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Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin.
Chest. 2015 Sep; 148(3):701-710.Chest

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.

Authors+Show Affiliations

Department of Medicine, LRGHealthcare, Laconia, NH. Electronic address: kdahal@lrgh.org.Department of Medicine, Englewood Hospital and Medical Center, Englewood, NJ.Section of Cardiology, Heart and Vascular Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Geisel School of Medicine, Dartmouth College, Hanover, NH.Calhoun Cardiology, University of Connecticut Health Center, Farmington, CT.Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Geisel School of Medicine, Dartmouth College, Hanover, NH; Department of Genetics, Dartmouth College, Hanover, NH; Institute of Quantitative Biomedical Science, Dartmouth College, Hanover, NH.Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA.Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Department of Genetics, Dartmouth College, Hanover, NH; Institute of Quantitative Biomedical Science, Dartmouth College, Hanover, NH.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25811981

Citation

Dahal, Khagendra, et al. "Meta-analysis of Randomized Controlled Trials of Genotype-Guided Vs Standard Dosing of Warfarin." Chest, vol. 148, no. 3, 2015, pp. 701-710.
Dahal K, Sharma SP, Fung E, et al. Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin. Chest. 2015;148(3):701-710.
Dahal, K., Sharma, S. P., Fung, E., Lee, J., Moore, J. H., Unterborn, J. N., & Williams, S. M. (2015). Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin. Chest, 148(3), 701-710. https://doi.org/10.1378/chest.14-2947
Dahal K, et al. Meta-analysis of Randomized Controlled Trials of Genotype-Guided Vs Standard Dosing of Warfarin. Chest. 2015;148(3):701-710. PubMed PMID: 25811981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin. AU - Dahal,Khagendra, AU - Sharma,Sharan P, AU - Fung,Erik, AU - Lee,Juyong, AU - Moore,Jason H, AU - Unterborn,John N, AU - Williams,Scott M, PY - 2015/3/27/entrez PY - 2015/3/27/pubmed PY - 2015/12/15/medline SP - 701 EP - 710 JF - Chest JO - Chest VL - 148 IS - 3 N2 - 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. SN - 1931-3543 UR - https://www.unboundmedicine.com/medline/citation/25811981/Meta_analysis_of_Randomized_Controlled_Trials_of_Genotype_Guided_vs_Standard_Dosing_of_Warfarin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-3692(15)50648-X DB - PRIME DP - Unbound Medicine ER -