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

Shinichi Yoshimura, Kazutaka Uchida, Nobuyuki Sakai, Hirotoshi Imamura, Hiroshi Yamagami, Kanta Tanaka, Masayuki Ezura, Tadashi Nonaka, Yasushi Matsumoto, Masunari Shibata, Hajime Ohta, Masafumi Morimoto, Norihito Fukawa, Taketo Hatano, Yukiko Enomoto, Masataka Takeuchi, Takahiro Ota, Fuminori Shimizu, Naoto Kimura, Yuki Kamiya, Norito Shimamura, Takeshi Morimoto, Shinichi Yoshimura, Kazutaka Uchida, Nobuyuki Sakai, Hirotoshi Imamura, Hiroshi Yamagami, Kanta Tanaka, Masayuki Ezura, Tadashi Nonaka, Yasushi Matsumoto, Masunari Shibata, Hajime Ohta, Masafumi Morimoto, Norihito Fukawa, Taketo Hatano, Yukiko Enomoto, Masataka Takeuchi, Takahiro Ota, Fuminori Shimizu, Naoto Kimura, Yuki Kamiya, Norito Shimamura, Takeshi Morimoto

Abstract

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).

Keywords: Acute large vessel occlusion; Apixaban; Bleeding; Stroke.

Conflict of interest statement

Dr. Yoshimura discloses research grants from Bristol-Myers Squibb and lecturer’s fees from Boehringer Ingelheim, Daiichi Sankyo, Bayer, Pfizer, and Bristol-Myers Squibb. Dr. Uchida reports lecturer’s fees from Daiichi Sankyo. Dr. Sakai reports a research grant from Daiichi Sankyo. Dr. Yamagami discloses research grants from Bristol-Myers Squibb; lecturer’s fees from Bayer, Daiichi Sankyo, Bristol-Myers Squibb, and Boehringer Ingelheim; and membership of the advisory boards for Daiichi Sankyo. Dr. Tanaka reports a lecturer’s fee from Daiichi Sankyo. Dr. Ezura reports lecturer’s fees from Boehringer Ingelheim and Pfizer. Dr. Shibata reports lecturer’s fees from Daiichi Sankyo. Dr. Takeuchi reports lecturer’s fees from Daiichi Sankyo. Dr. T Morimoto reports lecturer’s fees from Daiichi Sankyo and Pfizer, a manuscript fee from Pfizer, and membership of the advisory boards for Bristol-Myers Squibb. Dr. Kamiya discloses research grants from Bristol-Myers Squibb and lecturer’s fees from Daiichi Sankyo. Dr. Imamura, Dr. Nonaka, Dr. Matsumoto, Dr. Ohta, Dr. M Morimoto, Dr. Fukawa, Dr. Hatano, Dr. Enomoto, Dr. Ota, Dr. Shimizu, Dr. Kimura, and Dr. Shimamura have no disclosures to report.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Cumulative incidences of outcomes after apixaban administration. a Composite event of all-cause death, ISTH major bleeding events, and recurrent ischemic events. b All-cause death. c ISTH major bleeding events. d Ischemic events

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Source: PubMed

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