The purpose of the ISCHEMIA trial is to determine the best management strategy for higher-risk patients with stable ischemic heart disease. This is a multicenter randomized controlled trial with a target enrollment of ~5000 patients with at least moderate ischemia on stress imaging. Patients will be assigned at random to a routine invasive strategy (INV) with cardiac catheterization (cath) followed by revascularization plus optimal medical therapy (OMT) or to a conservative strategy (CON) of OMT, with cath and revascularization reserved for those who fail OMT. SPECIFIC AIMS A. Primary Aim The primary aim of the ISCHEMIA trial is to determine whether an initial invasive strategy of cardiac catheterization followed by optimal revascularization, if feasible, in addition to OMT, will reduce the primary composite endpoint of cardiovascular death or nonfatal myocardial infarction in participants with SIHD and at least moderate ischemia over an average follow-up of approximately 4 years compared with an initial conservative strategy of OMT alone with catheterization reserved for failure of OMT. The primary endpoint is time to centrally adjudicated cardiovascular death or nonfatal myocardial infarction. B. Secondary Aims Major: To compare angina-related quality of life between groups. Other secondary aims include: a) comparing the incidence of all-cause death; the components of the primary endpoint; the composite endpoint of cardiovascular death, myocardial infarction, or hospitalization for unstable angina, resuscitated cardiac arrest, or heart failure; stroke; and stroke combined with cardiovascular death, myocardial infarction, or hospitalization for unstable angina, resuscitated cardiac arrest, or heart failure between randomized groups; and b) comparing health resource utilization, costs, and cost-effectiveness between groups. Condition: Coronary Disease Procedure: Coronary CT Angiogram Procedure: Cardiac catheterization Phase: Phase III Condition: Cardiovascular Diseases Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions Phase: Phase III Condition: Heart Diseases Procedure: Coronary Artery Bypass Surgery Phase: Phase III
Evidence supporting a routine invasive practice paradigm for patients with stable ischemic heart disease (SIHD) is outdated. In strategy trials conducted in the 1970s, coronary artery bypass grafting (CABG) improved survival as compared with no CABG in SIHD patients with high-risk anatomic features. The relevance of these studies today is speculative because contemporary secondary prevention—aspirin, beta-blockers, statins, ACE inhibitors, and lifestyle interventions—were used minimally if at all. Subsequent trials have compared percutaneous coronary intervention (PCI) with medical therapy, as PCI has replaced CABG as the dominant method of revascularization for SIHD. To date, PCI has not been shown to reduce death or myocardial infarction (MI) compared with medical therapy in SIHD patients.
COURAGE and BARI 2D, the two largest trials comparing coronary revascularization vs. medical therapy in SIHD patients, found that among patients selected on the basis of coronary anatomy after cath, an initial management strategy of coronary revascularization (PCI, PCI or CABG, respectively) did not reduce the primary endpoints of death or MI (COURAGE), or death (BARI 2D) compared with OMT alone. These data suggest, but do not prove, that routine cath--which often leads to ad hoc PCI through the diagnostic-therapeutic cascade--may not be required in SIHD patients. However, most patients enrolled in COURAGE and BARI 2D who had ischemia level documented at baseline had only mild or moderate ischemia, leaving open the question of the appropriate role of cath and revascularization among higher risk patients with more severe ischemia. Observational data suggest that revascularization of patients with moderate-to-severe ischemia is associated with a lower mortality than medical therapy alone, but such data cannot establish a cause and effect relationship. In clinical practice only about half such patients are referred for cath, indicating equipoise. Furthermore, analysis of outcomes for 468 COURAGE patients with moderate-to-severe ischemia at baseline did not reveal a benefit from PCI. This issue cannot be resolved using available data because all prior SIHD strategy trials enrolled patients after cath, introducing undefined selection biases (e.g., highest risk patients not enrolled) and making translation of study results problematic for clinicians managing patients who have not yet had cath.
A clinical trial in SIHD patients uniformly at higher risk (which could not have been performed before COURAGE and BARI 2D results were available) is needed to inform optimal management for such patients.
The study protocol is final, and was distributed to sites February 2012. Study protocol v2.0 was approved in January 2014.
Cardiovascular Diseases Coronary Disease Coronary Artery Disease Heart Diseases Myocardial Ischemia
Open to people ages 21 years and up
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