Abelacimab reduces bleeding risk compared to rivaroxaban in atrial fibrillation

1. In this randomized controlled trial, abelacimab led to significantly lower rates of major or clinically relevant nonmajor bleeding compared to rivaroxaban in patients with atrial fibrillation at moderate-to-high stroke risk.

2. Abelacimab led to significantly reduced free factor XI levels compared to rivaroxaban. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: Atrial fibrillation has a high prevalence and considerably increases the risk of stroke five-fold. Accordingly, those with atrial fibrillation commonly take anticoagulation agents to prevent thromboembolic events. These include direct oral anticoagulants such as rivaroxaban. However, there are significant bleeding risks associated with these medications even though they are safer than previous therapies like warfarin. Accordingly, factor XI-targeted therapy is being explored as a method for reducing stroke risk in atrial fibrillation patients. This phase 2b, multinational RCT (AZALEA-TIMI 71) assessed the safety of abelacimab, a factor XI inhibitor, in anticoagulation therapy for atrial fibrillation. The study was halted early due to a substantial reduction in bleeding events in the abelacimab groups. While abelacimab demonstrated a significant decrease in bleeding compared to rivaroxaban, ischemic stroke incidence was slightly higher in the abelacimab groups, though not statistically significant. The study suggests abelacimab may be a safer alternative for patients at risk of anticoagulant-associated bleeding. Limitations include its open-label design for treatment assignment and the need for larger trials to confirm efficacy in stroke prevention.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: This multicenter, phase 2b, partially blinded RCT enrolled 1,287 patients with atrial fibrillation and a CHA2DS2-VASc score of ≥3. Patients were randomized in a 1:1:1 ratio to receive either subcutaneous abelacimab at 90 mg or 150 mg once monthly or oral rivaroxaban 20mg once daily (15 mg for patients with creatinine clearance ≤50 ml/min). The study aimed to assess safety outcomes, specifically major or clinically relevant nonmajor bleeding. At three months, the median reduction in free factor XI levels was 99% (interquartile range [IQR] 98–99) with 150 mg and 97% ([IQR] 51–99) with 90 mg of abelacimab. The trial was terminated early due to a significant reduction in major or clinically relevant nonmajor bleeding events in the abelacimab groups compared to rivaroxaban. The bleeding incidence rate was 3.2 events per 100 person-years for the 150 mg group and 2.6 events per 100 person-years for the 90 mg group, compared to 8.4 events per 100 person-years in the rivaroxaban group (Hazards Ratio [HR] 0.38; 95% Confidence Interval [CI], 0.24–0.60) for 150 mg vs. rivaroxaban, ([HR] 0.31; [CI], 0.19–0.51) for 90 mg vs. rivaroxaban, P<0.001 for both). Notably, gastrointestinal bleeding was markedly lower in the abelacimab groups (0.5% vs. 4.2% with rivaroxaban). However, the stroke incidence was slightly higher in the abelacimab groups (1.2% and 1.4% per year for 150 mg and 90 mg, respectively) than in the rivaroxaban group (0.8% per year), though the difference was not statistically significant. Overall, abelacimab demonstrated a strong safety profile with significantly lower bleeding risk than rivaroxaban, highlighting its potential as an alternative anticoagulant.

Image: PD

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