Apixaban superior to warfarin for reducing brain bleed risk

The DOAC apixaban (Eliquis) is superior to warfarin for decreasing the risk of intracranial haemorrhage (ICH) in patients with atrial fibrillation, according to findings from a new study.

The new analysis, published in Blood, is the first to compare the DOAC to traditional warfarin in terms of the risk for ICH.

It showed that patients taking apixaban had significantly less ICH (0.33% per year) compared to those taking warfarin (0.80% per year) no matter the type and location of the bleed.

Director of the Haemophilia Centre at The Alfred Hospital in Melbourne, Associate Professor Huyen Tran said the findings confirm what most specialists have thought about the drug over the years but he added that despite this, many doctors still see warfarin as the safer option.

“What concerns me is that I still see – and not infrequently – a reluctance to take on these new agents because of the lack of an antidote and a perceived lack of safety … we’re not quite over that hump that will get us to use these agents to the rate that is clinically appropriate,” he told the limbic.

“I still see patients who have had it drummed into them somewhere along the line that the new drugs don’t have an antidote and so they should be taking warfarin – but if they’re on warfarin they’re two and a half times more likely to have an intracranial bleed,” he pointed out.

According to Professor Tran, in a few years’ time when DOAC antidotes become more freely available, people are not going to ‘blink an eye’ about using these agents over warfarin even though reversal agents will only need to be used rarely.

“At The Alfred, a major tertiary hospital, we see a lot of ICH bleeds and if you take the example of idarucizumab, the antidote for dabigatran, we’ve only used it four times since it became available 18 months ago so we’re not seeing a lot of bleeding with these agents. Having an antidote is an insurance policy but, like most insurance policies, you’re not going to use it very often.”

Meanwhile the vast majority of patients taking warfarin in the study showed INR values in the target range or below the target range within the two weeks prior to experiencing ICH, suggesting their warfarin dosage was properly or under-calibrated, respectively.

“To me, as a haematologist, that’s no surprise,” said Professor Tran noting that even patients with INR values within the therapeutic range will still be at greater risk of ICH compared to patients on a DOAC.

“People in the community have the perception that you only have a high risk of bleeding on warfarin if you’re INR is supratherapeutic – above 3 – but that’s absolutely not true. We need to remind people that if they’re on warfarin, even if they’re in the therapeutic range, they carry a higher risk of ICH.”

According to the study authors the highest risk for ICH was seen in patients who were aged 80 years or older or who had a previous stroke or mini-stroke.

Taking concomitant aspirin at the start of the study was also found to significantly increase the risk of ICH.

The finding highlights that doctors should remain vigilant about taking patients off aspirin when it’s no longer needed, warned Professor Tran.

“Because it’s readily available aspirin can be innocuous in the sense that a GP might put a patient on it with good intention, but the fact that a patient is taking it will often be forgotten about when they are put on a DOAC …people need to be mindful that as soon as you can cease aspirin, it should be stopped.”

The study used data from patients enrolled in the ARISTOTLE study who had ICH and who had received at least one dose of the study drug (n=18,140). They were tracked for a median of 1.8 years. ICH occurred in 174 patients and most of these events were spontaneous versus traumatic (71.2% vs. 28.8%), the study authors found.


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