Key Points:
- Factor XI inhibitors have the potential to reduce thromboembolic events while minimizing major bleeding risks.
- Invasive procedures are frequent among patients with atrial fibrillation (AF), and the overall risk of major bleeding in this population is relatively low.
- In patients with AF mostly undergoing low risk invasive procedures, the rates of major bleeding or clinically relevant non-major bleeding were similar between those receiving abelacimab and those on rivaroxaban.
Every year, approximately 20% of patients with atrial fibrillation (AF) undergo invasive procedures, often necessitating temporary interruption of anticoagulation therapy to mitigate the risk of major bleeding. In the clotting cascade, activated factor XI appears essential for thrombosis but dispensable for hemostasis. Consequently, targeting Factor XI offers a promising approach to decouple hemostasis from thrombosis, potentially reducing the risk of major bleeding while still preventing thromboembolic events. The phase II AZALEA-TIMI 71 trial randomized 1,287 patients with AF at moderate to high stroke risk in a 1:1:1 fashion to receive either the long-acting monoclonal antibody abelacimab at a dose of 150 mg monthly, abelacimab at 90 mg monthly, both administered subcutaneously, or rivaroxaban at 20 mg daily. Both doses of abelacimab significantly reduced the primary endpoint of major or clinically relevant non-major bleeding (CRNM) by 67% compared to rivaroxaban. However, the efficacy of abelacimab in preventing periprocedural bleeding among patients with AF remained uncertain.
On September 2, 2024, Dr. Siddharth Patel from Brigham and Women’s Hospital in Boston, USA, presented the results of a sub-study of the AZALEA-TIMI 71 trial at ESC 2024 in London. This secondary analysis focused on examining periprocedural bleeding in AF patients undergoing invasive procedures. The primary endpoint was the occurrence of major or clinically relevant non-major bleeding (CRNM) within 30 days post-procedure. For low- or intermediate-risk procedures (as defined by the 2017 ACC Periprocedural Management Expert Pathway), continuation of abelacimab was encouraged. For high-risk elective procedures, interruption was advised, while for non-elective procedures, the use of an antifibrinolytic plus low-dose recombinant factor VIIa was recommended. For patients on rivaroxaban, standard care was followed, typically involving interruption 24-48 hours before an invasive procedure.
Approximately one-third of AF patients in the AZALEA-TIMI 71 trial underwent an invasive procedure. This sub-study included 1,280 patients (428 in rivaroxaban arm and 852 in the pooled abelacimab arm), with similar baseline characteristics. Most patients underwent low-risk procedures, and 1 in 4 of the procedures were non-elective. The median time from the last dose of abelacimab to the procedure was 29 days, most procedures occurred within the monthly dosing interval without interruption of the medication.
Of the 428 patients assigned to rivaroxaban, 36% underwent procedures and a similar proportion (34%) of those assigned to abelacimab both doses. The procedural bleeding risk was similar in both groups: for rivaroxaban, 5% for high bleeding risk, 19% for intermediate bleeding risk, and for abelacimab, 7% and 17% respectively. Approximately one out of five procedures were non-elective in both groups. There were 920 procedures among 441 patients, the most common was other (27%) that included different procedures followed by endoscopy/colonoscopy (19%), and coronary angiogram/ PCI ( 12%). The median time from last abelacimab dose to procedure was 29 ( 20-42) days, with half of the procedures occurring within 30 days.
Over a median follow-up of 2.1 years, the rates of major bleeding or CRNM bleeding were low and comparable between the two groups (14 events in total: 2.2% in the rivaroxaban group vs. 1.2% in the abelacimab group; RR 0.58, 95% CI 0.19-1.58), regardless of procedural risk or urgency. The use of anti-fibrinolytic therapy was 0.9% in the rivaroxaban group and 5.1% in the abelacimab group, blood transfusions were more common in the rivaroxaban group (5.3%) vs abelacimab (1.2%).
Discussing the study’s relevance, Dr. Patel stated, “Our data suggests that routine interruption of anticoagulation may not be necessary with Factor XI inhibition. However, further data for non-elective as well as for high bleeding risk procedures are necessary and would be further informative.”