Background:The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy.Methods:In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory–interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest).Results:Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61–1.30]; severe ischemia HR, 0.83 [95% CI, 0.57–1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86–1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98–1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06–6.98]) and MI (HR, 3.78 [95% CI, 1.63–8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%–12.4%]), but 4-year all-cause mortality was similar.Conclusions:Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup.Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.

中文翻译：

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基于冠状动脉疾病和缺血严重程度的缺血试验结果


背景：ISCHEMIA 试验（医疗和侵入性方法的健康效果比较国际研究）假设，患有稳定型冠状动脉疾病 (CAD) 和中度或重度缺血的患者将从血运重建中受益。我们调查了 CAD 和缺血严重程度以及试验结果之间的总体关系和管理策略。方法：总共 5179 名中度或重度缺血患者被随机分配至初始侵入性或保守性管理策略。采用盲法、核心实验室解释的冠状动脉计算机断层血管造影来评估随机分组的解剖资格。 CAD 的范围和严重程度按照改良的杜克预后指数进行分类（n=2475，48%）。缺血严重程度由独立核心实验室（核、超声心动图、磁共振成像、运动耐量测试，n=5105，99%）进行解释。我们比较了根据缺血和 CAD 严重程度定义的各亚组的 4 年事件发生率。该分析的主要终点是全因死亡率。次要终点是心肌梗死 (MI)、心血管死亡或 MI，以及试验主要终点（心血管死亡、MI 或因不稳定心绞痛、心力衰竭或复苏性心脏骤停而住院）。 结果：相对于轻度/无缺血，中度缺血和重度缺血均与死亡率增加无关（中度缺血风险比 [HR]，0.89 [95% CI，0.61–1.30]；重度缺血 HR，0.83 [95% CI，0.57–1.21]； P = 0.33 ）。非致命性心梗发生率随着缺血严重程度的加重而增加（中度缺血的 HR，1.20 [95% CI，0.86–1.69] 与轻度/无缺血相比；重度缺血的 HR，1.37 [95% CI，0.98–1.91]； P = 0。04 为趋势， P = NS 经 CAD 调整后）。对于最严重和最不严重的 CAD 亚组，CAD 严重程度的增加与死亡（HR，2.72 [95% CI，1.06–6.98]）和 MI（HR，3.78 [95% CI，1.63–8.78]）相关。缺血严重程度未确定亚组对死亡率、心肌梗死、试验主要终点或心血管死亡或心肌梗死具有治疗益处。在最严重的 CAD 亚组 (n=659) 中，侵入性策略组的 4 年心血管死亡或 MI 发生率较低（差异为 6.3% [95% CI, 0.2%–12.4%]），但 4-年全因死亡率相似。结论：调整 CAD 严重程度后，缺血严重程度与风险增加无关。更严重的 CAD 与风险增加相关。侵入性治疗并未降低任何缺血或 CAD 亚组 4 年时的全因死亡率。注册：URL：https://www.clinicaltrials.gov。唯一标识符：NCT01471522。