January 22, 2025New England Journal of Medicine
Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation
Christian T. RuffSiddharth M. PatelRobert P. GiuglianoDavid A. MorrowBruce A. HugJulia KuderErica L. GoodrichShih-Ann ChenShaun G. GoodmanBoyoung JoungRóbert Gábor KissJindřich ŠpinarWojciech WojakowskiJeffrey I. WeitzSabina A. MurphyStephen D. WiviottSanobar ParkarDaniel M. BloomfieldMarc S. Sabatine
Key result
Abelacimab cuts major or clinically relevant bleeding by up to ~69% versus rivaroxaban in AFib.
- HR 0.38
- 95% CI 0.24 to 0.60
- P<0.001
- n=1,287
Why the study?
Does abelacimab reduce major or clinically relevant nonmajor bleeding compared to rivaroxaban in patients with atrial fibrillation at moderate-to-high risk of stroke?
Study Design
Type
RCT (n=1,287)
Blinding
Blinded (intervention) and open-label (control)
Randomization
1:1:1 ratio
Structured PICO
Does abelacimab reduce major or clinically relevant nonmajor bleeding compared to rivaroxaban in patients with atrial fibrillation at moderate-to-high risk of stroke?
P
Population
1,287 patients (median age 74, 44% women) with atrial fibrillation and a moderate-to-high risk of stroke.
I
Intervention
Abelacimab 150 mg or 90 mg subcutaneous injection once monthly administered in a blinded fashion
C
Comparator
Oral rivaroxaban 20 mg once daily administered in an open-label fashion
O
Outcome
Major or clinically relevant nonmajor bleedingsafety
Main Result
Hazard Ratio: 0.38 (95% CI 0.24–0.6)
Absolute Event Rate: 3.2% vs 8.4%
p-value: p=<0.001
Limitations
- Trial was stopped early
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This is the largest and longest trial comparing a factor XI inhibition with a DOAC. I think this data is conclusive that factor XI inhibition with abelacimab in this trial is far safer than any anticoagulant strategy we have to date, and that would be a tremendous advance for a patient's ability to be on and tolerate these medications.”
“I did not anticipate it would be this much safer. We would have been excited to see a 30% reduction in bleeding, but to see a 60% to 70% reduction in bleeding, almost eliminating gastrointestinal bleeding, that was greater than anticipated.”
“Gastrointestinal bleeding, which is by far the most common bleeding we see with DOAC therapy, was almost eliminated with both abelacimab doses.”
Implication
In patients with atrial fibrillation at moderate-to-high stroke risk, factor XI inhibition with abelacimab significantly reduced bleeding compared to rivaroxaban.
Abstract
BACKGROUND: Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown. METHODS: Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion. The primary end point was major or clinically relevant nonmajor bleeding. RESULTS: A total of 1287 patients underwent randomization; the median age was 74 years, and 44% were women. At 3 months, the median reduction in free factor XI levels with abelacimab at a dose of 150 mg was 99% (interquartile range, 98 to 99) and with abelacimab at a dose of 90 mg was 97% (interquartile range, 51 to 99). The trial was stopped early on the recommendation of the independent data monitoring committee because of a greater-than-anticipated reduction in bleeding events with abelacimab. The incidence rate of major or clinically relevant nonmajor bleeding was 3.2 events per 100 person-years with 150-mg abelacimab and 2.6 events per 100 person-years with 90-mg abelacimab, as compared with 8.4 events per 100 person-years with rivaroxaban (hazard ratio for 150-mg abelacimab vs. rivaroxaban, 0.38 [95% confidence interval {CI}, 0.24 to 0.60]; hazard ratio for 90-mg abelacimab vs. rivaroxaban, 0.31 [95% CI, 0.19 to 0.51]; P<0.001 for both comparisons). The incidence and severity of adverse events appeared to be similar in the three groups. CONCLUSIONS: Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban. (Funded by Anthos Therapeutics; AZALEA-TIMI 71 ClinicalTrials.gov number, NCT04755283.).
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Cite This Study
Ruff et al. (2025) conducted an RCT in Atrial Fibrillation (n=1,287). Abelacimab vs. Rivaroxaban 20 mg once daily was evaluated on Major or clinically relevant nonmajor bleeding (HR 0.38, 95% CI 0.24 to 0.60, p=<0.001). Abelacimab (150 mg and 90 mg) significantly reduced major or clinically relevant nonmajor bleeding compared to rivaroxaban (HR 0.38 [95% CI 0.24-0.60] and HR 0.31 [95% CI 0.19-0.51]; P<0.001 for both).