Low dose vitamin K to improve INR control

Over coagulation with warfarin is associated with an increased risk of bleeding, while under coagulation with an increased risk of thrombosis. Maintaining patients on warfarin within their target INR range reduces this risk, and one way of monitoring  this is by calculating their % time in therapeutic range (%TTR). Ideally you would want this to be 100% – however that almost never happens for a variety of reasons such as poor compliance, drug interactions and dietary factors. Current NICE guidance on the use of warfarin in patients with atrial fibrillation suggest that poor control should be considered when TTR is <65%. In these (non-acute) cases NICE advocates asking the patient about:

  • The routine for taking warfarin, e.g. if they have missed any doses or taken too much.
  • Other medicines prescribed (e.g. antibiotics, oral steroids, miconazole oral gel), and purchased.
  • Use of alcohol, or drugs.
  • Use of herbal remedies.
  • Food and drink intake (e.g. green vegetables and cranberry juice).
  • General health — weight loss, acute illness (such as gastroenteritis), and smoking cessation can increase the effect of warfarin. Weight gain, diarrhoea, and vomiting can reduce the effect of warfarin.

If poor control can not be improved then NICE advocates “evaluating the risks and benefits of alternative stroke prevention strategies and discuss these with the person.”. One alternative might be to consider switching the patient to a novel oral anticoagulant such as apixaban or rivaroxaban. However potential barriers to implementing these drugs should also be considered. These include the reversibility of their effect as well as cost.

But what if another option was possible?

Warfarin works by blocking the effects of vitamin K, an important factor in ensuring that our blood is able to clot and we do not bleed excessively. Relatively little is stored in our body and much of it comes from our diet e.g. from green leafy vegetables (broccoli and spinach), certain cereals and vegetable oils. Patients with unstable control of anticoagulation have a consistently and significantly lower intake of vitamin K than their stable counterparts matched for age, sex, and indication for warfarinThere is also some evidence that adding a small dose of vitamin K to the warfarin improves this balance.

Last year we published a Cochrane systematic review entitled Vitamin K for improved anticoagulation control in patients receiving warfarin.

Screen Shot 2015-07-26 at 18.20.14The rationale was to look for randomised controlled trials that assessed the effect of a low dose of vitamin K, given as a supplement with warfarin, in improving INR control.

We only identified 2 studies with a total of 100 patients between them. Unfortunately one of the studies was available in abstract form only and we were unable to find more details of the study. The other study found that in the group of participants (n = 70) deemed to have poor INR control, the addition of 150 micrograms (mcg) of oral vitamin K significantly improved anticoagulation control in those with unexplained instability of response to warfarin.

We concluded that although there was some evidence to suggest a benefit, a larger, more definitive and high quality study was needed before this intervention could be considered for widespread use.

So what does this mean in practice?

Should we all be rushing to prescribe or advocate low dose vitamin K to patients on warfarin with poor INR control …well not just yet. Although if you do have patients with poor INR control it is certainly important to consider the possible factors that might affect their levels, including diet, as mentioned above.image

Anyway, if you want to read a very brief summary of our review as well as clinical implications, then we just did an editorial for the BMJ Heart journal “Cochrane corner” which you can read here.

Screen Shot 2015-07-26 at 18.36.37

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