UK researchers have identified the direct oral anticoagulant (DOAC) apixaban as having the lowest risk of gastrointestinal bleeding in a large observational study of atrial fibrillation (AF) patients.

Writing in the Annals of Internal Medicine, the researchers said that among patients with AF, apixaban was the DOAC with the lowest risk of gastrointestinal bleeding when compared with dabigatran, edoxaban, and rivaroxaban.

Unlike the vitamin K antagonist warfarin, DOACs can be administered in fixed doses without frequent coagulation monitoring, with research showing they are non-inferior to warfarin for stroke prevention and have lower risks for bleeding and osteoporotic bone fracture.

Current guidelines recommend DOACs over warfarin for patients with AF, and many countries advised patients to switch to DOACs during the Covid-19 pandemic to eliminate the need for frequent monitoring.

However, the researchers said there were no head-to-head clinical trial data available to help clinicians choose among the four available DOACs.

Using a standardised database network that covered 221 million patients in the UK, France, Germany and the US, researchers identified 526,226 people who were newly diagnosed with AF from 2010 and 2019 and who had received a new DOAC prescription.

The data included 281,320 apixaban users, 61,008 dabigatran users,12,722 edoxaban users, and 172,176 rivaroxaban users.

There were similar rates of ischemic stroke or systemic embolism, intracranial haemorrhage, and all-cause mortality between the four drugs in the study.

But apixaban was associated with a 19-28% lower risk of gastrointestinal bleeding when compared directly to each of the other three DOACs.

‘This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials,’ the authors wrote.

Co-lead author Dr Wallis Lau, of the UCL School of Pharmacy, said DOACs have been prescribed with increasing frequency worldwide recently, but evidence comparing them directly had been limited.

‘Our results indicate that apixaban may be preferable to other blood thinners because of the lower rate of gastrointestinal bleeding and similar rates of stroke, a finding that we hope will be supported by randomised controlled trials,’ Dr Lau said.

‘As with all medications, potential risks and benefits can differ between people, so considering the full spectrum of outcomes and side effects will still be necessary for each individual patient.’