ISCHEMIA

Purpose: To determine whether an initial invasive strategy of cardiac catheterization and optimal revascularization, if feasible, in addition to OMT, will reduce the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure in participants with SIHD and at least moderate ischemia over an average follow-up of approximately 3.5 years compared with an initial conservative strategy of OMT alone with catheterization reserved for failure of OMT.

Trial Design
COURAGE and BARI 2D, the two largest prior trials comparing coronary revascularization vs. medical therapy in SIHD patients, found that among patients selected on the basis of coronary anatomy after cardiac catheterization, an initial management strategy of coronary revascularization (PCI, PCI or CABG, respectively) did not significantly reduce the primary endpoints of death or MI (COURAGE), or death (BARI 2D) compared with OMT alone. The ISCHEMIA Trial was designed to compare outcomes with an initial invasive vs a conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing.

ISCHEMIA is an NHLBI-supported trial where all 5179 randomized participants received secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy underwent cardiac catheterization only for failure of OMT.

Trial Population:

• Males and females over age 18 with SIHD and at least moderate ischemia
• Of 8518 enrolled patients, 5179 were determined to be eligible based on additional screening and randomized at 320 sites
• Patients with a glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline were excluded from the study
• Participants were 64 years old (median), 23% women, 34% 1726 nonwhite, 16% Hispanic, 41% diabetic, and 90% with a history of angina
• The qualifying stress test modality was stress imaging in 3909 (75%); the remainder were non-imaging ETTs
• Core laboratories judged that the trial-required level of ischemia was met in 85% of randomized participants
• Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79% had multivessel CAD and 87% had left anterior descending (LAD) stenosis (proximal in 47%)

Primary Endpoint(s):

• Composite of CV death, MI, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest

Secondary Endpoint(s):

• The composite of CV death or MI
• Angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire
• All-cause mortality
• Net clinical benefit assessed by including stroke in the primary and secondary composite endpoints
• Individual components of the composite endpoints

Sponsor(s)/Collaborator(s):

Montreal NYU Langone Health, New York University, Stanford University, National Heart, Lung, and Blood Institute (NHLBI), Albany, Stratton VA Medical Center, Cedars-Sinai Medical Center, Columbia University, Duke University, East Carolina University, Emory University, Harvard University, Massachusetts General Hospital, Montreal Heart Institute, University of British Columbia, University of Missouri - Kansas City, Vanderbilt University