Abelacimab reduced major/clinically relevant non-major bleeding vs rivaroxaban in both OAC-naïve (HR 0.19; 95% CI 0.07-0.57) and OAC-experienced AF patients (HR 0.35; 95% CI 0.24-0.53).
RCT (n=1,279)
1:1:1
Does abelacimab reduce major/clinically relevant non-major bleeding compared to rivaroxaban in patients with atrial fibrillation, regardless of prior anticoagulation experience?
Abelacimab significantly reduces bleeding risk compared to rivaroxaban in patients with atrial fibrillation, with consistent relative benefits regardless of prior oral anticoagulation experience and potentially greater absolute safety benefit in OAC-naïve patients.
Abstract Background Prior tolerability of anticoagulation may be an indicator of bleeding risk, with implications for future bleeding events with ongoing anticoagulation. Abelacimab is a novel factor XI inhibitor that significantly reduced major/clinically relevant non-major (CRNM) bleeding relative to rivaroxaban in patients with atrial fibrillation (AF) in AZALEA-TIMI 71. Purpose We assessed whether prior anticoagulation experience modifies bleeding risk and the safety of abelacimab relative to rivaroxaban among patients enrolled in AZALEA-TIMI 71. Methods AZALEA-TIMI 71 randomized patients with AF 1:1:1 to one of two monthly abelacimab doses (150 or 90 mg) or to rivaroxaban. For this analysis, the abelacimab doses were pooled. Prior oral anticoagulation (OAC)-experienced patients were those treated with either a direct oral anticoagulant (DOAC) or a vitamin K antagonist (VKA) for ≥60 days prior to trial enrollment. Results Among 1,279 patients, 115 were OAC naïve (9%) and 1,164 (91%) were OAC-experienced (67% DOAC, 28% VKA, 5% both). In the rivaroxaban arm, the rate of major/CRNM bleeding was ~2-fold higher in OAC-naïve patients than in OAC-experienced patients (17.0 vs. 7.8 per 100 patient-years PY) (Figure A). In the abelacimab arms, the rates of major/CRNM bleeding were 3.8 and 2.8 per 100 PY in OAC-naïve and OAC-experienced patients, respectively. Abelacimab consistently reduced major/CRNM bleeding both in those without and with prior OAC experience (HR 0.19 0.07-0.57 and 0.35 0.24-0.53, respectively; p-int = 0.39), with pattern of greater absolute benefit in the OAC-naïve group (ARR 13.2 vs. 5.1 per 100 PY) (Figure A). Results in the OAC-experienced group were similar irrespective of the type of prior OAC experience (DOAC or VKA) (Figure B). Conclusion Prior OAC experience is an important indicator of bleeding risk among patients with AF. Compared with rivaroxaban, abelacimab consistently reduced the risk of bleeding irrespective of OAC experience, with potential for a greater absolute safety benefit among OAC-naïve patients.Figure A Figure B
Patel et al. (Sat,) conducted a rct in atrial fibrillation (AF) (n=1,279). Abelacimab vs. Rivaroxaban was evaluated on major/clinically relevant non-major (CRNM) bleeding. Abelacimab reduced major/clinically relevant non-major bleeding vs rivaroxaban in both OAC-naïve (HR 0.19; 95% CI 0.07-0.57) and OAC-experienced AF patients (HR 0.35; 95% CI 0.24-0.53).