Effect of prior antiplatelet therapy on large vessel occlusion in patients with non-valvular atrial fibrillation newly initiated on apixaban.

INTRODUCTION: We evaluated the effect of prior antiplatelet therapy on large vessel occlusion (LVO) in patients with non-valvular atrial fibrillation (NVAF) newly initiated on apixaban. METHODS: Patients with acute LVO with acute stroke due to NVAF or stenosis with NVAF started on apixaban within 14 days of onset were enrolled. We compared incidence of major bleeding, cerebral hemorrhage, ischemic events, cerebral infarction, and all-cause mortality between patients with and without prior antiplatelet therapy for acute LVO. We also compared these events between patients who continued antiplatelet therapy after onset (continued group) and those who discontinued it (discontinued group). Hazard ratios were estimated after adjusting for confounders; interaction was evaluated considering intravenous thrombolysis (IVT) or endovascular treatment (EVT) according to major bleeding. RESULTS: The study comprised 686 eligible patients (excluded [n = 194]; enrolled [n = 492]). The antiplatelet group consisted of older patients (mean: 79 vs. 76 years; p = 0.006) and had a higher cumulative incidence of major bleeding (7.3% vs. 2.9%, p = 0.003). The incidence of ischemic events and all-cause mortality was similar between the groups. Among the 109 patients in the antiplatelet group, the cumulative incidence of major bleeding, ischemic events, and all-cause mortality was comparable between continued group (n = 26) and discontinued group (n = 83). There were no significant differences between groups with and without IVT/EVT. However, major bleeding occured more frequently in the antiplatelet group without IVT. CONCLUSION: Prior antiplatelet therapy for LVO in patients with NVAF newly initiated on apixaban was associated with major bleeding, which was more frequent in the antiplatelet group without IVT.

Safety of Early Administration of Apixaban on Clinical Outcomes in Patients with Acute Large Vessel Occlusion.

Early administration of direct oral anticoagulants in patients with acute large vessel occlusion (LVO) and nonvalvular atrial fibrillation (NVAF) is a concern, as endovascular therapy (EVT) became highly utilized. We conducted a historical and prospective multicenter registry at 38 centers in Japan from July 2016 to February 2018. Patients aged ≥ 20 years with NVAF and acute LVO or stenosis who received apixaban within 14 days from onset were included. We compared patients who received apixaban < 48 h (Early group) and ≥ 48 h (Late group) after onset in terms of the primary outcome (a composite of ischemic events, major bleeding events, and all-cause deaths). The secondary outcomes were each component of the primary outcome. Among the 686 patients, the median time from onset to administration was 2.5 days (range, 0-14; Early 263, Late 423). The Alberta Stroke Program Early CT Score (ASPECTS) and diffusion-weighted imaging (DWI)-ASPECTS) were significantly higher in the Early group than in the Late group. Recombinant tissue plasminogen activator (rt-PA) and EVT were more utilized in the Early group (rt-PA 46% vs. 35%, p = 0.003; EVT 62% vs. 46%, p < 0.0001). The cumulative incidence of primary outcome was similar between groups (ischemic events: Early 1.9% vs. Late 0.5% at 30 days; 3.5% vs. 0.7% at 90 days, major bleeding 3.4% vs. 2.9% at 30 days; 5.0% vs. 3.4% at 90 days). Early administration of apixaban (< 48 h), after onset of acute LVO in patients with NVAF, was generally safe compared with those who received it Late (≥ 48 h). http://www.clinicaltrials.gov . Unique identifier: NCT02818868 (June 30, 2016).