International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

BACKGROUND: Evidence supporting a routine invasive practice paradigm for patients with stable ischemic heart disease (SIHD) is outdated.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. DESIGN NARRATIVE: The study protocol is final, and was distributed to sites February 2012. Study protocol v2.0 was approved in January 2014. PARTICIPATING COUNTRIES: North America - Canada - Mexico - USA (~150 sites) South America - Argentina - Brazil - Chile - Peru Asia - China - India - Japan - Singapore - Taiwan - Thailand - Russian Federation Pacifica - Australia - New Zealand Europe - Austria - Belgium - Denmark - France - Germany - Hungary - Italy - Lithuania - Macedonia - Netherlands - Poland - Portugal - Romania - Serbia - Spain - Sweden - UK Middle East - Israel - Saudi Arabia - Turkey

Who is eligible to participate?

Inclusion Criteria: - At least moderate ischemia on an ischemia test - Participant is willing to comply with all aspects of the protocol, including adherence to the assigned strategy, medical therapy and follow-up visits - Participant is willing to give written informed consent - Age ≥ 21 years Exclusion Criteria: - LVEF < 35% - History of unprotected left main stenosis >50% on prior coronary computed tomography angiography (CCTA) or prior cardiac catheterization (if available) - Finding of "no obstructive CAD" (<50% stenosis in all major epicardial vessels) on prior CCTA or prior catheterization, performed within 12 months - Coronary anatomy unsuitable for either PCI or CABG - Unacceptable level of angina despite maximal medical therapy - Very dissatisfied with medical management of angina - History of noncompliance with medical therapy - Acute coronary syndrome within the previous 2 months - PCI within the previous 12 months - Stroke within the previous 6 months or spontaneous intracranial hemorrhage at any time - History of ventricular tachycardia requiring therapy for termination, or symptomatic sustained ventricular tachycardia not due to a transient reversible cause - NYHA class III-IV heart failure at entry or hospitalization for exacerbation of chronic heart failure within the previous 6 months - Non-ischemic dilated or hypertrophic cardiomyopathy - End stage renal disease on dialysis or estimated glomerular filtration rate (eGFR) <30mL/min (not an exclusion criterion for CKD ancillary trial, see CKD ancillary trial, Section 18) - Severe valvular disease or valvular disease likely to require surgery or percutaneous valve replacement during the trial - Allergy to radiographic contrast that cannot be adequately pre-medicated, or any prior anaphylaxis to radiographic contrast - Planned major surgery necessitating interruption of dual antiplatelet therapy (note that patients may be eligible after planned surgery) - Life expectancy less than the duration of the trial due to non-cardiovascular comorbidity - Pregnancy (known to be pregnant; to be confirmed before CCTA and/or randomization, if applicable) - Patient who, in the judgment of the patient's physician, is likely to have significant unprotected left main stenosis (Those who are able to undergo CCTA will have visual assessment of the left main coronary artery by the CCTA core lab) - Enrolled in a competing trial that involves a non-approved cardiac drug or device - Inability to comply with the protocol - Exceeds the weight or size limit for CCTA or cardiac catheterization at the site - Canadian Cardiovascular Society Class III angina of recent onset, OR angina of any class with a rapidly progressive or accelerating pattern - Canadian Cardiovascular Society Class IV angina, including unprovoked rest angina - High risk of bleeding which would contraindicate the use of dual antiplatelet therapy - Cardiac transplant recipient - Prior CABG, unless CABG was performed more than 12 months ago, and coronary anatomy has been demonstrated to be suitable for PCI or repeat CABG to accomplish complete revascularization of ischemic areas (CCC approval required)

Last updated:

4/3/2014

NCT ID:

NCT01471522

IRB Number:

12-007224