Last week’s FDA approval of a specific reversal agent for dabigatran and progress in specific antidotes to rivaroxaban and apixaban is reassuring for clinicians but it should not obscure the fact that these drugs are inherently safer than warfarin, says Professor Mark Crowther from McMaster University in Hamilton, Canada.
Idarucizumab, which reverses the direct thrombin inhibition of dabigatran, has also been approved recently by the European Medicines Agency.
Its efficacy was established in the RE-VERSE AD study (NEJM 2015; 373: 511-20), showing that a dose of 5 grams – a very large dose for a recombinant protein – completely reversed the anticoagulant effect of dabigatran within minutes in patients who had serious bleeding or required an urgent procedure.
“Development of reversal agents has been driven by perceptions of the epidemiology of NOAC-associated bleeding, but the reality is that warfarin is a more problematic drug,” Professor Crowther told delegates attending the Haematology Society of Australia and New Zealand conference held in Adelaide this week.
In randomised clinical studies warfarin was associated with major or fatal bleeding in 12-14% of patients, despite the availability of antidotes, while the rate for the NOACs ranged from 7-10%.
“The evidence suggests that bleeding is not more common with the newer anticoagulants, there is a lower risk of intracranial haemorrhage, and emergency surgery is associated with less bleeding than patients treated with warfarin,” he said.