Australian cardiologists pour cold water on latest DOAC safety data

Fresh concerns have been raised about an increased risk of acute MI in patients who are taking dabigatran or rivaroxaban for atrial fibrillation, claim researchers involved in a large retrospective study that has revisited the issue.

However, speaking to the limbic cardiologists say the findings most likely reflect the confounding nature of ‘real-world’ studies.

Current use of either of the DOACs by patients was associated with about twice the risk of acute MI than that seen among patients taking warfarin, the researchers from the Netherlands reported in their paper published in Pharmacoepidemiology.

In addition, after accounting for potential confounders, current use of aspirin as monotherapy had a similar higher risk of acute MI compared with warfarin-treated patients while past use of aspirin was also associated with an elevated risk.

It’s likely that “VKAs probably have greater beneficial effects on AMI than DOACs” the authors say, arguing that more research is warranted because of increasing use of the newer agents.

But commenting on the study, Associate Professor John Amerena, director of the Geelong Cardiology Research Unit in Victoria told the limbic that it was hard to draw any meaningful conclusions from the study when the sample size for each treatment group were so disparate.

The analysis included 30,146 patients who were diagnosed with AF and initiated on warfarin (43.4%), low-dose aspirin (51.1%), rivaroxaban or dabigatran (4.2%), or a combination of those drugs (1.3%) between 2008 and 2014. Among the DOAC users, 71.6% were given rivaroxaban and the rest dabigatran.

“There were 1200 patients on a DOAC compared to nearly 13,000 on warfarin so, comparing the groups on those numbers where so few patients were on a DOAC – less than 10% of the total number of patients on warfarin – is really a stretch.”

Whether DOACs increase MI risk has been debated ever since the RE-LY trial showed that the rate of MI was higher in patients taking dabigatran than in those treated with warfarin, the investigators pointed out.

However, Professor Amerena questioned their motivation for citing that data adding that subsequent randomised and observational studies had refuted those claims.

In 2014 the FDA, who also weighed in on the issue as part of a safety review of dabigatran, announced that a large database study failed to show an excess risk of MI with the drug, Professor Amerena also noted.

“The FDA have since said there is no signal of increased MI in the RE-LY study – that data is published and is freely available. What raises my suspicions is when the authors [of the current study] have chosen to ignore data that’s been published – that’s a bit of a concern,” he said.

Meanwhile, interventional cardiologist and head of the coronary care and coronary interventions at Concord Hospital in Sydney, Professor David Brieger, who also spoke to the limbic, said the evidence base surrounding the issues is conflicting.

“We are now swamped with real world studies; it is clear that confounding is a real issue which explains why they often now conflict with each other.  I have reached the point where I disregard them, particularly if they conflict with the randomised trial information.”

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