Abstract
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.
Objectives
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.
Search 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.
Selection criteria
Randomised controlled trials comparing the addition of vitamin K versus placebo in patients initiating warfarin or already taking warfarin.
Data collection and analysis
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.
Main 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.
Authors’ 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.
Plain language summary
The addition of vitamin K to improve anticoagulation stability for patients starting or already on warfarin
People with irregularity in heart activity, mechanical heart valves, and clotting disorders are at increased risk of developing blood clots, which could lead to stroke or death. Taking warfarin significantly reduces this risk. However, taking too much warfarin can lead to excessive bleeding, while taking too little reduces its benefit. To monitor this, patients taking warfarin must have regular blood tests to check if their dose of warfarin is stable enough to find the correct balance. There is some evidence that adding a small dose of vitamin K to the warfarin improves this balance. In this review, our primary outcomes were to assess if the addition of low-dose vitamin K to warfarin had an effect on the time taken to the first INR in range; the mean within the therapeutic range; or any adverse events, such as thromboembolic events, haemorrhage, or mortality. We found two studies that met our inclusion criteria. Neither study reported the time taken to the first INR in range. One study was only available in an abbreviated format, so we were unable to interpret the results fully. Nonetheless, it was suggested that the addition of vitamin K had no benefit. A second six-month study gave a small dose of vitamin K (150 mcg daily) or placebo to participants taking warfarin with existing poor INR control. This study reported the mean time in therapeutic range as a percentage and found that in the group of participants deemed to have poor INR control, the addition of 150 mcg oral vitamin K significantly improved their anticoagulation control. However, the study was relatively small. Neither study reported any adverse events, such as thromboembolism, haemorrhage, or death. We conclude that further larger, higher quality studies are needed to conclude whether adding vitamin K to warfarin for patients starting or already on warfarin improves their anticoagulation control.
