Background:Early bleeding after percutaneous coronary intervention is associated with increased risk of death and myocardial infarction; however, the association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains unclear in patients with atrial fibrillation and stable coronary artery disease. We thus aimed to investigate this association.Methods:The AFIRE trial (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) was a multicenter, open-label trial conducted in Japan. This post hoc analysis included 2215 patients with atrial fibrillation and stable coronary artery disease treated with rivaroxaban or rivaroxaban plus an antiplatelet agent. MACCE was defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The association of bleeding with subsequent MACCE risk was investigated using time-adjusted Cox multivariate analysis after adjusting for baseline characteristics and time from bleeding. Bleeding events were classified according to the International Society on Thrombosis and Haemostasis criteria.Results:Among the 2215 patients, 386 (17.4%) had bleeding during follow-up, of whom 63 (16.3%) also experienced MACCE; MACCE incidence was higher in patients with bleeding than in those without (8.38% versus 4.20% per patient-year; hazard ratio, 2.01 [95% CI, 1.49–2.70]; P<0.001). The proportion of patients with both bleeding and MACCE (developed after bleeding) was 73.0% (46 of 63); 27.0% (17 of 63) experienced MACCE before bleeding. Time-adjusted Cox multivariate analysis revealed a temporal association between major bleeding and subsequent MACCE, with particularly high MACCE risks within 30 days after major bleeding (hazard ratio, 7.81 [95% CI, 4.20–14.54]).Conclusions:In patients with atrial fibrillation and stable coronary artery disease, major bleeding was strongly associated with subsequent MACCE. Thus, it is important to prevent major bleeding to avoid cardiovascular events and death.Registration:URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000016612. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419.Graphic Abstract:A graphic abstract is available for this article.

中文翻译：

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房颤伴稳定冠状动脉疾病的出血和随后的心血管事件和死亡：来自 AFIRE 试验的见解

背景：经皮冠状动脉介入治疗后的早期出血与死亡和心肌梗死风险增加有关；然而，在心房颤动和稳定型冠状动脉疾病患者中，出血与随后的主要不良心脑血管事件 (MACCE) 之间的关系仍不清楚。因此，我们旨在调查这种关联。方法：AFIRE 试验（利伐沙班治疗稳定型冠状动脉疾病患者的心房颤动和缺血事件）是在日本进行的一项多中心、开放标签试验。这项事后分析包括 2215 名接受利伐沙班或利伐沙班加抗血小板药物治疗的房颤和稳定性冠状动脉疾病患者。MACCE 被定义为中风、全身性栓塞、心肌梗死、需要血运重建的不稳定型心绞痛，或任何原因导致的死亡。在调整基线特征和出血时间后，使用时间调整的 Cox 多变量分析研究出血与随后的 MACCE 风险的关联。出血事件根据国际血栓与止血协会标准分类。结果：2215例患者中，386例（17.4%）随访期间出现出血，其中63例（16.3%）同时出现MACCE；有出血患者的 MACCE 发生率高于无出血患者（8.38% 对 4.20%/患者年；风险比，2.01 [95% CI，1.49–2.70]；在调整基线特征和出血时间后，使用时间调整的 Cox 多变量分析研究出血与随后的 MACCE 风险的关联。出血事件根据国际血栓与止血协会标准分类。结果：2215例患者中，386例（17.4%）随访期间出现出血，其中63例（16.3%）同时出现MACCE；有出血患者的 MACCE 发生率高于无出血患者（8.38% 对 4.20%/患者年；风险比，2.01 [95% CI，1.49–2.70]；在调整基线特征和出血时间后，使用时间调整的 Cox 多变量分析研究出血与随后的 MACCE 风险的关联。出血事件根据国际血栓与止血协会标准分类。结果：2215例患者中，386例（17.4%）随访期间出现出血，其中63例（16.3%）同时出现MACCE；有出血患者的 MACCE 发生率高于无出血患者（8.38% 对 4.20%/患者年；风险比，2.01 [95% CI，1.49–2.70]；磷<0.001)。出血和 MACCE（出血后发生）的患者比例为 73.0%（63 人中的 46 人）；27.0%（63 人中的 17 人）在出血前经历了 MACCE。时间调整的 Cox 多变量分析显示大出血和随后的 MACCE 之间存在时间关联，在大出血后 30 天内 MACCE 风险特别高（风险比，7.81 [95% CI，4.20-14.54]）。结论：在心房纤颤和稳定的冠状动脉疾病，大出血与随后的 MACCE 密切相关。因此，重要的是预防大出血以避免心血管事件和死亡。注册：URL：https://www.umin.ac.jp/ctr；唯一标识符：UMIN000016612。网址：https://www.clinicaltrials.gov；唯一标识符：NCT02642419。图形摘要：本文提供图形摘要。