From the Journals

Best anticoagulant for minimizing bleeding risk identified



A commonly prescribed direct oral anticoagulant (DOAC) has the lowest risk of bleeding, say researchers. Used to prevent strokes in those with atrial fibrillation (AFib), DOACs have recently become more common than warfarin, the previous standard treatment, as they do not require as much follow-up monitoring – which was “particularly valuable” during the COVID-19 pandemic – and have “less risk” of side effects, highlighted the authors of a new study, published in Annals of Internal Medicine.

However, the authors explained that, although current guidelines recommend using DOACs over warfarin in patients with AFib, “head-to-head trial data do not exist to guide the choice of DOAC.” So, they set out to try and fill this evidence gap by doing a large-scale comparison between all DOACs – apixaban, dabigatran, edoxaban, and rivaroxaban – in routine clinical practice.

Wallis Lau, PhD, University College London, and co–lead author, said: “Direct oral anticoagulants have been prescribed with increasing frequency worldwide in recent years, but evidence comparing them directly has been limited.”

One drug stood out

For the multinational population-based cohort study the researchers compared the efficacy and risk of side effects for the four most common DOACs. They reviewed data – from five standardized electronic health care databases that covered 221 million people in the United Kingdom, France, Germany, and the United States – of 527,226 patients who had been newly diagnosed with AFib between 2010 and 2019, and who had received a new DOAC prescription. The study included 281,320 apixaban users, 61,008 dabigatran users, 12,722 edoxaban users, and 172,176 rivaroxaban users.

Database-specific hazard ratios of ischemic stroke or systemic embolism, intracranial hemorrhage, gastrointestinal bleeding, and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model.

In total, 9,530 ischemic stroke or systemic embolism events, 841 intercranial hemorrhage events, 8,319 gastrointestinal bleeding events, and 1,476 deaths were identified over the study follow-up. The researchers found that all four drugs were comparable on outcomes for ischemic stroke, intercranial hemorrhage, and all-cause mortality.

However, they identified a difference in the risk of gastrointestinal bleeding, which they highlighted “is one of the most common and concerning side effects of DOACs.”

“Apixaban stood out as having lower risk of gastrointestinal bleeding,” said the authors, with a 19%-28% lower risk when compared directly with each of the other three DOACs. Specifically, apixaban use was associated with lower risk for gastrointestinal bleeding than use of dabigatran (HR, 0.81; 95% confidence interval, 0.70-0.94), edoxaban (HR, 0.77; 95% CI, 0.66-0.91), or rivaroxaban (HR, 0.72; 95% CI, 0.66-0.79).

The researchers also highlighted that their findings held true when looking at data only from those aged over 80, and those with chronic kidney disease, two groups that are “often underrepresented” in clinical trials.

Apixaban may be preferable

The researchers concluded that, among patients with AFib, apixaban use was associated with lower risk for gastrointestinal bleeding and similar rates of ischemic stroke or systemic embolism, intracranial hemorrhage and all-cause mortality, compared with dabigatran, edoxaban, and rivaroxaban.

“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 randomized controlled trials,” said Dr. Lau.

However, he emphasized that, “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.”

The authors all declared no conflicting interests.

A version of this article first appeared on Medscape UK.

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