Vitamin K for improved anticoagulation control in patients receiving warfarin.
BACKGROUND
Effective use of warfarin involves keeping the international normalised ratio (INR) within a relatively narrow therapeutic range. However, patients respond widely to their dose of warfarin. Overcoagulation can lead to an increased risk of excessive bleeding, while undercoagulation can lead to increased clot formation. There is some evidence that patients with a variable response to warfarin may benefit from a concomitant low dose of vitamin K.


OBJECTIVE
To assess the effects of concomitant supplementation of low-dose oral vitamin K for anticoagulation control in patients being initiated on or taking a maintenance dose of warfarin.


METHODS
To identify previous reviews, we searched the Database of Abstracts of Reviews of Effects (DARE via The Cochrane Library, Wiley) (Issue 2, 2011). To identify primary studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL via The Cochrane Library, Wiley) (Issue 2, 2014), Ovid MEDLINE (R) In-Process & Other Non-Indexed Citations database and Ovid MEDLINE (R) (OvidSP) (1946 to 25 February 2014), Embase (OvidSP) (1974 to week 8 of 2014), Science Citation Index Expanded™ & Conference Proceedings Citation Index - Science (Web of Science™) (1945 to 27 February 2014), and the NHS Economics Evaluations Database (NHS EED) (via The Cochrane Library, Wiley) (Issue 2, 2014). We did not apply any language or date restrictions. We used additional methods to identify grey literature and ongoing studies.


METHODS
Randomised controlled trials comparing the addition of vitamin K versus placebo in patients initiating warfarin or already taking warfarin.


METHODS
Two review authors independently selected and extracted data from included studies. When disagreement arose, a third author helped reached a consensus. We also assessed risk of bias.


RESULTS
We identified two studies with a total of 100 participants for inclusion in the review. We found the overall risk of bias to be unclear in a number of domains. Neither study reported the time taken to the ﬁrst INR in range. Only one study (70 participants) reported the mean time in therapeutic range as a percentage. This study found that in the group of participants deemed to have poor INR control, the addition of 150 micrograms (mcg) oral vitamin K significantly improved anticoagulation control in those with unexplained instability of response to warfarin. The second study (30 participants) reported the effect of 175 mcg oral vitamin K versus placebo on participants with high variability in their INR levels. The study concluded that vitamin K supplementation did not significantly improve the stability of anticoagulation for participants on chronic anticoagulation therapy. However, the study was only available in abstract form, and communication with the lead author confirmed that there were no further publications. Therefore, we interpreted this conclusion with caution. Neither study reported any thromboembolic events, haemorrhage, or death from the addition of vitamin K supplementation.


CONCLUSIONS
Two included studies in this review compared whether the addition of a low dose (150 to 175 mcg) of vitamin K given to participants with a high-variability response to warfarin improved their INR control. One study demonstrated a significant improvement, while another smaller study (published in abstract only) suggested no overall benefit. Currently, there are insufficient data to suggest an overall benefit. Larger, higher quality trials are needed to examine if low-dose vitamin K improves INR control in those starting or already taking warfarin.
Nuffield Department of Primary Care Health Sciences, University of Oxford, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, Oxfordshire, UK, OX2 6GG.
Kamal R
KR
Mahtani
Carl J
CJ
Heneghan
David
D
Nunan
Nia W
NW
Roberts
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D006801:Humans; D019934:International Normalized Ratio; D016032:Randomized Controlled Trials as Topic; D014812:Vitamin K / Q000008:administration & dosage*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D014812:Vitamin K; D014859:Warfarin