Skip to main content

STUDY PROTOCOL article

Front. Neurol.
Sec. Stroke
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1468523
This article is part of the Research Topic Advances and controversies in ischemic stroke management: from prevention to diagnosis and acute treatment View all 87 articles

Optimal Antithrombotic Therapy in Ischemic Stroke Patients with Non-valvular Atrial Fibrillation and Atherothrombosis (ATIS-NVAF): Study Protocol for a Randomized Controlled Trial

Provisionally accepted
Shuhei Okazaki Shuhei Okazaki 1,2Haruko Yamamoto Haruko Yamamoto 3Koko Asakura Koko Asakura 3Katsuhiro Omae Katsuhiro Omae 3Hirotada Maeda Hirotada Maeda 3Kanta Tanaka Kanta Tanaka 3Shiro Yamamoto Shiro Yamamoto 1Teruyuki Hirano Teruyuki Hirano 4Yasuyuki Iguchi Yasuyuki Iguchi 5Manabu Sakaguchi Manabu Sakaguchi 6Masatoshi Koga Masatoshi Koga 3Masafumi Ihara Masafumi Ihara 3Kazunori Toyoda Kazunori Toyoda 3Teruo Noguchi Teruo Noguchi 3Nobuyuki Sakai Nobuyuki Sakai 7Hiroshi Yamagami Hiroshi Yamagami 1,8*
  • 1 Osaka National Hospital (NHO), Osaka, Japan
  • 2 Graduate School of Medicine, Osaka University, Suita, Ōsaka, Japan
  • 3 National Cerebral and Cardiovascular Center (Japan), Suita, Ôsaka, Japan
  • 4 School of Medicine, Kyorin University, Tokyo, Japan
  • 5 Jikei University School of Medicine, Minato, Tōkyō, Japan
  • 6 Osaka General Medical Center, Osaka, Japan
  • 7 Seijinkai Shimizu Hospital, Kyoto, Japan
  • 8 University of Tsukuba, Tsukuba, Ibaraki, Japan

The final, formatted version of the article will be published soon.

    The addition of antiplatelet therapy to anticoagulant therapy in patients with stroke with non-valvular atrial fibrillation (NVAF) and atherothrombotic disease may increase bleeding risk without reducing recurrent stroke risk. Aims: To evaluate the clinical benefits of anticoagulant monotherapy compared to combination therapy with anticoagulants and antiplatelet agents. Methods and design: This is an investigator-initiated prospective multicenter, randomized, openlabel, parallel-group clinical trial. Patients with NVAF and atherothrombotic disease who have had a recent ischemic stroke or transient ischemic attack will be eligible to participate in this trial. Study outcomes: The primary outcome is a composite of ischemic cardiovascular events, including cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization, and major bleeding events within 2 years after randomization. Sample size estimates: This study will enroll 400 patients, 200 receiving anticoagulant monotherapy and 200 receiving combination therapy. This sample size will provide 90% power (one-sided P=0.025) to detect a risk reduction in outcome events within 2 years, assuming event rates of 13% and 27% for each group, respectively, and a 10% loss to follow-up at a 2.5% significance level with one-sided log-rank tests at an interim analysis and a final analysis. Discussion: This will be the first study to assess the net clinical benefit of oral anticoagulant monotherapy in ischemic stroke patients with NVAF and atherothrombosis.

    Keywords: antiplatelet, Anticoagulant, Nonvalvular atrial fibrillation (NVAF), Atherothrombosis, ischemic stroke, randomized controlled trial

    Received: 22 Jul 2024; Accepted: 09 Oct 2024.

    Copyright: © 2024 Okazaki, Yamamoto, Asakura, Omae, Maeda, Tanaka, Yamamoto, Hirano, Iguchi, Sakaguchi, Koga, Ihara, Toyoda, Noguchi, Sakai and Yamagami. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hiroshi Yamagami, Osaka National Hospital (NHO), Osaka, Japan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.