Research Summary · Cardiology

AZALEA–TIMI 71: Abelacimab Reduced Bleeding Risk (HR 0.38) vs Rivaroxaban in AF

August 11, 2026

Randomized patients

1,287

Median age

74 years

Women

44%

Primary endpoint rate (150 mg abelacimab)

3.2 events per 100 person-years

Primary endpoint rate (90 mg abelacimab)

2.6 events per 100 person-years

Primary endpoint rate (rivaroxaban 20 mg)

8.4 events per 100 person-years

Hazard ratio (150 mg vs rivaroxaban)

HR 0.38; 95% CI 0.24-0.60

Hazard ratio (90 mg vs rivaroxaban)

HR 0.31; 95% CI 0.19-0.51

Free factor XI reduction (150 mg at 3 months)

99% (interquartile range, 98 to 99)

Free factor XI reduction (90 mg at 3 months)

97% (interquartile range, 51 to 99)

Comparator

Rivaroxaban 20 mg once daily

ClinicalTrials.gov

NCT04755283

Clinical Perspective

Clinicians managing patients with atrial fibrillation and a moderate-to-high risk of stroke will be affected by these results. The AZALEA–TIMI 71 data support that monthly subcutaneous abelacimab produced markedly lower free factor XI levels and fewer major or clinically relevant nonmajor bleeding events than rivaroxaban, and clinicians should consult current prescribing information for full dosing guidance. Will abelacimab provide comparable long-term thromboembolic protection to rivaroxaban while maintaining lower bleeding rates?

Dr. Arjun Sharma · Cardiology

The AZALEA–TIMI 71 randomized trial, reported in the New England Journal of Medicine, compared monthly subcutaneous abelacimab with oral rivaroxaban in patients with atrial fibrillation at moderate-to-high risk of stroke and found fewer major or clinically relevant nonmajor bleeding events with abelacimab than with rivaroxaban (HR 0.38 for 150 mg and HR 0.31 for 90 mg) ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The trial was stopped early by the independent data monitoring committee because of a greater-than-anticipated reduction in bleeding events with abelacimab ^[1].

Clinical Context

Before AZALEA–TIMI 71, the safety of a factor XI inhibitor compared with a direct oral anticoagulant in atrial fibrillation had not been established; the trial was designed to address that gap by comparing abelacimab with rivaroxaban in patients with atrial fibrillation who were at moderate-to-high risk of stroke ^[1]. The enrolled population had features consistent with an older AF cohort (median age 74 years; 44% women) and was randomized to two monthly subcutaneous abelacimab doses or daily rivaroxaban 20 mg ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The study tested a coagulation-targeting strategy—direct inhibition of factor XI activation—measuring both pharmacodynamic effect (free factor XI levels) and clinical bleeding outcomes to assess whether factor XI pathway suppression could reduce bleeding relative to an established DOAC ^[1]. The trial’s early stop for benefit focuses attention on bleeding risk tradeoffs for emerging anticoagulant strategies and on the need for additional data on longer-term clinical outcomes ^[1].

Key Findings

The AZALEA–TIMI 71 trial showed abelacimab reduced the risk of major or clinically relevant nonmajor bleeding versus rivaroxaban (150-mg abelacimab: HR 0.38; 95% CI 0.24-0.60; 90-mg abelacimab: HR 0.31; 95% CI 0.19-0.51) ^[1].
Incidence rates of the primary end point were 3.2 events per 100 person-years with 150-mg abelacimab, 2.6 events per 100 person-years with 90-mg abelacimab, and 8.4 events per 100 person-years with rivaroxaban (20 mg once daily) ^[1].
Clinicians should consult current prescribing information for full dosing guidance.
At 3 months, median reductions in free factor XI levels were 99% (interquartile range, 98 to 99) with 150-mg abelacimab and 97% (interquartile range, 51 to 99) with 90-mg abelacimab, indicating marked pharmacodynamic suppression of factor XI activation with both doses ^[1].
The trial enrolled a total of 1,287 patients who underwent randomization; 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 ^[1].

Safety & Tolerability

The incidence and severity of adverse events appeared to be similar in the three groups ^[1].

Study Design

AZALEA–TIMI 71 was a randomized trial in which patients with atrial fibrillation and a moderate-to-high risk of stroke were assigned in a 1:1:1 ratio to receive subcutaneous abelacimab (150 mg once monthly or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion ^[1]. Clinicians should consult current prescribing information for full dosing guidance. A total of 1,287 patients underwent randomization; the median age was 74 years, and 44% were women ^[1]. The primary end point was major or clinically relevant nonmajor bleeding; key pharmacodynamic assessments included change in free factor XI levels at 3 months ^[1]. 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 ^[1]. Details on the trial phase designation, full statistical-analysis plan, and longer-term follow-up [Detail] was not available in the provided source excerpts. The trial is registered on ClinicalTrials.gov as NCT04755283 and was funded by Anthos Therapeutics ^[1].

FAQ

Q1 What did the AZALEA–TIMI 71 trial show?

The AZALEA–TIMI 71 trial randomized 1,287 patients with atrial fibrillation at moderate-to-high stroke risk to monthly subcutaneous abelacimab (150 mg or 90 mg) versus oral rivaroxaban 20 mg once daily and found fewer major or clinically relevant nonmajor bleeding events with abelacimab. Incidence rates were 3.2 events per 100 person-years (150 mg) and 2.6 events per 100 person-years (90 mg) versus 8.4 events per 100 person-years with rivaroxaban, with HRs of 0.38 (95% CI, 0.24 to 0.60) and 0.31 (95% CI, 0.19 to 0.51) respectively. The trial was stopped early by the independent data monitoring committee because of the observed reduction in bleeding events.

Q2 Who was enrolled in AZALEA–TIMI 71?

The trial enrolled 1,287 patients with atrial fibrillation judged to be at moderate-to-high risk of stroke. The median age of randomized patients was 74 years and 44% were women. Patients were randomized 1:1:1 to receive either monthly subcutaneous abelacimab at one of two doses or oral rivaroxaban 20 mg once daily, with abelacimab given in a blinded fashion and rivaroxaban administered open-label.

Q3 What were the side effects in AZALEA–TIMI 71?

The published report states that the incidence and severity of adverse events appeared to be similar across the three randomized groups. The source excerpts do not provide lists of specific adverse-event rates or types beyond that overall statement.

Q4 What does AZALEA–TIMI 71 mean for clinical practice?

The trial’s data indicate that monthly subcutaneous abelacimab produced marked suppression of free factor XI and was associated with fewer major or clinically relevant nonmajor bleeding events than rivaroxaban in this randomized population. These findings suggest a potential safety signal favoring lower bleeding with factor XI pathway inhibition, but the trial was stopped early and the report does not provide comprehensive long-term efficacy or detailed safety breakdowns; further evidence and full prescribing guidance are needed before changes to routine anticoagulant selection can be recommended.

References

PubMed — Primary trial publication (PMID 39842011)

AZALEA–TIMI 71: Abelacimab Reduced Bleeding Risk (HR 0.38) vs Rivaroxaban in AF

Direct Clinical Takeaway & Evidence Summary

AZALEA–TIMI 71: Abelacimab Reduced Bleeding Risk (HR 0.38) vs Rivaroxaban in AF

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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