Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis

Author:

Khatib Rasha1,Ludwikowska Maja2,Witt Daniel M.3,Ansell Jack4,Clark Nathan P.5,Holbrook Anne6,Wiercioch Wojtek7,Schünemann Holger7,Nieuwlaat Robby7

Affiliation:

1. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL;

2. Evidence Prime Inc, Cracow, Poland;

3. Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT;

4. Hofstra Northwell School of Medicine, Hempstead, NY;

5. Clinical Pharmacy Anticoagulation and Anemia Service, Kaiser Permanente Colorado, Aurora, CO; and

6. Division of Clinical Pharmacology & Toxicology, Department of Medicine, and

7. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada

Abstract

Abstract Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation.

Publisher

American Society of Hematology

Subject

Hematology

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