A Multicenter, RandomiZed, Active-ControLled Study to Evaluate the Safety and Tolerability of Two Blinded Doses of Abelacimab Compared With Open-Label Rivaroxaban in Patients With Atrial Fibrillation - AZALEA-TIMI 71

Contribution To Literature:

The AZALEA-TIMI 71 trial showed that both doses of abelacimab (90 mg and 150 mg monthly) were superior to rivaroxaban 20 mg daily in reducing bleeding events among patients with AF and a high CHA2DS2-VASc score.


The goal of this phase 2 trial was to compare the safety and efficacy of 2 doses of abelacimab compared with rivaroxaban among patients with atrial fibrillation (AF) and a moderate–high risk of stroke.

Study Design

Eligible patients were randomized in a 1:1:1 fashion to either abelacimab 150 mg (n = 427), abelacimab 90 mg (n = 425), or rivaroxaban 20 mg (n = 430). Abelacimab was administered as a subcutaneous monthly injection, while rivaroxaban was administered daily in oral form.

  • Total number of enrollees: 1,287
  • Duration of follow-up: 1.8 years
  • Mean patient age: 74 years
  • Percentage female: 44%

Inclusion criteria:

  • Age ≥55 years
  • Patients with a history of AF or atrial flutter with planned indefinite anticoagulation
  • Patients with a CHA2DS2-VASc score of ≥4 OR a CHA2DS2-VASc score of ≥3 with ≥1 of the following:
    • Planned concomitant use of antiplatelet medication (i.e., aspirin and/or P2Y12 inhibitor) for the duration of the trial
    • Creatinine clearance (CrCl) ≤50 mL/min by the Cockcroft-Gault equation

Exclusion criteria:

  • History of hypersensitivity to any of the study drugs (including rivaroxaban) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for rivaroxaban
  • Patients with an intracranial or intraocular bleed within the 3 months prior to screening
  • Clinically significant mitral stenosis (valve area <1.5 cm2)
  • Mechanical heart valve or other indication for anticoagulation therapy other than AF (e.g., venous thromboembolism [VTE])
  • Known presence of an atrial myxoma or left ventricular thrombus
  • History of left atrial appendage closure or removal
  • Active endocarditis

Other salient features/characteristics:

  • Median CHA2DS2-VASc score: 5
  • Prior ischemic stroke: 15%, prior bleed: 7%
  • Planned concomitant antiplatelet use: 26%

Principal Findings:

The trial terminated early due to greater than expected benefit with abelacimab. The primary endpoint, major or non–clinically relevant major bleeding, for abelacimab 150 mg vs. abelacimab 90 mg vs. placebo, was: 2.7% vs. 1.9% vs. 8.1% (p < 0.001 for both doses of abelacimab vs. placebo).

  • Hazard ratio (HR) for abelacimab 150 mg vs. placebo: 0.33 (95% confidence interval [CI] 0.19–0.55, p < 0.001)
  • HR for abelacimab 90 mg vs. placebo: 0.23 (95% CI 0.13–0.42, p < 0.001)
  • Major bleeding: 1.0% vs. 0.7% vs. 3.7% (p < 0.05)
  • Gastrointestinal bleeding: 0.1% vs. 0.1% vs. 2.1%
  • Intracerebral hemorrhage: 0.3% vs. 0.6% vs. 0.6%

Secondary outcomes for abelacimab 150 mg vs. abelacimab 90 mg vs. rivaroxaban:

  • Stroke or systemic embolism: 1.1% vs. 1.4% vs. 1.0% (p = 0.81; p = 0.45)
  • Ischemic stroke: 1.1% vs. 1.3% vs. 0.7%
  • All-cause mortality: 2.4% vs. 2.8% vs. 3.1%


The results of this phase II trial indicate that both the tested doses of abelacimab (90 mg and 150 mg monthly) are superior to rivaroxaban 20 mg daily in reducing bleeding events among patients with AF and a high CHA2DS2-VASc score. Abelacimab is administered as a once-monthly subcutaneous injection. It is a highly selective fully human monoclonal antibody to factor XI. It binds to FXI and prevents formation of activated FXI, which is an essential component of the intrinsic clotting pathway. In theory, this could suppress pathologic thrombosis but preserve physiological hemostasis.

In another phase II trial, the 75 mg and 150 mg doses of abelacimab were shown to be superior to enoxaparin in preventing VTE post–total knee replacement. These are promising findings. A phase III trial (LILAC-TIMI 76) is assessing the safety and efficacy of abelacimab 150 mg compared with placebo among patients with AF deemed unsuitable for anticoagulation.


Presented by Dr. Christian Ruff at the American Heart Association Scientific Sessions, Philadelphia, PA, November 12, 2023.

Clinical Topics: Arrhythmias and Clinical EP, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: AHA23, Anticoagulation Management, Atrial Fibrillation

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