经皮冠状动脉介入治疗 1 年后合并心房颤动和稳定型冠状动脉疾病患者双联抗血小板治疗与单抗血小板治疗的开放性随机临床试验比较
Open-Label Randomized Trial Comparing Oral Anticoagulation With and Without Single Antiplatelet Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease Beyond 1 Year After Coronary Stent Implantation.
机构信息
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan (Y.M.-N., S.S., A.K., H.S., T.K.).
Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan (T.M.).
出版信息
Circulation. 2019 Jan 29;139(5):604-616. doi: 10.1161/CIRCULATIONAHA.118.036768.
BACKGROUND
Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting.
METHODS
This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months.
RESULTS
Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79-1.72; P=0.20 for noninferiority, P=0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71-1.39; P=0.016 for noninferiority, P=0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively.
CONCLUSIONS
This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.
背景
尽管指南和共识文件中有相关建议，但对于在冠状动脉支架置入术后 1 年以上且患有心房颤动和稳定型冠状动脉疾病的患者，尚无单独使用口服抗凝剂（OAC）而不联合抗血小板治疗（APT）的随机对照试验。
方法
这是一项前瞻性、多中心、开放标签、非劣效性试验，以 1:1 的比例随机比较 OAC 单独治疗与 OAC 联合单 APT 治疗在支架置入术后 1 年以上的心房颤动患者。主要终点是全因死亡、心肌梗死、卒中和全身性栓塞的复合终点。主要次要终点是根据国际血栓与止血协会分类的主要终点或主要出血的复合终点。尽管该试验设计在 12 个月内招募 2000 名患者，但在 38 个月内招募了 696 名患者后提前终止。
结果
平均年龄为 75.0±7.6 岁，85.2%的患者为男性。OAC 组中 75.2%的患者使用华法林，24.8%的患者使用直接口服抗凝剂。平均 CHADS 评分为 2.5±1.2。中位随访 2.5 年期间，OAC 单药组 54 例（15.7%）和 OAC 联合 APT 组 47 例（13.6%）发生主要终点事件（风险比，1.16；95%CI，0.79-1.72；非劣效性 P=0.20，优效性 P=0.45）。OAC 单药组 67 例（19.5%）和 OAC 联合 APT 组 67 例（19.4%）发生主要次要终点事件（风险比，0.99；95%CI，0.71-1.39；非劣效性 P=0.016，优效性 P=0.96）。心肌梗死分别发生在 8 例（2.3%）和 4 例（1.2%）患者，而卒中或全身性栓塞分别发生在 13 例（3.8%）和 19 例（5.5%）患者。大出血分别发生在 27 例（7.8%）和 36 例（10.4%）患者。
结论
这项随机试验未证实在冠状动脉支架置入术后 1 年以上且患有心房颤动和稳定型冠状动脉疾病的患者中，OAC 单独治疗不劣于 OAC 联合 APT。由于患者入组提前终止，因此该研究的效能不足，结果不确定。需要进一步开展更大规模的研究以确定该人群的最佳抗血栓治疗方案。
临床试验注册
网址：https://www.clinicaltrials.gov。独特标识符：NCT01962545。
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