Loading with warfarin, what’s the quickest and safest dose?

Key message: There is not enough evidence to show whether 10mg or 5mg loading dose of warfarin is safer or quicker. It may be more appropriate to use smaller doses in elderly patients.

Warfarin is a well established oral anticoagulant used all over the world for treatment and prevention of blood clots. One of the challenges of prescribing this drug is the variation in patient response to warfarin (some patients require two or three times larger doses than others for the same effect). The other challenge is the dose delay, usually of a few days, between taking warfarin and its blood thinning effect. This leads to delays in reaching its therapeutic threshold and can lead to unstable and elevated INR levels, raising the risk of bleeding complications.

A new review from the Cochrane Heart Group has now been published, comparing warfarin doses for patients beginning treatment.The review included 12 studies. Four studies compared 5mg and 10mg loading doses, four studies comparing genotype guided dosing, two comparing age adjusted doses to 10mg doses, one study compared 5mg and 2.5mg doses and one compared a calculated initiation dose to 5mg.

What did they find?

  • There was no significant difference between the 5mg and 10mg dose loading groups
  • When 2.5mg loading dose was compared to 5mg it was found to take longer to reach the target range
  • When an age adjusted dose was used in elderly patients compared to a 10mg loading dose, more patients reached a stable INR
  • Out of four studies looking at genotype guided strategy in one arm, three found no difference and the fourth which demonstrated that the genotype guided arm spent more time in-range had a control group with INRs significantly lower than expected

How good is the evidence?

There was a lack of high quality evidence. The overall risk of bias was found to be variable, most studies reported adequate randomisation methods but only two studies reported adequate allocation concealment data. Further high quality and adequately powered research needs to be carried out in this area, with adequate follow up and reporting of adverse events.

This review is helpful in showing that when starting warfarin for the first time there is not enough evidence to suggest whether 5mg or 10mg loading doses are safer or quicker. However in older patients smaller doses should be considered.

Links:

Mahtani  KR, Heneghan  CJ, Nunan  D, Bankhead  C, Keeling  D, Ward  AM, Harrison  SE, Roberts  NW, Hobbs  FDR, Perera  R. Optimal loading dose of warfarin for the initiation of oral anticoagulation. Cochrane Database of Systematic Reviews  2012, Issue 12. Art. No.: CD008685. DOI: 10.1002/14651858.CD008685.pub2.

Cochrane summary http://summaries.cochrane.org/CD008685/the-optimal-warfarin-dose-for-patients-beginning-therapy

Author:

Harry Boardman

Harry Boardman

Harry was with the UK Cochrane Centre from October 2012 – May 2013, where he undertook a fellowship in systematic reviews. He is currently part way through his Cardiology specialist training within the Oxford Deanery and before this undertook his medical training in London. He is interested evidence based medicine within cardiology, particular in relation to cardiovascular risk in women, imaging and devices.

You can follow Harry on Twitter @harry9bo

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Harry Boardman

About Harry Boardman

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Harry was with the UK Cochrane Centre from October 2012 – May 2013, where he undertook a fellowship in systematic reviews. He is now part way through a DPhil at the University of Oxford exploring pregnancy complications and future risk of heart disease in mothers. He is currently part way through his Cardiology specialist training within the Oxford Deanery and before this undertook his medical training in London. He is interested evidence based medicine within cardiology, particular in relation to cardiovascular risk in women, imaging and devices. You can follow Harry on Twitter @harry9bo

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