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

Overview

Información sobre este estudio

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 ~8000 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

Elegibilidad para la participación

Los requisitos de elegibilidad de los participantes incluyen la edad, el sexo, el tipo y el estadio de la enfermedad, y los problemas de salud o tratamientos previos. Las pautas difieren de un estudio a otro e identifican quiénes pueden o no pueden participar. No hay garantía de que cada persona elegible que desee participar en un ensayo se inscribirá. Comunícate con el equipo del estudio para analizar la elegibilidad del estudio y la posible participación.

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)

More information

Publicaciones

It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. Read More on PubMed
Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. Read More on PubMed
There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials. Read More on PubMed
It is unknown whether preconceived beliefs regarding the need for cardiac catheterization and revascularization in patients with stable ischemic heart disease (SIHD) would preclude a study randomizing patients with significant ischemia to a conservative strategy. Given the widespread practice of performing revascularization in patients with SIHD, we assessed the feasibility of conducting a randomized trial comparing initial invasive and conservative strategies in patients with SIHD and moderate or severe ischemia. Read More on PubMed

Ensayos clínicos