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Original Research: Antithrombotic Therapy |

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

Khagendra Dahal, MD; Sharan P. Sharma, MD; Erik Fung, MD, PhD; Juyong Lee, MD, PhD; Jason H. Moore, PhD; John N. Unterborn, MD; Scott M. Williams, PhD
Author and Funding Information

From the Department of Medicine (Dr Dahal), LRGHealthcare, Laconia, NH; the Department of Medicine (Dr Sharma), Englewood Hospital and Medical Center, Englewood, NJ; the Section of Cardiology, Heart and Vascular Center (Dr Fung), and the Norris Cotton Cancer Center (Drs Moore and Williams), Dartmouth-Hitchcock Medical Center, Lebanon, NH; the Geisel School of Medicine (Drs Fung and Moore), the Department of Genetics (Drs Moore and Williams), and the Institute of Quantitative Biomedical Science (Drs Moore and Williams), Dartmouth College, Hanover, NH; the Calhoun Cardiology Center (Dr Lee), University of Connecticut Health Center, Farmington, CT; and the Department of Medicine (Dr Unterborn), St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA.

CORRESPONDENCE TO: Khagendra Dahal, MD, Department of Internal Medicine, LRGHealthcare, 80 Highland St, Laconia, NH 03246; e-mail: kdahal@lrgh.org


FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(3):701-710. doi:10.1378/chest.14-2947
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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.

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