Prior anticoagulation experience, bleeding risk, and safety of factor XI inhibition in atrial fibrillation: an analysis of AZALEA-TIMI 71

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.

We assessed whether prior anticoagulation experience modifies bleeding risk and the safety of abelacimab relative to rivaroxaban among patients enrolled in AZALEA-TIMI 71.

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.

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).

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 AFigure B