title: Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin.
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: Department of Medicine, LRGHealthcare, Laconia, NH. Electronic address: kdahal@lrgh.org.
authors: Khagendra
authors: K
authors: Dahal
authors: Department of Medicine, Englewood Hospital and Medical Center, Englewood, NJ.
authors: Sharan P
authors: SP
authors: Sharma
authors: Section of Cardiology, Heart and Vascular Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Geisel School of Medicine, Dartmouth College, Hanover, NH.
authors: Erik
authors: E
authors: Fung
authors: Calhoun Cardiology, University of Connecticut Health Center, Farmington, CT.
authors: Juyong
authors: J
authors: Lee
authors: 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.
authors: Jason H
authors: JH
authors: Moore
authors: Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA.
authors: John N
authors: JN
authors: Unterborn
authors: 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.
authors: Scott M
authors: SM
authors: Williams
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D016032:Randomized Controlled Trials as Topic; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin