New York Universty Grossman School of Medicine (H.R.R.., S.B., J.D.N., J.S.H.).
Weill Cornell Medicine/New York Presbyterian Hospital (L.J.S.).
Circulation. 2021 Sep 28;144(13):1024-1038. doi: 10.1161/CIRCULATIONAHA.120.049755. Epub 2021 Sep 9.
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.
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).
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]; =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]; =0.04 for trend, =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.
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.
ISCHEMIA 试验（国际比较医疗和介入治疗效果研究）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获益。我们研究了 CAD 严重程度和缺血程度与试验结果的关系，包括整体和按治疗策略的关系。
共有 5179 例中度或重度缺血的患者被随机分配到初始介入或保守治疗策略。使用盲法、核心实验室解读的冠状动脉计算机断层扫描血管造影术评估随机分组的解剖学适宜性。采用改良的杜克预后指数（2475 例，48%）对 CAD 的严重程度和严重程度进行分类。通过独立的核心实验室（核医学、超声心动图、磁共振成像、运动耐量试验，5105 例，99%）对缺血严重程度进行解读。我们比较了根据缺血和 CAD 严重程度定义的亚组 4 年的事件发生率。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 和试验主要终点（心血管死亡、MI 或不稳定型心绞痛、心力衰竭或复苏性心脏骤停住院）。
与轻度/无缺血相比，中度缺血或重度缺血均与死亡率增加无关（中度缺血 HR，0.89 [95%CI，0.61-1.30]；重度缺血 HR，0.83 [95%CI，0.57-1.21]；=0.33）。非致死性 MI 发生率随缺血严重程度的恶化而增加（中度缺血 HR，1.20 [95%CI，0.86-1.69]与轻度/无缺血相比；重度缺血 HR，1.37 [95%CI，0.98-1.91]；趋势检验=0.04，=NS 经 CAD 调整后）。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]）有关，最严重的 CAD 亚组与最不严重的 CAD 亚组相比。缺血严重程度并不能确定死亡率、MI、试验主要终点或心血管死亡或 MI 治疗获益的亚组。在最严重的 CAD 亚组（n=659），介入治疗组 4 年的心血管死亡或 MI 发生率较低（差异，6.3% [95%CI，0.2%-12.4%]），但 4 年全因死亡率相似。
在调整 CAD 严重程度后，缺血严重程度与风险增加无关。更严重的 CAD 与风险增加有关。在任何缺血或 CAD 亚组中，介入治疗并不能降低 4 年的全因死亡率。
