Aims The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. Methods and results Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh–Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8–20.9] and 19.7 in CON (95% CI 17.5–22.2), difference −1.5 (95% CI −5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. Conclusions In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. Clinical trial registration ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522.

中文翻译：

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ISCHEMIA 试验中初始侵入性与初始保守性治疗策略对复发和总心血管事件的影响

目的 医学和侵入性方法比较健康有效性的国际研究 (ISCHEMIA) 试验预先指定了一项分析，以确定除了首次事件之外是否考虑复发性心血管事件会改变对治疗效果的理解。方法和结果 稳定性冠状动脉疾病 (CAD) 和负荷测试中度或重度缺血的患者随机接受初始侵入性 (INV) 或初始保守性 (CON) 治疗。主要结局是心血管死亡、心肌梗死 (MI) 和因不稳定型心绞痛、心力衰竭或心脏骤停住院的复合结局。Ghosh-Lin 方法用于估计以死亡为竞争风险的总事件的平均累积发生率。5179 名 ISCHEMIA 患者经历了 670 次指标事件（318 次 INV，352 CON）和 203 例复发事件（102 INV，101 CON）。在 9.8% 的 INV 和 10.8% 的 CON 患者中观察到单一主要事件，而在 2.5% 和 2.8% 中分别观察到≥2 次主要事件。复发事件的患者年龄较大；有更频繁的高血压、糖尿病、既往心梗或脑血管疾病；并且有更多的多血管 CAD。4 年内每 100 名患者的主要终点事件平均数为 INV 中的 18.2 [95% 置信区间 (CI) 15.8–20.9] 和 CON 中的 19.7 (95% CI 17.5–22.2)，差异为 -1.5 (95% CI - 5.0 到 2.0，P = 0.398）。当用全因死亡代替心血管死亡和将中风作为事件添加时，获得了可比较的结果。结论 在参加 ISCHEMIA 的中度或重度心肌缺血的稳定 CAD 患者中，初始 INV 治疗策略并没有比初始 CON 策略更有效地防止净复发事件或净总事件。临床试验注册 ISCHEMIA ClinicalTrials.gov 号，NCT01471522，https://clinicaltrials.gov/ct2/show/NCT01471522。