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.