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

• ClinicalTrials.gov Identifier: NCT01471522
• Recruitment Status: Completed
• First Posted: November 15, 2011
• Results First Posted: July 23, 2020
• Last Update Posted: June 1, 2023
• Sponsor: NYU Langone Health
• Collaborators: 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
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

The purpose of the ISCHEMIA trial is to determine the best management strategy for higher-risk patients with stable ischemic heart disease (SIHD). This is a multicenter randomized controlled trial with 5179 randomized participants with moderate or severe ischemia on stress testing. A blinded coronary computed tomography angiogram (CCTA) was performed in most participants with eGFR ≥60 mL/min/1.73m2 to identify and exclude participants with either significant unprotected left main disease (≥50% stenosis) or those without obstructive CAD (<50% stenosis in all major coronary arteries). Of 8518 participants enrolled, those that had insufficient ischemia, ineligible anatomy demonstrated on CCTA or another exclusion criterion, did not go on to randomization. Eligible participants were then assigned at random to a routine invasive strategy (INV) with cardiac catheterization followed by revascularization, if feasible, plus optimal medical therapy (OMT) or to a conservative strategy (CON) of OMT, with cardiac catheterization 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, nonfatal myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure in participants with SIHD and moderate or severe 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.

B. Secondary Aims Secondary aims are to determine whether an initial invasive strategy compared to a conservative strategy will improve: 1) the composite of CV death or MI; 2) angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire; 3) all-cause mortality; 4) net clinical benefit assessed by including stroke in the primary and secondary composite endpoints; and 5) individual components of the composite endpoints.

Condition: Coronary Disease Procedure: Coronary CT Angiogram Procedure: Cardiac catheterization Phase: Phase III per NIH

Condition: Cardiovascular Diseases Procedure: Angioplasty, Transluminal, Percutaneous Coronary, other catheter-based interventions Phase: Phase III per NIH

Condition: Heart Diseases Procedure: Coronary Artery Bypass Surgery Phase: Phase III per NIH

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases; Coronary Disease; Coronary Artery Disease; Heart Diseases; Myocardial Ischemia	Procedure: cardiac catheterization; Procedure: coronary artery bypass graft surgery; Procedure: percutaneous coronary intervention; Behavioral: Lifestyle; Drug: Medication	Not Applicable

Detailed Description:

BACKGROUND:

Evidence supporting a routine invasive practice paradigm for patients with 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 cardiac catheterization, 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 cardiac catheterization--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 severity documented at baseline had only mild or moderate ischemia, leaving open the question of the appropriate role of cardiac catheterization 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 cardiac catheterization, 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 cardiac catheterization, 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 cardiac catheterization.

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, INCLUDING MODIFICATIONS DURING THE TRIAL

Primary Endpoint

A composite of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure was proposed as the primary endpoint in the application that was funded by NLHBI, with a secondary endpoint of CV death or MI. Study protocol version 1.0 was finalized on January 18, 2012 after review and approval by the protocol review committee (DSMB) with the primary endpoint specified as the composite of CV death or MI. Regarding the final status of the primary endpoint, the protocol stated:

"To ensure that the primary analysis is well-powered and useful, a prospective plan to allow extending follow-up and/or changing the primary endpoint based on aggregate event rate data will be established prior to the first review of unblinded trial data. At a designated time during the trial, an analysis will be conducted to estimate the overall aggregate primary endpoint event rate and project the final number of observed events. If the estimated unconditional power (i.e. based on aggregate event rate data; not by treatment group) is less than the originally targeted 90%, then one or more of the following options will be considered:

1. Extend follow-up to allow more events to accrue.
2. Change the primary endpoint to one that occurs more frequently. The current primary endpoint would become a secondary endpoint. The proposed new primary endpoint would be the composite of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure.
3. Follow the recommendation of an independent advisory panel. An independent advisory panel, separate from the DSMB, will be convened for the purpose of reviewing unconditional power estimates and making a recommendation to the NHLBI Director. Members of this panel will not have access to unblinded data by treatment group or other data that may bias their recommendation." All 5 event types were adjudicated throughout the trial. Study protocol v2.0 (January 2014) allowed ischemia eligibility by non-imaging exercise stress test if more stringent (≥70% stenosis) CCTA criteria were met. The 2016 protocol addendum describes the NHLBI-approved reduction in sample size and extension of recruitment and follow-up due to slower than projected recruitment.

The pre-specified first analysis for monitoring and projecting the final aggregate number of primary endpoint events was conducted in 2015. In 2016, the projected need to increase the power by extending follow-up and elevating the 5-component secondary endpoint to become primary was discussed at Steering Committee and Investigator meetings and communicated by email.

An Independent Advisory Panel convened by NHLBI met in May 2017, and in June 2017 NHLBI approved the Independent Advisory Panel's recommendation to elevate the 5-component secondary endpoint to become primary and retain the 2-component composite as a key secondary endpoint. The panel also recommended extension of follow-up. This was communicated to the Steering Committee and Investigators at August and November 2017 meetings and by email. The last visit date was June 30, 2019.

A statistical plan developed for the Independent Advisory Panel process in 2012 specified that a decision about changing the primary endpoint would be targeted to occur before 75% of the final number of primary endpoint events had accrued. Although the final number of primary endpoint events was unknown during the course of the trial, estimates performed at the time of the Advisory Panel meeting suggested that the ratio of accrued endpoint events to final endpoint events was below 50%. See Maron DJ et al. Am Heart J. 2018 201:124-135. PMC6005768 for additional details about modifications to the trial while it was being conducted.

Analysis of Patients' Health Status as a Key Secondary Endpoint

A key secondary objective of the ISCHEMIA trial is to compare the quality of life outcomes-patients' symptoms, functioning and well-being-between those assigned to an invasive strategy as compared with a conservative strategy. In the protocol, angina frequency and disease-specific quality of life measured by the Seattle Angina Questionnaire (SAQ) Angina Frequency and Quality of Life scales, respectively, are described as the tools that will be used to make this comparative assessment. Recent work has indicated that it is possible to combine the information from the individual domain scores in the SAQ into a new Summary Score that captures the information from the SAQ Angina Frequency, Physical Limitation and Quality of Life scales into a single overall score. The advantages of using a summary score as the primary measure of QOL effects of a therapy are a single primary endpoint comparison rather than two or three (eliminating concerns some may have about multiple comparisons) and a more intuitive holistic (patient-centric) interpretation of the effectiveness results. With these advantages in mind, the ISCHEMIA leadership has agreed that the SAQ Summary Score will be designated as the primary way this outcome for this key secondary endpoint of the ISCHEMIA trial will be analyzed and interpreted, with the individual SAQ scores being used in a secondary, explanatory and descriptive role.

PARTICIPATING COUNTRIES:

North America:

Canada; Mexico; USA

South America:

Argentina; Brazil; Peru

Asia:

China; India; Japan; Malaysia; Singapore; Taiwan; Thailand; Russian Federation

Pacifica:

Australia; New Zealand

Europe:

Austria; Belgium; France; Germany; Hungary; Italy; Lithuania; Macedonia; Netherlands; Poland; Portugal; Romania; Serbia; Spain; Sweden; Switzerland; UK

Middle East:

Egypt; Israel; Saudi Arabia

Africa:

South Africa

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5179 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)
• Study Start Date: July 2012
• Actual Primary Completion Date: June 30, 2019
• Actual Study Completion Date: May 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Invasive Strategy (INV); Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.	Procedure: cardiac catheterization; Narrowed blood vessels can be opened without surgery using stents or can be bypassed with surgery. To determine which is the best approach for you the doctor needs to look at your blood vessels to see where the narrowings are and how much narrowing there is. This is done by a procedure known as a cardiac catheterization.; Other Name: cath; Procedure: coronary artery bypass graft surgery; Artery narrowing is bypassed during surgery with a healthy artery or vein from another part of the body. This is known as coronary artery bypass grafting, or CABG (said, "cabbage"). The surgery creates new routes around narrowed and blocked heart arteries. This allows more blood flow to the heart.; Other Name: CABG; Procedure: percutaneous coronary intervention; Percutaneous coronary intervention may be done as part of the cardiac catheterization procedure. With this procedure a small, hollow, mesh tube (stent) is inserted into the narrowed part of the artery. The stent pushes the plaque against the artery wall, and opens the vessel to allow better blood flow.; Other Name: PCI; Behavioral: Lifestyle; diet, physical activity, smoking cessation; Other Name: Behavior change; Drug: Medication; antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies; Other Name: Pharmacologic Therapy
Active Comparator: Conservative Strategy; Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms.	Behavioral: Lifestyle; diet, physical activity, smoking cessation; Other Name: Behavior change; Drug: Medication; antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies; Other Name: Pharmacologic Therapy

Outcome Measures

Primary Outcome Measures :

1. Primary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest [ Time Frame: 3.2 year follow-up (median) ]
2. Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest) [ Time Frame: 5 years ]
   This measure represents the estimated cumulative probability of experiencing the primary endpoint within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur).
3. Number of Participants That Experienced Death From Cardiovascular Causes or Myocardial Infarction [ Time Frame: 5 years ]
4. Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction [ Time Frame: 5 years ]
   This measure represents the estimated cumulative probability of experiencing Death from cardiovascular causes or myocardial infarction within the indicated timeframe in each treatment group. The interpretation of the measure is similar to Kaplan-Meier event rates. Estimates are expressed as percentages ranging from 0% (endpoint is certain not to occur) to 100% (endpoint is certain to occur).
5. Number of Participants That Experienced Death From Any Cause [ Time Frame: 5 years ]
6. Cumulative Event Rate of Death From Any Cause [ Time Frame: 5 years ]
7. Number of Participants That Experienced Myocardial Infarction [ Time Frame: 5 years ]
8. Cumulative Event Rate of Myocardial Infarction [ Time Frame: 5 years ]
9. Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative [ Time Frame: 5 years ]
   The primary composite outcome includes death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.
10. Estimated Difference in Cumulative Event Rate of Death From Cardiovascular Causes: Invasive Minus Conservative or Myocardial Infarction Between Invasive and Conservative Strategies [ Time Frame: 5 years ]
11. Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative [ Time Frame: 5 years ]
12. Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative [ Time Frame: 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• At least moderate ischemia on a qualifying stress 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)

Contacts and Locations

Locations

United States, Alabama

UAB Vascular Biology and Hypertension Program

Birmingham, Alabama, United States, 35294

United States, Arizona

Yuma Regional Medical Center

Yuma, Arizona, United States, 85364

United States, California

Cedars Sinai Medical Center

Beverly Hills, California, United States, 90211

UCSF - Fresno Community Regional Medical Center

Fresno, California, United States, 93721

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States, 90095

University of California Irvine Medical Center

Orange, California, United States, 92868

Palo Alto Medical Foundation Research Institute

Palo Alto, California, United States, 94087

VA Palo Alto HealthCare System

Palo Alto, California, United States, 94550

Kaiser Permanente San Jose

San Jose, California, United States, 94538

Coastal Heart Medical Group

Santa Ana, California, United States, 92704

Stanford University School of Medicine

Stanford, California, United States, 94305

Torrance Memorial Medical Center

Torrance, California, United States, 90505

United States, Colorado

South Denver Cardiology Associates, P.C.

Littleton, Colorado, United States, 80120

Medical Center of the Rockies

Loveland, Colorado, United States, 80538

United States, Connecticut

VA Connecticut Healthcare System

West Haven, Connecticut, United States, 06111

United States, Florida

Daytona Heart Group

Daytona Beach, Florida, United States, 32114

Malcom Randall VAMC

Gainesville, Florida, United States, 32608

Mayo Clinic Florida

Jacksonville, Florida, United States, 32224

Cardiovascular Center of Sarasota

Sarasota, Florida, United States, 34239

Sarasota Memorial Hospital

Sarasota, Florida, United States, 34239

University of South Florida

Tampa, Florida, United States, 33606

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

Atlanta VA Medical Center

Decatur, Georgia, United States, 30033

United States, Illinois

Advanced Heart Care Group

Fairview Heights, Illinois, United States, 62208

Loyola University Medical Center

Maywood, Illinois, United States, 60153

United States, Indiana

Indiana University/Krannert Institute of Cardiology

Indianapolis, Indiana, United States, 46202

United States, Iowa

Midwest Cardiovascular Research Foundation

Davenport, Iowa, United States, 52803

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536

Lexington VA Medical Center

Lexington, Kentucky, United States, 42503

University of Louisville

Louisville, Kentucky, United States, 40292

United States, Louisiana

Cardiovascular Specialists of Southwest Louisiana

Lake Charles, Louisiana, United States, 70601

United States, Maryland

University of Maryland Medical Center

Baltimore, Maryland, United States, 21201

NIH Heart Center at Suburban Hospital

Bethesda, Maryland, United States, 20814

Walter Reed National Military Medical Center

Bethesda, Maryland, United States, 20889

United States, Massachusetts

Brigham & Women's Hospital, Harvard Medical School

Boston, Massachusetts, United States, 02115

Boston Medical Center

Boston, Massachusetts, United States, 02118

VA Boston Healthcare System

West Roxbury, Massachusetts, United States, 02132

Saint Vincent Hospital at Worcester Medical Center

Worcester, Massachusetts, United States, 01608

United States, Michigan

Henry Ford Health System

Detroit, Michigan, United States, 48202

Spectrum Health

Grand Rapids, Michigan, United States, 49503

Covenant Medical Center, Inc.

Saginaw, Michigan, United States, 01876

Providence - Providence Park Hospital

Southfield, Michigan, United States, 48075

Michigan Heart, PC

Ypsilanti, Michigan, United States, 48197

United States, Minnesota

Minneapolis VAMC

Minneapolis, Minnesota, United States, 55417

University of Minnesota

Minneapolis, Minnesota, United States, 55455

Mayo Clinic

Rochester, Minnesota, United States, 55905

HealthEast Saint Joseph's Hospital

Saint Paul, Minnesota, United States, 55102

United States, Missouri

Saint Luke's Hospital

Kansas City, Missouri, United States, 64111

Kansas City VA Medical Center

Kansas City, Missouri, United States, 64128

United States, New Jersey

Englewood Hospital and Medical Center

Englewood, New Jersey, United States, 07631

AtlantiCare Regional Medical Center

Pomona, New Jersey, United States, 08240

Hackensack University Medical Center

Saddle Brook, New Jersey, United States, 07663

United States, New York

Albany Medical Center Hospital

Albany, New York, United States, 12208

Samuel Stratton VA Medical Center of Albany NY

Albany, New York, United States, 12208

Capital Cardiology Associates

Albany, New York, United States, 12211

NYU-HHC Lincoln Medical and Mental Health Center

Bronx, New York, United States, 10451

Jacobi Medical Center

Bronx, New York, United States, 10461

NYU-HHC Kings County Hospital Center

Brooklyn, New York, United States, 11203

New York -Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York, United States, 11215

NYU-HHC Woodhull Hospital

Brooklyn, New York, United States, 11229

Coney Island Hospital

Brooklyn, New York, United States, 11235

NYP Medical Medical Group Hudson Valley Cardiology

Cortlandt Manor, New York, United States, 10567

New York University - Langone Cardiovascular Associates

Flushing, New York, United States, 11355

Mid Valley Cardiology

Kingston, New York, United States, 12401

Northwell Health - Manhasset

Manhasset, New York, United States, 11030

NYU Winthrop

Mineola, New York, United States, 11501

VA New York Harbor Health Care System

New York, New York, United States, 10010

Beth Israel Medical Center

New York, New York, United States, 10016

NYU Langone Medical Center-Bellevue Hospital

New York, New York, United States, 10016

NYU New York Medical Associates

New York, New York, United States, 10022

Mount Sinai Saint Luke's Hospital

New York, New York, United States, 10025

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Columbia University Medical Center

New York, New York, United States, 10032

University of Rochester

Rochester, New York, United States, 14642

Cardiology Associates of Schenectady P.C.

Schenectady, New York, United States, 12309

United States, North Carolina

Asheville Cardiology Associates

Asheville, North Carolina, United States, 28803

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, North Dakota

Sanford Health

Fargo, North Dakota, United States, 58122

United States, Ohio

Cincinnati VA Medical Center

Cincinnati, Ohio, United States, 45220

Louis Stokes Cleveland Veterans Affairs Medical Center

Cleveland, Ohio, United States, 44106

Ohio Health Grant Medical Center

Columbus, Ohio, United States, 43215

United States, Oklahoma

Oklahoma Heart Institute

Tulsa, Oklahoma, United States, 74133

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97201

Providence Heart and Vascular Institute

Portland, Oregon, United States, 97225

United States, Pennsylvania

Saint Luke's Hospital and Health Network

Bethlehem, Pennsylvania, United States, 18018

Holy Spirit Hospital Cardiovascular Institute

Camp Hill, Pennsylvania, United States, 17011

Doylestown Health Cardiology

Doylestown, Pennsylvania, United States, 18901

Conemaugh Valley Memorial Hospital

Johnstown, Pennsylvania, United States, 15905

United States, Rhode Island

Miriam Hospital

Providence, Rhode Island, United States, 02906

Kent Hospital

Warwick, Rhode Island, United States, 02886

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

Saint Thomas Hospital

Nashville, Tennessee, United States, 373203

United States, Texas

V.A. North Texas Health Care System

Dallas, Texas, United States, 75216

Baylor College of Medicine

Houston, Texas, United States, 77030

Baylor St. Luke's Medical Center

Houston, Texas, United States, 77030

Houston Heart & Vascular Associates

Houston, Texas, United States, 77339

Baylor Research Institute at Legacy Heart Center

Plano, Texas, United States, 75024

The Heart Hospital Baylor

Plano, Texas, United States, 75093

Audie Murphy V.A.

San Antonio, Texas, United States, 78229

Medicus Alliance Clinical Research Org., Inc.

Sugar Land, Texas, United States, 77478

Wichita Falls Heart Clinic

Wichita Falls, Texas, United States, 76301

United States, Utah

Salt Lake City VA Medical Center

Salt Lake City, Utah, United States, 84148

United States, Vermont

VAMC-White River Junction

White River Junction, Vermont, United States, 05009

United States, Virginia

Cardiovascular Associates, Ltd.

Chesapeake, Virginia, United States, 23320

Stroobants Cardiovascular Center

Lynchburg, Virginia, United States, 24501

Winchester Cardiology and Vascular Medicine, PC

Winchester, Virginia, United States, 22601

United States, Washington

University of Washington Medical Center

Bellevue, Washington, United States, 98004

United States, Wisconsin

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States, 54601

Argentina

Hospital Italiano Regional del Sur Bahia Blanca

Bahia Blanca, Buenos Aires, Argentina, 8000

Fundacion Favaloro

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1093AAS

Instituto Medico DAMIC

Cordoba, CBA, Argentina, 5009

Clinica Del Prado

Cordoba, Argentina, 5000

Clinica Romagosa and Clinica De La Familia

Cordoba, Argentina, 5000

Clínica Privada Vélez Sarsfield

Cordoba, Argentina, 5000

Australia, New South Wales

John Hunter Hospital

New Lambton Heights, New South Wales, Australia, 2305

Australia, South Australia

Flinders Medical Centre

Adelaide, South Australia, Australia, 5042

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia, 5011

Australia, Western Australia

Royal Perth Hospital

Perth, Western Australia, Australia, 6000

Austria

LKH Graz West Austria

Graz, Stmk, Austria, 8020

Medical University of Vienna, Department of Cardiology

Vienna, Wien, Austria, 1090

Wilhelminen Hospital Vienna

Vienna, Wien, Austria, A-1160

Belgium

University Hospital Leuven

Leuven, Brabant, Belgium, 3000

Brazil

Fundacao Bahiana de Cardilogia

Salvador, Bahia, Brazil, 41810-010

Hospital Lifecenter

Belo Horizonte, Minas Gerais, Brazil, 30110-921

Hospital Maternidade e Pronto Socorro Santa Lucia

Pocos de Caldas, Minas Gerais, Brazil, 37701-045

Quanta Diagnostico & Terapia

Curitiba, Parana, Brazil, 80045-170

Hospital Cardiologico Costantini

Curitiba, Parana, Brazil, 80320-320

Hospital Pró-Cardíaco

Botafogo, Rio De Janeiro, Brazil, 22280-020

Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sol

Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000

Instituto de Cardiologia de Porto Alegre

Porto Alegre, Rio Grande Do Sul, Brazil, 90620-001

Hospital Sao Vicente de Paulo

Fundo, RS, Brazil, 99010080

Hospital de Clinicas de Porto Alegre

Porto Alegre, RS, Brazil, 90035-903

Instituto Dante Pazzanese de Cardiologia

Ibirapuera, Sao Paulo, Brazil, 04012-909

Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirao Preto, Sao Paulo, Brazil, 14048-900

Hospital TotalCor

Sao Paulo, SP, Brazil, 1418100

Hospital da Bahia

Salvador, Brazil, BA, 41820-011

Unifesp - Hospital Sao Paulo

Sao Paulo, Brazil, 04025-011

Heart Institute (InCor) University of São Paulo

Sao Paulo, Brazil, 05403-000

Hospital Celso Pierro

Sao Paulo, Brazil, 13059-740

Canada, Alberta

University of Calgary

Calgary, Alberta, Canada, T2N 2T9

University of Alberta

Edmonton, Alberta, Canada, T6G 2B7

Canada, British Columbia

Vancouver General Hospital

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Ontario

West Lincoln Memorial Hospital

Grimsby, Ontario, Canada, L3M 1P3

Hamilton General Hospital

Hamilton, Ontario, Canada, L8L 2X2

London Health Sciences Centre

London, Ontario, Canada, N6A 5A5

Dixie Medical Group

Mississauga, Ontario, Canada, L4W 0C2

Dr. James Cha

Oshawa, Ontario, Canada, L1J 2K1

Scarborough Cardiology Research

Scarborough, Ontario, Canada, M1E 5E9

Saint Catharines General Hospital

St. Catharines, Ontario, Canada, L2S0A9

St. Michael's Hospital

Toronto, Ontario, Canada, M5B 1W8

Women's College Hospital

Toronto, Ontario, Canada, M5G 1N8

University Health Network

Toronto, Ontario, Canada, M5G 2C4

Northwest GTA Cardiovascular and Heart Rhythm Program

Vaughan, Ontario, Canada, L4H0P6

Canada, Quebec

Montreal Heart Institute

Montreal, Quebec, Canada, H1T 1C8

Centre Intégré Universitaire de Santé et de Services Sociaux du Montréal

Montréal, Quebec, Canada, H4J 1C5

CISSSL - Hopital Pierre-Le Gardeur

Terrebonne, Quebec, Canada, J6V 2H2

Centre Hospitalier de Regional Trois-Rivieres

Trois-Rivieres, Quebec, Canada, G8Z 3R9

Canada

University of Ottawa Heart Institute

Ottawa, Canada, K1Y 4W7

China, Beijing

Beijing Chao-yang Hospital, Capital Medical University

Beijing, Beijing, China, 100020

Chinese Academy of Medical Sciences, Fuwai Hospital

Beijing, Beijing, China, 100037

Peking Union Medical College Hospital

Beijing, Beijing, China, 100730

China, Chaoyang

Beijing Anzhen Hospital

Beijing, Chaoyang, China, 100029

China, Fangshan

Liangxiang Hospital, Beijing Fangshan District

Beijing, Fangshan, China, 102401

China, Guangdong

Guangdong General Hospital

Guangzhou, Guangdong, China, 510100

China, Hebei

Tangshan Gongren Hospital

Tangshan, Hebei, China, 063000

China, Henan

The Second Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China, 450014

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China, 450052

China, Hubei

Tongji Medical College

Wuhan, Hubei, China, 430030

Wuhan Asia Heart Hospital

Wuhan, Hubei, China

Wuhan Union Hospital, Tongji Medical College, Huazhong Science and Tech University

Wuhan, Hubei, China

China, Liaoning

Affiliated Zhongshan Hospital of Dalian University

Dalian, Liaoning, China, 116001

China, Shandong

Affiliated Hospital of Jining Medical University

Jining, Shandong, China, 272000

Qingdao Fuwai Hospital

Qingdao, Shandong, China, 266071

China, Shanxi

Shanxi Cardiovascular Hospital

Taiyuan, Shanxi, China, 030024

Shanxi Provincial People's Hospital

Xian, Shanxi, China, 710000

China, Tianjing

TEDA International Cardiovascular Hospital

Tianjing, Tianjing, China, 300457

China, Xinjiang

First Affiliated Hospital of Xinjiang Medical University

Urumqi, Xinjiang, China, 830054

China, Zhejiang

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China, 310009

Egypt

Cairo University

Cairo, Egypt, 11562

France

C.H. Louis Pasteur

Chatres, Centre, France, 28018

Ambroise Pare Hospital

Boulogne, Ile De France, France, 92100

Centre Hospitalier Sud Francilien

Corbeil-Essonnes cedex, Ile De France, France, 91100

Antoine-Beclere Hospital

Clamart Cedex, Ile-de-France, France, 92141

Bichat Hospital

Paris, Ile-de-France, France, 75018

Grenoble University Hospital

Grenoble, Isere, France, 38700

Centre Hospitalier Universitaire d'Angers

Angers Cedex 9, Pays De La Loire, France, 49933

Germany

Robert-Bosch-Krankenhaus

Stuttgart, BW, Germany, 70376

Universitatsklinikum Bonn

Bonn, NRW, Germany, 53105

Praxisklinik Herz Und Gefaesse

Dresden, Saxony, Germany, D-01099

University Hospital Jena

Jena, Thuringia, Germany, 07747

Hungary

University of Szeged

Szeged, Szeged Megyei Varos, Hungary, 6720

Eszszk- Szent Istvan Hospital

Budapest, Hungary, 1097

Military Hospital, Budapest

Budapest, Hungary, 1117

Heart and Vascular Center, Semmelweis University

Budapest, Hungary, 1122

George Gottsegen National Institute of Cardiology

Budapest, Hungary, H-1096

India

CARE Hospital

Hyderabad, Andhra Pradesh, India, 500034

Gurunanak CARE Hospital

Hyderabad, AP, India, 500020

Dr Ram Manohar Lohia Hospital

New Delhi, Delhi, India, 110001

Fortis Escort Heart Institute

New Delhi, Delhi, India, 110025

Batra Hospital and Medical Research Centre (BHMRC)

New Delhi, Delhi, India, 110062

Fortis Healthcare Fl.t Lt. Rajan Dhall Hospital

New Delhi, Delhi, India, 110070

Sri Jayadeva Institute of Cardiovascular Sciences and Research

Bangalore, Karnataka, India, 560069

Government Medical College

Calicut, Kerala, India, 673008

MOSC Medical College Hospital, Kolenchery

Kolenchery, Kerala, India, 682311

Sree Chitra Tirunal Institute for Medical Sciences and Technology

Trivandrum, Kerala, India, 695011

Ruby Hall Clinic,Grant Medical Foundation

Pune, Maharashtra, India, 411001

KEM Hospital Pune

Pune, Maharashtra, India, 411011

Hero DMC Heart Institute, Dayanand Medical College and Hospital

Ludhiana, Punjab, India, 141001

Apollo Research and Innovation

Chennai, Tamil Nadu, India, 600081

Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)

Pondicherry, Tamil Nadu, India, 605006

CARE Nampally

Hyderabad, Telangana, India, 500001

Apollo Research & Innovations

Hyderabad, Telangana, India, 600081

King George's Medical University, Department of Cardiology

Lucknow, Uttar Pradesh, India, 226003

All India Institute of Medical Sciences

New Delhi, India, 110029

Israel

Rambam Medical Center

Haifa, Israel, 31096

Assuta Medical Centers

Tel-Aviv, Israel, 67891

Italy

AORN Dei Colli "V. Monaldi" UOC Cardiologia Università della Campania "L.Vanvitelli"

Napoli, Campania, Italy, 80131

Ospedale "G.B. Morgagni - L. Pierantoni" Forli (AUSL della Romagna)

Forli, Emilia-Romagna, Italy, 47100

IRCCS "Casa Sollievo della Sofferenza"

San Giovanni Rotondo, FG, Italy, 71013

Cardiology and CCU - Ospedali Riuniti Ancona

Ancona, Marche, Italy, 60020

Policlinico di Monza, Monza MB

Monza, MB, Italy, 20900

Humanitas Research Hospital, Rozzano (MI)

Rozzano, Milano, Italy, 20089

Azienda Ospedaliera S. Croce e Carle

Cuneo, Piemonte, Italy, 12100

UO Cardiologia Ospedale SS Cosma e Damiano

Pescia, Tuscany, Italy, 54100

Azienda Servizi Sanitaria n.3 Alto Friuli-Collinare-Medio Friuli

Tolmezzo, Udine, Italy, 33028

University of Padua- Cardiology Clinic

Padua, Veneto, Italy, 35100

Ospedale Regionale Umberto Parini

Aosta, Italy, 11100

Clinica Mediterranea

Naples, Italy, 80121

Ospedale di Circolo e Fondazione Macchi

Varese, Italy, 21100

Japan

National Cerebral and Cardiovascular Center

Suita-shi, Osaka, Japan, 565-8565

Saitama Medical University

Hidaka, Saitama, Japan, 350-0495

Keio University Hospital

Shinjuku-Ku, Tokyo, Japan, 160-8582

Lithuania

Vilnius University Hospital Santariskes Clinic

Vilnius, Lithuania, LT-08661

Malaysia

Institut Jantung Negara

Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50400

Mexico

Instituto Mexicano del Seguro Social

Benito Juarez, DF, Mexico, 3100

Instituto Nacional de Cardiología "Ignacio Chávez"

Mexico City, Distrito Federal, Mexico, 14080

Netherlands

Cardio Research Hartcentrum OLVG

Amsterdam, NH, Netherlands, 1091 AC

Radboudumc

Nijmegen, Netherlands, 6500 HB

Isala Klinieken

Zwolle, Netherlands, 8025 AB

New Zealand

Waikato Hospital

Hamilton, Waikato, New Zealand, 3240

Auckland City Hospital

Auckland, New Zealand, 1142

North Macedonia

University Clinic of Cardiology

Skopje, Republic Of Macedo, North Macedonia, 1000

Peru

Instituto Neuro Cardiovascular De Las Americas

Miraflores, Lima, Peru, 18

Poland

T.Marciniak Hospital

Wrocław, Dolny Śląsk, Poland, 54-090

Cardiology Clinic, Medical University in Lodz

Lodz, Lodzkie, Poland, 91-425

Department of Coronary Disease, John Paul II Hospital, Jagiellonian University Medical College

Krakow, Maopolskie, Poland, 31-200

Institute of Cardiology, Warsaw

Warsaw, Mazovian, Poland, 04-628

Coronary and Structural Heart Diseases Department, Institute of Cardiology

Warsaw, Mazowieckie, Poland, 04-628

Department of Interventional Cardiology & Angiology, Institute of Cardiology

Warsaw, Mazowieckie, Poland, 04-628

Medical University of Warsaw

Warsaw, Mazowieckie, Poland, PL-02-097

Department of Internal Medicine and Cardiology, Infant Jesus Teaching Hospital, Medical University of Warsaw

Warszawa, Mazowieckie, Poland, 02-005

University Hospital in Bialystok

Bialystok, Podlaskie, Poland, 15-276

Medical University of Silesia, School of Medicine with the Division of Dentistry, Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Silesian Center for Heart Diseases

Zabrze, Wojewodztwo Slaskie, Poland, 41-800

Szpital Kliniczny Przemienienia Pańskiego

Poznan, Poland, 61-848

Military Hospital / Medical University

Wroclaw, Poland, 50-981

Portugal

Hospital de Santa Marta

Lisboa, Portugal, 1150-291

Santa Maria University Hospital, Cardiology Department, CHLN

Lisbon, Portugal, 1649-028

Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE

Vila Nova de Gaia, Portugal, 4434-502

Romania

Emergency County Hospital Baia Mare

Baia Mare, Romania, 021967

Emergency Institute of Cardiovascular Diseases ''Prof. Dr. C. C. Iliescu''

Bucharest, Romania, 022328

Russian Federation

National Medical Research Center for Cardiovascuar Surgery

Moscow, Gorod Moskva, Russian Federation, 121552

E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation

Novosibirsk, Novosibirskaya Oblast, Russian Federation, 630055

North-Western State Medical University

Saint Petersburg, Russian Federation, 199106

Federal Almazov North-West Medical Research Centre

Saint-Petersburg, Russian Federation, 197341

Saudi Arabia

King AbdulAziz Cardiac Center

Riyadh, Central Province, Saudi Arabia, 11426

Serbia

Institute of Cardiovascular Diseases Vojvodina, Sremska Kamenica, Serbia and Faculty of Medicine, University of Novi Sad

Sremska Kamenica, Vojvodina, Serbia, 21204

Clinical Center of Serbia

Belgrade, Serbia, 11000

Faculty of Medicine, University of Belgrade; Cardiology Clinic, Clinical Center of Serbia

Belgrade, Serbia, 11000

University Clinical Hospital Zvezdara

Belgrade, Serbia, 11000

University Hospital Center Bezanijska Kosa

Belgrade, Serbia, 11000

Clinical Center Kragujevac

Kragujevac, Serbia, 11000

Clinic for Cardiovascular Diseases, Clinical Center Nis

Nis, Serbia, 18000

Singapore

National University Heart Center Singapore

Singapore, Singapore, 119228

National Heart Centre Singapore

Singapore, Singapore, 169609

Tan Tock Seng Hospital

Singapore, Singapore, 308433

South Africa

Groote Schuur Hospital / University of Cape Town

Cape Town, Western Cape, South Africa, 7945

Spain

Hospital Clinico Universitario de Santiago

Santiago de Compostela, La Coruna, Spain, 15706

Complexo Hospitalario Universitario A Coruña (CHUAC) Sergas, Department of Cardiology. INIBIC A Coruña. CIBER-CV. Universidad de A Coruña, Spain

A Coruna, Spain, 15008

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain, 08025

Hospital De Bellvitge

Barcelona, Spain, 08907

Hospital General Universitario Gregorio Maranon

Madrid, Spain, 28007

Hospital La Paz. IdiPaz

Madrid, Spain, 28046

HUVA, Hospital Clínico Universitario Virgen De La Arrixaca

Murcia, Spain, 30120

Hospital Universitario y Politecnico La Fe

Valencia, Spain, 46026

Hospital Universitario Miguel Servet

Zaragoza, Spain, 50009

Sweden

Karolinska Institutet at Danderyd Hospital

Stockholm, Sweden, S-18288

Uppsala University

Uppsala, Sweden, SE-751 85

Switzerland

Cardiocentro

Lugano, Ticino, Switzerland, 6900

Taiwan

Mackay Memorial Hospital

Taipei City, Taiwan, 10449

Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, Meung, Thailand, 50200

Ramathibodi Hospital

Bangkok, Thailand, 10400

United Kingdom

Belfast Trust

Belfast, Antrim, United Kingdom, BT12 6BA

Bedford Hospital NHS Trust

Bedford, Bedfordshire, United Kingdom, MK42 9DJ

Luton and Dunstable University Hospital NHS FT

Luton, Berdfordshire, United Kingdom, LU4 0DZ

Papworth Hospital

Cambridge, Cambridgeshire, United Kingdom, CB23 3RE

Peterborough City Hospital

Peterborough, Cambs, United Kingdom, PE3 9GZ

The James Cook University Hospital, Middlesbrough

Middlesbrough, Cleveland, United Kingdom, TS4 3BW

Royal Bournemouth Hospital

Bournemouth, Dorset, United Kingdom, BH7 7DW

Dorset County Hospital

Dorchester, Dorset, United Kingdom, DT1 2JY

The University of Hull/Castle Hill Hospital

Cottingham, East Yorkshire, United Kingdom, HU16 5JQ

Broomfield Hospital

Chelmsford, Essex, United Kingdom, CM1 7ET

Southend University Hospital

Westcliff-on-Sea, Essex, United Kingdom, SS0 0RY

Hampshire Hospitals NHS Foundation Trust

Basingstoke, Hampshire, United Kingdom, RG24 9NA

Blackpool Teaching Hospitals

Blackpool, Lancashire, United Kingdom, FY3 8NR

The Pennine Acute Hospitals NHS Trust

Oldham, Lancashire, United Kingdom, OL1 2JH

Northwick Park Hospital Harrow/ Royal Brompton Hospital London

Harrow, Middlesex, United Kingdom, HA1 3UJ

South Eastern Health and Social Care

Belfast, Northern Ireland, United Kingdom, BT16 1RH

Cardiovascular Research Unit, Craigavon Area Hospital

Craigavon, Northern Ireland, United Kingdom, BT63 5QQ

Nottingham University Hospitals

Nottingham, Notts, United Kingdom, NG5 1PB

Royal Infirmary of Edinburgh

Edinburgh, Scotland, United Kingdom, EH4 2XU

University of Glasgow

Clydebank, Strathclyde, United Kingdom, G81 4DY

Russells Hall Hospital

Dudley, West Midlands, United Kingdom, DY1 2HQ

Bradford Royal Infirmary

Bradford, West Yorkshire, United Kingdom, BD9 6RJ

Pinderfields Hospital

Wakefield, West Yorkshire, United Kingdom, WF1 4DG

University College London Hospitals NHS Foundation Trust/Barts Health NHS Trust

London, United Kingdom, EC1A 7BE

Royal Free London NHS Foundation Trust

London, United Kingdom, NW3 2QG

King's College NHS Foundation Hospital

London, United Kingdom, SE13 6LH

Imperial College Healthcare NHS Trust

London, United Kingdom, W12OHS

Central Manchester University Hospital

Manchester, United Kingdom, M13 9WL

Sponsors and Collaborators

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

Investigators

• Study Chair: Judith S Hochman, MD; New York University
• Principal Investigator: David J Maron, MD; Stanford University

  Study Documents (Full-Text)

Documents provided by NYU Langone Health:

Study Protocol: Study Protocol v.1.0  [PDF] January 18, 2012

Study Protocol: Study Protocol v.2.0  [PDF] January 6, 2014

Study Protocol: Protocol Addendum  [PDF] September 22, 2016

Statistical Analysis Plan  [PDF] August 14, 2018

More Information

Additional Information:

Main Website for ISCHEMIA Trial 

Angioplasty 

Coronary Artery Bypass Surgery 

Coronary Artery Disease 

Heart Diseases 

ISCHEMIA Trial Update 

Publications:

Maron DJ, Stone GW, Berman DS, Mancini GB, Scott TA, Byrne DW, Harrell FE Jr, Shaw LJ, Hachamovitch R, Boden WE, Weintraub WS, Spertus JA. Is cardiac catheterization necessary before initial management of patients with stable ischemic heart disease? Results from a Web-based survey of cardiologists. Am Heart J. 2011 Dec;162(6):1034-1043.e13. doi: 10.1016/j.ahj.2011.09.001.

Phillips LM, Hachamovitch R, Berman DS, Iskandrian AE, Min JK, Picard MH, Kwong RY, Friedrich MG, Scherrer-Crosbie M, Hayes SW, Sharir T, Gosselin G, Mazzanti M, Senior R, Beanlands R, Smanio P, Goyal A, Al-Mallah M, Reynolds H, Stone GW, Maron DJ, Shaw LJ. Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA. J Nucl Cardiol. 2013 Dec;20(6):969-75. doi: 10.1007/s12350-013-9773-4.

ISCHEMIA Trial Research Group; Maron DJ, Hochman JS, O'Brien SM, Reynolds HR, Boden WE, Stone GW, Bangalore S, Spertus JA, Mark DB, Alexander KP, Shaw L, Berger JS, Ferguson TB Jr, Williams DO, Harrington RA, Rosenberg Y. International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial: Rationale and design. Am Heart J. 2018 Jul;201:124-135. doi: 10.1016/j.ahj.2018.04.011. Epub 2018 Apr 21.

Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Alexander KP, Senior R, Boden WE, Stone GW, Goodman SG, Lopes RD, Lopez-Sendon J, White HD, Maggioni AP, Shaw LJ, Min JK, Picard MH, Berman DS, Chaitman BR, Mark DB, Spertus JA, Cyr DD, Bhargava B, Ruzyllo W, Wander GS, Chernyavskiy AM, Rosenberg YD, Maron DJ; ISCHEMIA Research Group. Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial. JAMA Cardiol. 2019 Mar 1;4(3):273-286. doi: 10.1001/jamacardio.2019.0014. Erratum In: JAMA Cardiol. 2019 May 1;4(5):497.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Reynolds HR, Diaz A, Cyr DD, Shaw LJ, Mancini GBJ, Leipsic J, Budoff MJ, Min JK, Hague CJ, Berman DS, Chaitman BR, Picard MH, Hayes SW, Scherrer-Crosbie M, Kwong RY, Lopes RD, Senior R, Dwivedi SK, Miller TD, Chow BJW, de Silva R, Stone GW, Boden WE, Bangalore S, O'Brien SM, Hochman JS, Maron DJ; ISCHEMIA Research Group. Ischemia With Nonobstructive Coronary Arteries: Insights From the ISCHEMIA Trial. JACC Cardiovasc Imaging. 2023 Jan;16(1):63-74. doi: 10.1016/j.jcmg.2022.06.015. Epub 2022 Sep 14.

Garcia RA, Spertus JA, Benton MC, Jones PG, Mark DB, Newman JD, Bangalore S, Boden WE, Stone GW, Reynolds HR, Hochman JS, Maron DJ; ISCHEMIA Research Group. Association of Medication Adherence With Health Outcomes in the ISCHEMIA Trial. J Am Coll Cardiol. 2022 Aug 23;80(8):755-765. doi: 10.1016/j.jacc.2022.05.045.

Bangalore S, Spertus JA, Stevens SR, Jones PG, Mancini GBJ, Leipsic J, Reynolds HR, Budoff MJ, Hague CJ, Min JK, Boden WE, O'Brien SM, Harrington RA, Berger JS, Senior R, Peteiro J, Pandit N, Bershtein L, de Belder MA, Szwed H, Doerr R, Monti L, Alfakih K, Hochman JS, Maron DJ; ISCHEMIA Research Group. Outcomes With Intermediate Left Main Disease: Analysis From the ISCHEMIA Trial. Circ Cardiovasc Interv. 2022 Apr;15(4):e010925. doi: 10.1161/CIRCINTERVENTIONS.121.010925. Epub 2022 Apr 12.

Mark DB, Spertus JA, Bigelow R, Anderson S, Daniels MR, Anstrom KJ, Baloch KN, Cohen DJ, Held C, Goodman SG, Bangalore S, Cyr D, Reynolds HR, Alexander KP, Rosenberg Y, Stone GW, Maron DJ, Hochman JS; ISCHEMIA Research Group. Comprehensive Quality-of-Life Outcomes With Invasive Versus Conservative Management of Chronic Coronary Disease in ISCHEMIA. Circulation. 2022 Apr 26;145(17):1294-1307. doi: 10.1161/CIRCULATIONAHA.121.057363. Epub 2022 Mar 9.

Senior R, Reynolds HR, Min JK, Berman DS, Picard MH, Chaitman BR, Shaw LJ, Page CB, Govindan SC, Lopez-Sendon J, Peteiro J, Wander GS, Drozdz J, Marin-Neto J, Selvanayagam JB, Newman JD, Thuaire C, Christopher J, Jang JJ, Kwong RY, Bangalore S, Stone GW, O'Brien SM, Boden WE, Maron DJ, Hochman JS; ISCHEMIA Research Group. Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial. J Am Coll Cardiol. 2022 Feb 22;79(7):651-661. doi: 10.1016/j.jacc.2021.11.052.

Newman JD, Anthopolos R, Mancini GBJ, Bangalore S, Reynolds HR, Kunichoff DF, Senior R, Peteiro J, Bhargava B, Garg P, Escobedo J, Doerr R, Mazurek T, Gonzalez-Juanatey J, Gajos G, Briguori C, Cheng H, Vertes A, Mahajan S, Guzman LA, Keltai M, Maggioni AP, Stone GW, Berger JS, Rosenberg YD, Boden WE, Chaitman BR, Fleg JL, Hochman JS, Maron DJ. Outcomes of Participants With Diabetes in the ISCHEMIA Trials. Circulation. 2021 Oct 26;144(17):1380-1395. doi: 10.1161/CIRCULATIONAHA.121.054439. Epub 2021 Sep 15.

Lopez-Sendon JL, Cyr DD, Mark DB, Bangalore S, Huang Z, White HD, Alexander KP, Li J, Nair RG, Demkow M, Peteiro J, Wander GS, Demchenko EA, Gamma R, Gadkari M, Poh KK, Nageh T, Stone PH, Keltai M, Sidhu M, Newman JD, Boden WE, Reynolds HR, Chaitman BR, Hochman JS, Maron DJ, O'Brien SM. Effects of initial invasive vs. initial conservative treatment strategies on recurrent and total cardiovascular events in the ISCHEMIA trial. Eur Heart J. 2022 Jan 13;43(2):148-149. doi: 10.1093/eurheartj/ehab509.

Reynolds HR, Shaw LJ, Min JK, Page CB, Berman DS, Chaitman BR, Picard MH, Kwong RY, O'Brien SM, Huang Z, Mark DB, Nath RK, Dwivedi SK, Smanio PEP, Stone PH, Held C, Keltai M, Bangalore S, Newman JD, Spertus JA, Stone GW, Maron DJ, Hochman JS. Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity. Circulation. 2021 Sep 28;144(13):1024-1038. doi: 10.1161/CIRCULATIONAHA.120.049755. Epub 2021 Sep 9. Erratum In: Circulation. 2022 Jun 7;145(23):e1072. Circulation. 2022 Jul 5;146(1):e3.

White HD, O'Brien SM, Alexander KP, Boden WE, Bangalore S, Li J, Manjunath CN, Lopez-Sendon JL, Peteiro J, Gosselin G, Berger JS, Maggioni AP, Reynolds HR, Hochman JS, Maron DJ. Comparison of Days Alive Out of Hospital With Initial Invasive vs Conservative Management: A Prespecified Analysis of the ISCHEMIA Trial. JAMA Cardiol. 2021 Sep 1;6(9):1023-1031. doi: 10.1001/jamacardio.2021.1651.

Chaitman BR, Alexander KP, Cyr DD, Berger JS, Reynolds HR, Bangalore S, Boden WE, Lopes RD, Demkow M, Piero Perna G, Riezebos RK, McFalls EO, Banerjee S, Bagai A, Gosselin G, O'Brien SM, Rockhold FW, Waters DD, Thygesen KA, Stone GW, White HD, Maron DJ, Hochman JS; ISCHEMIA Research Group. Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons. Circulation. 2021 Feb 23;143(8):790-804. doi: 10.1161/CIRCULATIONAHA.120.047987. Epub 2020 Dec 3.

Lopes RD, Alexander KP, Stevens SR, Reynolds HR, Stone GW, Pina IL, Rockhold FW, Elghamaz A, Lopez-Sendon JL, Farsky PS, Chernyavskiy AM, Diaz A, Phaneuf D, De Belder MA, Ma YT, Guzman LA, Khouri M, Sionis A, Hausenloy DJ, Doerr R, Selvanayagam JB, Maggioni AP, Hochman JS, Maron DJ. Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial. Circulation. 2020 Nov 3;142(18):1725-1735. doi: 10.1161/CIRCULATIONAHA.120.050304. Epub 2020 Aug 29. Erratum In: Circulation. 2020 Oct 13;142(15):e236.

Gala ABE, Curzen N. Is There Still a Place for Revascularisation in the Management of Stable Coronary Artery Disease Following the ISCHEMIA Trial? Heart Int. 2020 Aug 8;14(1):13-15. doi: 10.17925/HI.2020.14.1.13. eCollection 2020.

Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Boden WE, Chaitman BR, Senior R, Lopez-Sendon J, Alexander KP, Lopes RD, Shaw LJ, Berger JS, Newman JD, Sidhu MS, Goodman SG, Ruzyllo W, Gosselin G, Maggioni AP, White HD, Bhargava B, Min JK, Mancini GBJ, Berman DS, Picard MH, Kwong RY, Ali ZA, Mark DB, Spertus JA, Krishnan MN, Elghamaz A, Moorthy N, Hueb WA, Demkow M, Mavromatis K, Bockeria O, Peteiro J, Miller TD, Szwed H, Doerr R, Keltai M, Selvanayagam JB, Steg PG, Held C, Kohsaka S, Mavromichalis S, Kirby R, Jeffries NO, Harrell FE Jr, Rockhold FW, Broderick S, Ferguson TB Jr, Williams DO, Harrington RA, Stone GW, Rosenberg Y; ISCHEMIA Research Group. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med. 2020 Apr 9;382(15):1395-1407. doi: 10.1056/NEJMoa1915922. Epub 2020 Mar 30.

Spertus JA, Jones PG, Maron DJ, O'Brien SM, Reynolds HR, Rosenberg Y, Stone GW, Harrell FE Jr, Boden WE, Weintraub WS, Baloch K, Mavromatis K, Diaz A, Gosselin G, Newman JD, Mavromichalis S, Alexander KP, Cohen DJ, Bangalore S, Hochman JS, Mark DB; ISCHEMIA Research Group. Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease. N Engl J Med. 2020 Apr 9;382(15):1408-1419. doi: 10.1056/NEJMoa1916370. Epub 2020 Mar 30.

Reynolds HR, Shaw LJ, Min JK, Spertus JA, Chaitman BR, Berman DS, Picard MH, Kwong RY, Bairey-Merz CN, Cyr DD, Lopes RD, Lopez-Sendon JL, Held C, Szwed H, Senior R, Gosselin G, Nair RG, Elghamaz A, Bockeria O, Chen J, Chernyavskiy AM, Bhargava B, Newman JD, Hinic SB, Jaroch J, Hoye A, Berger J, Boden WE, O'Brien SM, Maron DJ, Hochman JS; ISCHEMIA Research Group. Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia: Secondary Analysis of the ISCHEMIA Randomized Clinical Trial. JAMA Cardiol. 2020 Jul 1;5(7):773-786. doi: 10.1001/jamacardio.2020.0822. Erratum In: JAMA Cardiol. 2021 Aug 1;6(8):980.

Azevedo DFC, Lima EG, Ribeiro MOL, Linhares Filho JPP, Serrano Junior CV. Critical analysis of the classic indications for myocardial revascularization. Rev Assoc Med Bras (1992). 2019 Mar;65(3):319-325. doi: 10.1590/1806-9282.65.3.319. Epub 2019 Apr 11.

Shaw LJ, Xie JX, Phillips LM, Goyal A, Reynolds HR, Berman DS, Picard MH, Bhargava B, Devlin G, Chaitman BR. Optimising diagnostic accuracy with the exercise ECG: opportunities for women and men with stable ischaemic heart disease. Heart Asia. 2016 Jun 1;8(2):1-7. doi: 10.1136/heartasia-2016-010736. eCollection 2016.

Kataoka A, Scherrer-Crosbie M, Senior R, Gosselin G, Phaneuf D, Guzman G, Perna G, Lara A, Kedev S, Mortara A, El-Hajjar M, Shaw LJ, Reynolds HR, Picard MH. The value of core lab stress echocardiography interpretations: observations from the ISCHEMIA Trial. Cardiovasc Ultrasound. 2015 Dec 18;13:47. doi: 10.1186/s12947-015-0043-2.

Stone GW, Hochman JS, Williams DO, Boden WE, Ferguson TB Jr, Harrington RA, Maron DJ. Medical Therapy With Versus Without Revascularization in Stable Patients With Moderate and Severe Ischemia: The Case for Community Equipoise. J Am Coll Cardiol. 2016 Jan 5;67(1):81-99. doi: 10.1016/j.jacc.2015.09.056. Epub 2015 Nov 23.

Wasilewski J, Polonski L, Lekston A, Osadnik T, Regula R, Bujak K, Kurek A. Who is eligible for randomized trials? A comparison between the exclusion criteria defined by the ISCHEMIA trial and 3102 real-world patients with stable coronary artery disease undergoing stent implantation in a single cardiology center. Trials. 2015 Sep 15;16:411. doi: 10.1186/s13063-015-0934-4.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT01471522
• Other Study ID Numbers: 11-00498; 1U01HL105907 ( U.S. NIH Grant/Contract )
• First Posted: November 15, 2011
• Results First Posted: July 23, 2020
• Last Update Posted: June 1, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data will be submitted to the NHLBI according to their guidelines within 3 years after the final patient follow-up (June 30, 2019) or 2 years after the main paper of the trial has been published, whichever comes first.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: June 2022

Additional relevant MeSH terms:

Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes