BACKGROUND The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. OBJECTIVE The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). METHODS AND ANALYSIS Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. CONCLUSIONS The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

中文翻译：

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左心耳封堵与新型口服抗凝剂预防房颤卒中的比较：多中心随机封堵-AF 试验的基本原理和设计。

背景 心房颤动 (AF) 的患病率在全球范围内不断增加，这是一个主要的临床和公共卫生问题，因为中风风险增加了 5 倍。使用新型口服抗凝剂 (NOAC) 进行口服抗凝是目前 AF 患者卒中预防的主要选择，尽管它会增加大出血的风险。既往有缺血性脑血管事件的患者发生复发性缺血事件和大出血的风险特别高。左心耳封堵术 (LAAO) 为高危患者的卒中预防提供了另一种选择，但目前证据有限。因此，需要将 LAAO 与 NOAC 进行比较的随机试验。目的 Occlusion-AF 试验旨在评估 LAAO 在降低卒中综合终点方面是否不劣于 NOAC 治疗，AF 和近期缺血性卒中或短暂性脑缺血发作 (TIA) 患者的全身性栓塞、大出血（出血学术研究联盟 ≥ 3）和全因死亡率。方法和分析 研究者发起的多中心、多国、随机开放标签非劣效性试验，采用盲法结果评估（PROBE 设计）。有记录的 AF 和 6 个月内发生缺血性中风或 TIA 的患者将有资格入组。主要排除标准是入组时改良 Rankin 量表 > 3、肾小球滤过率 < 15 ml/min 和预期寿命少于 2 年。总共 750 名患者将按 1:1 随机分配接受 NOAC 或 LAAO，使用 Amplatzer Amulet（Abbott，MN，USA）或 Watchman FLX（Boston Scientific，MN，USA），随后终身每天服用 75 mg 阿司匹林。随访将基于办公室和电话随访，并结合北欧各个国家的国家出院登记处的长期随访（10 年）。主要结果将是 2 年随访时中风、全身性栓塞、大出血 (BARC ≥ 3) 和全因死亡率的复合终点。结论 Occlusion-AF 试验旨在比较 LAAO 与 NOAC 治疗在血栓栓塞事件复发风险高的 AF 患者中的二级卒中预防，即既往有缺血性卒中或 TIA，以及其他适合抗凝治疗的患者。与这些患者的标准当代药物治疗相比，这些结果预计将显着有助于理解 LAAO 的影响。