Analysis Finds Less Bleeding — But Potentially Greater Mortality Risk — with Some Newer Anticoagulants

By Amy Orciari Herman

Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, DFASAM

Direct-acting oral anticoagulants — and apixaban in particular — generally confer lower risk for major bleeding than warfarin in patients with and without atrial fibrillation (AF), but there's a potentially increased mortality risk, according to an observational study in The BMJ.

Using two U.K. primary care databases, researchers studied nearly 200,000 adults who received first prescriptions for warfarin, dabigatran, rivaroxaban, or apixaban between 2011 and 2016. About half the patients had AF.

Among the findings, compared with warfarin:

• Apixaban was associated with a 34–40% lower risk for major bleeding in patients with and without AF.

• In patients with AF, both apixaban and dabigatran conferred reduced risk for intracranial bleeding.

• In patients without AF, rivaroxaban carried lower risk for intracranial bleeds and apixaban conferred lower risk for gastrointestinal bleeds.

• In patients with and without AF, lower-dose apixaban (<10 mg/day) was associated with a 27–34% increased risk for all-cause mortality, and rivaroxaban with a 19–50% increased risk.

Asked to comment, Dr. Harlan Krumholz of NEJM Journal Watch Cardiology said, "The authors find the results reassuring. I find them, at least in part, unsettling. There are many comparisons in the study and also the potential for unmeasured confounders — but the association of some newer anticoagulants with excess mortality is a red flag. We need to rapidly pool data sources and determine if this signal of harm is reproducible."