCTs comparing GD vs standard dosing in adult patients with various indications of warfarin use.

Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and relevant references for English language RCTs (inception through March 2014). We performed the meta-analysis using a random effects model.

Results: Ten RCTs with a total of 2,505 patients were included in the meta-analysis. GD compared with standard dosing resulted in a similar % time in therapeutic range (TTR) at ≤ 1 month follow-up (39.7% vs 40.2%; mean difference [MD], -0.52 [95% CI, -3.15 to 2.10]; P = .70) and higher % TTR (59.4% vs 53%; MD, 6.35 [95% CI, 1.76-10.95]; P = .007) at > 1 month follow-up, a trend toward lower risk of major bleeding (risk ratio, 0.46 [95% CI, 0.19-0.1.11]; P = .08) at ≤ 1 month follow-up and lower risks of major bleeding (0.34 [95% CI, 0.16-0.74], P = .006) at > 1-month follow-up, and shorter time to maintenance dose (TMD) (24.6 days vs 34.1 days; MD, -9.54 days [95% CI, -18.10 to -0.98]; P = .03) at follow-up but had no effects on international normalized ratio [INR] > 4.0, nonmajor bleeding, thrombotic outcomes, or overall mortality.

Conclusions: In the first month of genotype-guided warfarin therapy, compared with standard dosing, there were no improvements in % TTR, INR > 4.0, major or minor bleeding, thromboembolism, or all-cause mortality. There was a shorter TMD, and, after 1 month, improved % TTR and major bleeding incidence, making this a cost-effective strategy in patients requiring longer anticoagulation therapy.

PubMed Disclaimer

Figures

Figure 1 –
Figure 1 –
Flow diagram for study selection.
Figure 2 –
Figure 2 –
Forest plot for percentage time in therapeutic range. df = degrees of freedom; IV = inverse variance.
Figure 3 –
Figure 3 –
Forest plot for major bleeding. M-H = Mantel-Haenszel. See Figure 2 legend for expansion of other abbreviation.
Figure 4 –
Figure 4 –
Forest plot for time to maintenance dose by hazard ratio.
See this image and copyright information in PMC

References

    1. Kim MJ, Huang SM, Meyer UA, Rahman A, Lesko LJ. A regulatory science perspective on warfarin therapy: a pharmacogenetic opportunity. J Clin Pharmacol. 2009;49(2):138-146. - PubMed
    1. Garcia D, Regan S, Crowther M, Hughes RA, Hylek EM. Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population. Chest. 2005;127(6):2049-2056. - PubMed
    1. Lee A, Crowther M. Practical issues with vitamin K antagonists: elevated INRs, low time-in-therapeutic range, and warfarin failure. J Thromb Thrombolysis. 2011;31(3):249-258. - PubMed
    1. Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004;329(7456):15-19. - PMC - PubMed
    1. Wang D, Chen H, Momary KM, Cavallari LH, Johnson JA, Sadée W. Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement. Blood. 2008;112(4):1013-1021. - PMC - PubMed

Publication types