medwireNews: In patients with atrial fibrillation (AF) and a moderate-to-high risk for stroke, treatment with the factor XI blocker abelacimab results in fewer bleeding events than the direct oral anticoagulant (DOAC) rivaroxaban, suggests the AZALEA–TIMI 71 study published in The New England Journal of Medicine.
After a median of 2.1 years, the incidence of major bleeding or clinically relevant nonmajor bleeding, as defined by International Society on Thrombosis and Haemostasis criteria, was a significant 62% and 69% lower among patients assigned to receive monthly abelacimab 150 mg or 90 mg, respectively, than among patients assigned to receive daily rivaroxaban 20 mg, say investigators Christian Ruff (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and colleagues.
In all, 18.3% of 430 patients receiving abelacimab 150 mg and 12.5% of 427 receiving abelacimab 90 mg experienced a bleeding event, compared with 26.2% of 430 patients receiving rivaroxaban. This equated to significantly lower incidence rates with abelacimab of 3.22 and 2.64 events per 100 person–years with the 150 mg and 90 mg doses, respectively, as compared with rivaroxaban, which had an incidence rate of 8.38 events per 100 person–years.
The significant reduction in bleeding events with abelacimab versus placebo led to a recommendation for early termination of the trial by the independent data monitoring committee, the researchers report.
In addition to fewer bleeding events, the team notes that “treatment with abelacimab resulted in markedly lower levels of free factor XI […] than treatment with rivaroxaban.” At 3 months, free factor XI levels had reduced by a median of 99% in the abelacimab 150 mg group and by a median of 97% in the 90 mg group. Ruff et al highlight that anticoagulants targeting factor XI “have the potential to be safer than currently available agents because there is mounting evidence that factor XI is essential for thrombosis but nonessential in most cases for hemostasis.”
The investigators also report a low incidence of major gastrointestinal bleeding with abelacimab, with two events in each abelacimab treatment group versus 18 events in the rivaroxaban group, a finding of interest, they say, as “the gastrointestinal tract is the most common site of bleeding with DOAC treatment.”
The study included 1287 adults aged 55 years and older with AF and a CHA2DS2-VASc score of at least 4 out of 9 points (median 5 points), with higher scores denoting a greater risk for stroke. The median age of the participants was 74 years, 56% were men, and 95% were White.
Although the trial was not designed to assess treatment efficacy due to the relatively small sample size, the incidence of stroke or systemic embolism was numerically more frequent in the abelacimab groups, with rates of 1.21 and 1.36 per 100 person–years with at the 150 mg and 90 mg doses, respectively, compared with 0.83 events per 100 person–years with rivaroxaban. The higher incidences were mostly driven by ischemic stroke, the researchers report.
They point out that the efficacy of abelacimab compared with placebo for preventing ischemic stroke and systemic embolization in high-risk patients with AF is currently under evaluation in the phase 3 LILAC–TIMI 76 trial.
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