title: Anticoagulation control with daily low-dose vitamin k to reduce clinically adverse outcomes and international normalized ratio variability: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Difficulties managing warfarin therapy have led to speculation that daily supplementation with a low dose of vitamin K might improve anticoagulation control and clinical outcomes. Thus we sought to review the available medical literature systematically examining the effectiveness of low-dose vitamin K supplementation for the reduction of clinically relevant adverse events due to vitamin K antagonist (VKA) use and for stabilization of the international normalized ratio (INR).
  
  
  METHODS
  We searched the Medline and Embase databases, the Cochrane Library, International Pharmaceutical Abstracts, and the U.S. National Institutes of Health clinical trials registry for randomized controlled trials of vitamin K supplementation versus placebo in patients receiving a VKA. We evaluated the outcomes of hemorrhage, thromboembolic events, and percentage of time in therapeutic range (TTR) of INRs by using the Grading of Recommendations Assessment, Development and Evaluation system for rating quality of evidence in the abstracted studies.
  
  
  METHODS
  All randomized controlled trials studies published between 1970 and August 2012 which fitted our search strategy.
  
  
  METHODS
  Patients over the age of 18 years on VKA therapy.
  
  
  RESULTS
  Of the 624 studies we identified and screened, three studies (626 patients) were included in the meta-analysis. Most of the patients had a satisfactory TTR at baseline. We found low-quality evidence--downgraded for imprecision and risk of bias (i.e., limitation in study design and/or execution)--of no effect of vitamin K use (100 to 200 μg) on hemorrhagic events (relative risk [RR] 3.2, 95% confidence interval [CI] 0.2-64.2) and thromboembolic events (RR 2.2, 95% CI 0.1-47.5) and a significant but clinically unimportant effect on TTR with an absolute increase of 3.5% (95% CI 1.1-6.0).
  
  
  CONCLUSIONS
  This meta-analysis, despite the few studies and overall low quality, suggests no beneficial role of low-dose (100 to 200 μg) vitamin K supplementation on the reduction of clinically relevant adverse events in patients taking VKAs, despite a small improvement of the TTR. Data were insufficient, however, from patients with unstable INRs.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Lam
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Witt
authors.forename: Per Olav
authors.initials: PO
authors.lastname: Vandvik
authors.forename: Fareeha
authors.initials: F
authors.lastname: Qayyum
authors.forename: Anne M
authors.initials: AM
authors.lastname: Holbrook
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods* / Q000592:standards; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D016896:Treatment Outcome; D014812:Vitamin K / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: INR variability; bleeding; systematic review; vitamin K; vitamin K antagonist