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Randomized Controlled Trial
. 2025 Jun 17;85(23):2288-2298.
doi: 10.1016/j.jacc.2025.04.018.

Long-Acting Factor XI Inhibition and Periprocedural Bleeding: An Analysis From AZALEA-TIMI 71

Siddharth M Patel  1 , Robert P Giugliano  2 , David A Morrow  2 , Sanobar Parkar  3 , Hannah Shapiro  2 , Bruce Hug  3 , Julia F Kuder  2 , Erica L Goodrich  2 , Shih-Ann Chen  4 , Shaun G Goodman  5 , Boyoung Joung  6 , Robert G Kiss  7 , Wojciech Wojakowski  8 , Jeffrey I Weitz  9 , Sabina A Murphy  2 , Stephen D Wiviott  2 , Daniel Bloomfield  3 , Marc S Sabatine  2 , Christian T Ruff  2
Affiliations
Randomized Controlled Trial

Long-Acting Factor XI Inhibition and Periprocedural Bleeding: An Analysis From AZALEA-TIMI 71

Siddharth M Patel et al. J Am Coll Cardiol. .

Abstract

Background: In AZALEA-TIMI 71 (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-Thrombolysis In Myocardial Infarction 71), abelacimab, a novel factor XI inhibitor, significantly reduced the rate of major or clinically relevant nonmajor (CRNM) bleeding compared with rivaroxaban in patients with atrial fibrillation (AF). Abelacimab is long-acting with a half-life of ∼28 days.

Objectives: The purpose of this study was to examine periprocedural bleeding among patients undergoing invasive procedures in the context of long-acting factor XI inhibition with abelacimab.

Methods: AZALEA-TIMI 71 was designed to assess the bleeding profile of abelacimab relative to rivaroxaban. Patients were randomized to either 1 of 2 abelacimab doses (90 or 150 mg subcutaneously monthly) or to rivaroxaban daily. Invasive procedures occurring during follow-up were categorized as low, intermediate, or high bleeding risk. Periprocedural bleeding events were identified as major/CRNM bleeds, as adjudicated by a clinical events committee blinded to treatment assignment, occurring within 30 days after a procedure, and related to the procedure on blinded review.

Results: A total of 920 procedures occurred in 441 patients, with approximately 1 in 3 patients in both rivaroxaban and abelacimab arms undergoing an invasive procedure over a median follow-up of 2.1 years. Most procedures were low bleeding risk (n = 696, 75.7%) and elective (n = 686, 74.6%). The median time to a procedure from the last dose of abelacimab was 29 days (Q1-Q3: 20-42 days), with 336 of the 602 (55.8%) procedures in the abelacimab arms occurring within the monthly dosing interval. Overall, the occurrence of periprocedural major or CRNM bleeding was low (<2% of all procedures), representing 1.2% of all procedures in the abelacimab arms vs 2.2% of all procedures in the rivaroxaban arm (RR [risk ratio]: 0.54; 95% CI: 0.19-1.58), with consistent results in the individual abelacimab dosing arms. For procedures occurring within 30 days of an abelacimab dose, major or CRNM bleeds occurred in only 3 of the 336 (0.9%) procedures.

Conclusions: These data illustrate that patients with AF treated with abelacimab, a long-acting factor XI inhibitor, can undergo invasive procedures with low rates of bleeding. Moreover, these findings suggest that routine interruption of anticoagulation may not be necessary for all procedures in the context of factor XI inhibition, particularly for procedures that have low bleeding risk.

Keywords: antithrombotic therapy; atrial fibrillation; factor XI; oral anticoagulant.

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Conflict of interest statement

Funding Support and Author Disclosures AZALEA-TIMI 71 was funded by Anthos. Dr Patel is supported by a K12TR004381 award through Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health); and has received consultant/advisory fees from Janssen. Drs Patel, Giugliano, Morrow, Kuder, Goodrich, Murphy, Wiviott, Sabatine, and Ruff are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Inc, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Ionis Pharmaceuticals, Inc, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Roche, Saghmos Therapeutics, Inc, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, Verve Therapeutics, Inc, and Zora Biosciences. Dr Giugliano has received clinical trials/research support from Anthos Therapeutics and Daiichi-Sankyo; has received honoraria for lectures/CME programs from Big Sky Cardiology, Daiichi-Sankyo, Medical Education Resources, Menarini, SAJA, Shanghai Medical, and SUMMEET; and serves as a consultant for Artivion, AstraZeneca, Celecor, Daiichi-Sankyo, Perosphere, Samsung, Sanofi, and SFJ Pharmaceuticals. Drs Parkar, Hug, and Bloomfield are employed by Anthos. Dr Morrow has received consulting fees from Abbott Laboratories, ARCA Biopharma, InCarda, Inflammatix, Merck and Co, Novartis, and Roche Diagnostics. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Alnylam, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd, Daiichi Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Roche, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support/honoraria from the Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, Jewish General Hospital, CIUSSS Centre-Ouest-de-l'Ile-de-Montreal, New York University Clinical Coordinating Centre, PERFUSE Research Institute, Peter Munk Cardiac Centre Clinical Trials and Translation Unit, Ted Rogers Centre for Heart Research, and TIMI Study Group (Brigham Health). Dr Joung has received research grant support from Abbott, Boston Scientific, Huino, and Samjin. Dr Kiss has received speaker fees from Bayer, AstraZeneca, Novo Nordisk, Pfizer, Boehringer Ingelheim, and Merck. Dr Weitz has received consultancy and advisory fees from Alnylam, Anthos, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Ionis, J and J, Merck, Pfizer, Regeneron, and Servier. Dr Wiviott has received research grants from Amgen, AstraZeneca, Janssen, Merck, and Pfizer; has received consulting fees or honoraria from Icon Clinical, Novo Nordisk, Varian, and Harvard Medical School; and his spouse is an employee of Pfizer and a former employee of Vertex, Flagship Pioneering, and Merck. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Ionis, Marea, Merck, Novartis, Pfizer, Saghmos Therapeutics, and Verve Therapeutics; has consulted for Amgen, AMPEL BioSolutions, Anthos Therapeutics, Inc, AstraZeneca, Beren Therapeutics, Boehringer Ingelheim, Dr Reddy’s Laboratories, Fibrogen, Merck, Moderna, Novo Nordisk, Precision BioSciences, Silence Therapeutics; and is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from Abiomed, Inc, ARCA Biopharma, Inc, Janssen Research and Development, LLC, MedImmune, Regeneron Pharmaceuticals, Inc, Roche, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, and Zora Biosciences. Dr Ruff has received research grants through his institution from Anthos, AstraZeneca, Daiichi Sankyo, Janssen, and Novartis; and has received honoraria for scientific advisory boards and consulting from Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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