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

• Sponsor: NYU Langone Health (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01471522
• Collaborator: New York University (Other), Stanford University (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), Albany Stratton VA Medical Center (U.S. Fed), Cedars-Sinai Medical Center (Other), Columbia University (Other), Duke University (Other), East Carolina University (Other), Emory University (Other), Harvard University (Other), Massachusetts General Hospital (Other), Montreal Heart Institute (Other), University of British Columbia (Other), University of Missouri, Kansas City (Other), Vanderbilt University (Other)
• Enrollment: 5,179
• Locations: 320
• Arms: 2
• Duration (Months): 130.9
• Patients Per Site: 16.2
• Patients Per Site Per Month: 0.1

Study Details

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

1. 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.

2. 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	N/A

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
• 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: Jul 1, 2012
• Actual Primary Completion Date: Jun 30, 2019
• Anticipated 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 Names: 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 Names: 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 Names: PCI ; Behavioral: Lifestyle; diet, physical activity, smoking cessation; Other Names: Behavior change ; Drug: Medication; antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies; Other Names: 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 Names: Behavior change ; Drug: Medication; antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies; Other Names: 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 [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) [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 [5 years]

4. Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction [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 [5 years]

6. Cumulative Event Rate of Death From Any Cause [5 years]

7. Number of Participants That Experienced Myocardial Infarction [5 years]

8. Cumulative Event Rate of Myocardial Infarction [5 years]

9. Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative [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 [5 years]

11. Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative [5 years]

12. Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	UAB Vascular Biology and Hypertension Program	Birmingham	Alabama	United States	35294
2	Yuma Regional Medical Center	Yuma	Arizona	United States	85364
3	Cedars Sinai Medical Center	Beverly Hills	California	United States	90211
4	UCSF - Fresno Community Regional Medical Center	Fresno	California	United States	93721
5	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
6	University of California Irvine Medical Center	Orange	California	United States	92868
7	Palo Alto Medical Foundation Research Institute	Palo Alto	California	United States	94087
8	VA Palo Alto HealthCare System	Palo Alto	California	United States	94550
9	Kaiser Permanente San Jose	San Jose	California	United States	94538
10	Coastal Heart Medical Group	Santa Ana	California	United States	92704
11	Stanford University School of Medicine	Stanford	California	United States	94305
12	Torrance Memorial Medical Center	Torrance	California	United States	90505
13	South Denver Cardiology Associates, P.C.	Littleton	Colorado	United States	80120
14	Medical Center of the Rockies	Loveland	Colorado	United States	80538
15	VA Connecticut Healthcare System	West Haven	Connecticut	United States	06111
16	Daytona Heart Group	Daytona Beach	Florida	United States	32114
17	Malcom Randall VAMC	Gainesville	Florida	United States	32608
18	Mayo Clinic Florida	Jacksonville	Florida	United States	32224
19	Cardiovascular Center of Sarasota	Sarasota	Florida	United States	34239
20	Sarasota Memorial Hospital	Sarasota	Florida	United States	34239
21	University of South Florida	Tampa	Florida	United States	33606
22	Emory University	Atlanta	Georgia	United States	30322
23	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
24	Advanced Heart Care Group	Fairview Heights	Illinois	United States	62208
25	Loyola University Medical Center	Maywood	Illinois	United States	60153
26	Indiana University/Krannert Institute of Cardiology	Indianapolis	Indiana	United States	46202
27	Midwest Cardiovascular Research Foundation	Davenport	Iowa	United States	52803
28	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
29	University of Kentucky	Lexington	Kentucky	United States	40536
30	Lexington VA Medical Center	Lexington	Kentucky	United States	42503
31	University of Louisville	Louisville	Kentucky	United States	40292
32	Cardiovascular Specialists of Southwest Louisiana	Lake Charles	Louisiana	United States	70601
33	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
34	NIH Heart Center at Suburban Hospital	Bethesda	Maryland	United States	20814
35	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889
36	Brigham & Women's Hospital, Harvard Medical School	Boston	Massachusetts	United States	02115
37	Boston Medical Center	Boston	Massachusetts	United States	02118
38	VA Boston Healthcare System	West Roxbury	Massachusetts	United States	02132
39	Saint Vincent Hospital at Worcester Medical Center	Worcester	Massachusetts	United States	01608
40	Henry Ford Health System	Detroit	Michigan	United States	48202
41	Spectrum Health	Grand Rapids	Michigan	United States	49503
42	Covenant Medical Center, Inc.	Saginaw	Michigan	United States	01876
43	Providence - Providence Park Hospital	Southfield	Michigan	United States	48075
44	Michigan Heart, PC	Ypsilanti	Michigan	United States	48197
45	Minneapolis VAMC	Minneapolis	Minnesota	United States	55417
46	University of Minnesota	Minneapolis	Minnesota	United States	55455
47	Mayo Clinic	Rochester	Minnesota	United States	55905
48	HealthEast Saint Joseph's Hospital	Saint Paul	Minnesota	United States	55102
49	Saint Luke's Hospital	Kansas City	Missouri	United States	64111
50	Kansas City VA Medical Center	Kansas City	Missouri	United States	64128
51	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
52	AtlantiCare Regional Medical Center	Pomona	New Jersey	United States	08240
53	Hackensack University Medical Center	Saddle Brook	New Jersey	United States	07663
54	Albany Medical Center Hospital	Albany	New York	United States	12208
55	Samuel Stratton VA Medical Center of Albany NY	Albany	New York	United States	12208
56	Capital Cardiology Associates	Albany	New York	United States	12211
57	NYU-HHC Lincoln Medical and Mental Health Center	Bronx	New York	United States	10451
58	Jacobi Medical Center	Bronx	New York	United States	10461
59	NYU-HHC Kings County Hospital Center	Brooklyn	New York	United States	11203
60	New York -Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York	United States	11215
61	NYU-HHC Woodhull Hospital	Brooklyn	New York	United States	11229
62	Coney Island Hospital	Brooklyn	New York	United States	11235
63	NYP Medical Medical Group Hudson Valley Cardiology	Cortlandt Manor	New York	United States	10567
64	New York University - Langone Cardiovascular Associates	Flushing	New York	United States	11355
65	Mid Valley Cardiology	Kingston	New York	United States	12401
66	Northwell Health - Manhasset	Manhasset	New York	United States	11030
67	NYU Winthrop	Mineola	New York	United States	11501
68	VA New York Harbor Health Care System	New York	New York	United States	10010
69	Beth Israel Medical Center	New York	New York	United States	10016
70	NYU Langone Medical Center-Bellevue Hospital	New York	New York	United States	10016
71	NYU New York Medical Associates	New York	New York	United States	10022
72	Mount Sinai Saint Luke's Hospital	New York	New York	United States	10025
73	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
74	Columbia University Medical Center	New York	New York	United States	10032
75	University of Rochester	Rochester	New York	United States	14642
76	Cardiology Associates of Schenectady P.C.	Schenectady	New York	United States	12309
77	Asheville Cardiology Associates	Asheville	North Carolina	United States	28803
78	Duke University Medical Center	Durham	North Carolina	United States	27710
79	Sanford Health	Fargo	North Dakota	United States	58122
80	Cincinnati VA Medical Center	Cincinnati	Ohio	United States	45220
81	Louis Stokes Cleveland Veterans Affairs Medical Center	Cleveland	Ohio	United States	44106
82	Ohio Health Grant Medical Center	Columbus	Ohio	United States	43215
83	Oklahoma Heart Institute	Tulsa	Oklahoma	United States	74133
84	Oregon Health & Science University	Portland	Oregon	United States	97201
85	Providence Heart and Vascular Institute	Portland	Oregon	United States	97225
86	Saint Luke's Hospital and Health Network	Bethlehem	Pennsylvania	United States	18018
87	Holy Spirit Hospital Cardiovascular Institute	Camp Hill	Pennsylvania	United States	17011
88	Doylestown Health Cardiology	Doylestown	Pennsylvania	United States	18901
89	Conemaugh Valley Memorial Hospital	Johnstown	Pennsylvania	United States	15905
90	Miriam Hospital	Providence	Rhode Island	United States	02906
91	Kent Hospital	Warwick	Rhode Island	United States	02886
92	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
93	Saint Thomas Hospital	Nashville	Tennessee	United States	373203
94	V.A. North Texas Health Care System	Dallas	Texas	United States	75216
95	Baylor College of Medicine	Houston	Texas	United States	77030
96	Baylor St. Luke's Medical Center	Houston	Texas	United States	77030
97	Houston Heart & Vascular Associates	Houston	Texas	United States	77339
98	Baylor Research Institute at Legacy Heart Center	Plano	Texas	United States	75024
99	The Heart Hospital Baylor	Plano	Texas	United States	75093
100	Audie Murphy V.A.	San Antonio	Texas	United States	78229
101	Medicus Alliance Clinical Research Org., Inc.	Sugar Land	Texas	United States	77478
102	Wichita Falls Heart Clinic	Wichita Falls	Texas	United States	76301
103	Salt Lake City VA Medical Center	Salt Lake City	Utah	United States	84148
104	VAMC-White River Junction	White River Junction	Vermont	United States	05009
105	Cardiovascular Associates, Ltd.	Chesapeake	Virginia	United States	23320
106	Stroobants Cardiovascular Center	Lynchburg	Virginia	United States	24501
107	Winchester Cardiology and Vascular Medicine, PC	Winchester	Virginia	United States	22601
108	University of Washington Medical Center	Bellevue	Washington	United States	98004
109	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
110	Hospital Italiano Regional del Sur Bahia Blanca	Bahia Blanca	Buenos Aires	Argentina	8000
111	Fundacion Favaloro	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1093AAS
112	Instituto Medico DAMIC	Cordoba	CBA	Argentina	5009
113	Clinica Del Prado	Cordoba		Argentina	5000
114	Clinica Romagosa and Clinica De La Familia	Cordoba		Argentina	5000
115	Clínica Privada Vélez Sarsfield	Cordoba		Argentina	5000
116	John Hunter Hospital	New Lambton Heights	New South Wales	Australia	2305
117	Flinders Medical Centre	Adelaide	South Australia	Australia	5042
118	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
119	Royal Perth Hospital	Perth	Western Australia	Australia	6000
120	LKH Graz West Austria	Graz	Stmk	Austria	8020
121	Medical University of Vienna, Department of Cardiology	Vienna	Wien	Austria	1090
122	Wilhelminen Hospital Vienna	Vienna	Wien	Austria	A-1160
123	University Hospital Leuven	Leuven	Brabant	Belgium	3000
124	Fundacao Bahiana de Cardilogia	Salvador	Bahia	Brazil	41810-010
125	Hospital Lifecenter	Belo Horizonte	Minas Gerais	Brazil	30110-921
126	Hospital Maternidade e Pronto Socorro Santa Lucia	Pocos de Caldas	Minas Gerais	Brazil	37701-045
127	Quanta Diagnostico & Terapia	Curitiba	Parana	Brazil	80045-170
128	Hospital Cardiologico Costantini	Curitiba	Parana	Brazil	80320-320
129	Hospital Pró-Cardíaco	Botafogo	Rio De Janeiro	Brazil	22280-020
130	Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sol	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
131	Instituto de Cardiologia de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90620-001
132	Hospital Sao Vicente de Paulo	Fundo	RS	Brazil	99010080
133	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS	Brazil	90035-903
134	Instituto Dante Pazzanese de Cardiologia	Ibirapuera	Sao Paulo	Brazil	04012-909
135	Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirao Preto	Sao Paulo	Brazil	14048-900
136	Hospital TotalCor	Sao Paulo	SP	Brazil	1418100
137	Hospital da Bahia	Salvador		Brazil	BA, 41820-011
138	Unifesp - Hospital Sao Paulo	Sao Paulo		Brazil	04025-011
139	Heart Institute (InCor) University of São Paulo	Sao Paulo		Brazil	05403-000
140	Hospital Celso Pierro	Sao Paulo		Brazil	13059-740
141	University of Calgary	Calgary	Alberta	Canada	T2N 2T9
142	University of Alberta	Edmonton	Alberta	Canada	T6G 2B7
143	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
144	West Lincoln Memorial Hospital	Grimsby	Ontario	Canada	L3M 1P3
145	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L 2X2
146	London Health Sciences Centre	London	Ontario	Canada	N6A 5A5
147	Dixie Medical Group	Mississauga	Ontario	Canada	L4W 0C2
148	Dr. James Cha	Oshawa	Ontario	Canada	L1J 2K1
149	Scarborough Cardiology Research	Scarborough	Ontario	Canada	M1E 5E9
150	Saint Catharines General Hospital	St. Catharines	Ontario	Canada	L2S0A9
151	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
152	Women's College Hospital	Toronto	Ontario	Canada	M5G 1N8
153	University Health Network	Toronto	Ontario	Canada	M5G 2C4
154	Northwest GTA Cardiovascular and Heart Rhythm Program	Vaughan	Ontario	Canada	L4H0P6
155	Montreal Heart Institute	Montreal	Quebec	Canada	H1T 1C8
156	Centre Intégré Universitaire de Santé et de Services Sociaux du Montréal	Montréal	Quebec	Canada	H4J 1C5
157	CISSSL - Hopital Pierre-Le Gardeur	Terrebonne	Quebec	Canada	J6V 2H2
158	Centre Hospitalier de Regional Trois-Rivieres	Trois-Rivieres	Quebec	Canada	G8Z 3R9
159	University of Ottawa Heart Institute	Ottawa		Canada	K1Y 4W7
160	Beijing Chao-yang Hospital, Capital Medical University	Beijing	Beijing	China	100020
161	Chinese Academy of Medical Sciences, Fuwai Hospital	Beijing	Beijing	China	100037
162	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
163	Beijing Anzhen Hospital	Beijing	Chaoyang	China	100029
164	Liangxiang Hospital, Beijing Fangshan District	Beijing	Fangshan	China	102401
165	Guangdong General Hospital	Guangzhou	Guangdong	China	510100
166	Tangshan Gongren Hospital	Tangshan	Hebei	China	063000
167	The Second Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450014
168	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450052
169	Tongji Medical College	Wuhan	Hubei	China	430030
170	Wuhan Asia Heart Hospital	Wuhan	Hubei	China
171	Wuhan Union Hospital, Tongji Medical College, Huazhong Science and Tech University	Wuhan	Hubei	China
172	Affiliated Zhongshan Hospital of Dalian University	Dalian	Liaoning	China	116001
173	Affiliated Hospital of Jining Medical University	Jining	Shandong	China	272000
174	Qingdao Fuwai Hospital	Qingdao	Shandong	China	266071
175	Shanxi Cardiovascular Hospital	Taiyuan	Shanxi	China	030024
176	Shanxi Provincial People's Hospital	Xian	Shanxi	China	710000
177	TEDA International Cardiovascular Hospital	Tianjing	Tianjing	China	300457
178	First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang	China	830054
179	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310009
180	Cairo University	Cairo		Egypt	11562
181	C.H. Louis Pasteur	Chatres	Centre	France	28018
182	Ambroise Pare Hospital	Boulogne	Ile De France	France	92100
183	Centre Hospitalier Sud Francilien	Corbeil-Essonnes cedex	Ile De France	France	91100
184	Antoine-Beclere Hospital	Clamart Cedex	Ile-de-France	France	92141
185	Bichat Hospital	Paris	Ile-de-France	France	75018
186	Grenoble University Hospital	Grenoble	Isere	France	38700
187	Centre Hospitalier Universitaire d'Angers	Angers Cedex 9	Pays De La Loire	France	49933
188	Robert-Bosch-Krankenhaus	Stuttgart	BW	Germany	70376
189	Universitatsklinikum Bonn	Bonn	NRW	Germany	53105
190	Praxisklinik Herz Und Gefaesse	Dresden	Saxony	Germany	D-01099
191	University Hospital Jena	Jena	Thuringia	Germany	07747
192	University of Szeged	Szeged	Szeged Megyei Varos	Hungary	6720
193	Eszszk- Szent Istvan Hospital	Budapest		Hungary	1097
194	Military Hospital, Budapest	Budapest		Hungary	1117
195	Heart and Vascular Center, Semmelweis University	Budapest		Hungary	1122
196	George Gottsegen National Institute of Cardiology	Budapest		Hungary	H-1096
197	CARE Hospital	Hyderabad	Andhra Pradesh	India	500034
198	Gurunanak CARE Hospital	Hyderabad	AP	India	500020
199	Dr Ram Manohar Lohia Hospital	New Delhi	Delhi	India	110001
200	Fortis Escort Heart Institute	New Delhi	Delhi	India	110025
201	Batra Hospital and Medical Research Centre (BHMRC)	New Delhi	Delhi	India	110062
202	Fortis Healthcare Fl.t Lt. Rajan Dhall Hospital	New Delhi	Delhi	India	110070
203	Sri Jayadeva Institute of Cardiovascular Sciences and Research	Bangalore	Karnataka	India	560069
204	Government Medical College	Calicut	Kerala	India	673008
205	MOSC Medical College Hospital, Kolenchery	Kolenchery	Kerala	India	682311
206	Sree Chitra Tirunal Institute for Medical Sciences and Technology	Trivandrum	Kerala	India	695011
207	Ruby Hall Clinic,Grant Medical Foundation	Pune	Maharashtra	India	411001
208	KEM Hospital Pune	Pune	Maharashtra	India	411011
209	Hero DMC Heart Institute, Dayanand Medical College and Hospital	Ludhiana	Punjab	India	141001
210	Apollo Research and Innovation	Chennai	Tamil Nadu	India	600081
211	Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER)	Pondicherry	Tamil Nadu	India	605006
212	CARE Nampally	Hyderabad	Telangana	India	500001
213	Apollo Research & Innovations	Hyderabad	Telangana	India	600081
214	King George's Medical University, Department of Cardiology	Lucknow	Uttar Pradesh	India	226003
215	All India Institute of Medical Sciences	New Delhi		India	110029
216	Rambam Medical Center	Haifa		Israel	31096
217	Assuta Medical Centers	Tel-Aviv		Israel	67891
218	AORN Dei Colli "V. Monaldi" UOC Cardiologia Università della Campania "L.Vanvitelli"	Napoli	Campania	Italy	80131
219	Ospedale "G.B. Morgagni - L. Pierantoni" Forli (AUSL della Romagna)	Forli	Emilia-Romagna	Italy	47100
220	IRCCS "Casa Sollievo della Sofferenza"	San Giovanni Rotondo	FG	Italy	71013
221	Cardiology and CCU - Ospedali Riuniti Ancona	Ancona	Marche	Italy	60020
222	Policlinico di Monza, Monza MB	Monza	MB	Italy	20900
223	Humanitas Research Hospital, Rozzano (MI)	Rozzano	Milano	Italy	20089
224	Azienda Ospedaliera S. Croce e Carle	Cuneo	Piemonte	Italy	12100
225	UO Cardiologia Ospedale SS Cosma e Damiano	Pescia	Tuscany	Italy	54100
226	Azienda Servizi Sanitaria n.3 Alto Friuli-Collinare-Medio Friuli	Tolmezzo	Udine	Italy	33028
227	University of Padua- Cardiology Clinic	Padua	Veneto	Italy	35100
228	Ospedale Regionale Umberto Parini	Aosta		Italy	11100
229	Clinica Mediterranea	Naples		Italy	80121
230	Ospedale di Circolo e Fondazione Macchi	Varese		Italy	21100
231	National Cerebral and Cardiovascular Center	Suita-shi	Osaka	Japan	565-8565
232	Saitama Medical University	Hidaka	Saitama	Japan	350-0495
233	Keio University Hospital	Shinjuku-Ku	Tokyo	Japan	160-8582
234	Vilnius University Hospital Santariskes Clinic	Vilnius		Lithuania	LT-08661
235	Institut Jantung Negara	Kuala Lumpur	Wilayah Persekutuan	Malaysia	50400
236	Instituto Mexicano del Seguro Social	Benito Juarez	DF	Mexico	3100
237	Instituto Nacional de Cardiología "Ignacio Chávez"	Mexico City	Distrito Federal	Mexico	14080
238	Cardio Research Hartcentrum OLVG	Amsterdam	NH	Netherlands	1091 AC
239	Radboudumc	Nijmegen		Netherlands	6500 HB
240	Isala Klinieken	Zwolle		Netherlands	8025 AB
241	Waikato Hospital	Hamilton	Waikato	New Zealand	3240
242	Auckland City Hospital	Auckland		New Zealand	1142
243	University Clinic of Cardiology	Skopje	Republic Of Macedo	North Macedonia	1000
244	Instituto Neuro Cardiovascular De Las Americas	Miraflores	Lima	Peru	18
245	T.Marciniak Hospital	Wrocław	Dolny Śląsk	Poland	54-090
246	Cardiology Clinic, Medical University in Lodz	Lodz	Lodzkie	Poland	91-425
247	Department of Coronary Disease, John Paul II Hospital, Jagiellonian University Medical College	Krakow	Maopolskie	Poland	31-200
248	Institute of Cardiology, Warsaw	Warsaw	Mazovian	Poland	04-628
249	Coronary and Structural Heart Diseases Department, Institute of Cardiology	Warsaw	Mazowieckie	Poland	04-628
250	Department of Interventional Cardiology & Angiology, Institute of Cardiology	Warsaw	Mazowieckie	Poland	04-628
251	Medical University of Warsaw	Warsaw	Mazowieckie	Poland	PL-02-097
252	Department of Internal Medicine and Cardiology, Infant Jesus Teaching Hospital, Medical University of Warsaw	Warszawa	Mazowieckie	Poland	02-005
253	University Hospital in Bialystok	Bialystok	Podlaskie	Poland	15-276
254	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
255	Szpital Kliniczny Przemienienia Pańskiego	Poznan		Poland	61-848
256	Military Hospital / Medical University	Wroclaw		Poland	50-981
257	Hospital de Santa Marta	Lisboa		Portugal	1150-291
258	Santa Maria University Hospital, Cardiology Department, CHLN	Lisbon		Portugal	1649-028
259	Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE	Vila Nova de Gaia		Portugal	4434-502
260	Emergency County Hospital Baia Mare	Baia Mare		Romania	021967
261	Emergency Institute of Cardiovascular Diseases ''Prof. Dr. C. C. Iliescu''	Bucharest		Romania	022328
262	National Medical Research Center for Cardiovascuar Surgery	Moscow	Gorod Moskva	Russian Federation	121552
263	E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation	Novosibirsk	Novosibirskaya Oblast	Russian Federation	630055
264	North-Western State Medical University	Saint Petersburg		Russian Federation	199106
265	Federal Almazov North-West Medical Research Centre	Saint-Petersburg		Russian Federation	197341
266	King AbdulAziz Cardiac Center	Riyadh	Central Province	Saudi Arabia	11426
267	Institute of Cardiovascular Diseases Vojvodina, Sremska Kamenica, Serbia and Faculty of Medicine, University of Novi Sad	Sremska Kamenica	Vojvodina	Serbia	21204
268	Clinical Center of Serbia	Belgrade		Serbia	11000
269	Faculty of Medicine, University of Belgrade; Cardiology Clinic, Clinical Center of Serbia	Belgrade		Serbia	11000
270	University Clinical Hospital Zvezdara	Belgrade		Serbia	11000
271	University Hospital Center Bezanijska Kosa	Belgrade		Serbia	11000
272	Clinical Center Kragujevac	Kragujevac		Serbia	11000
273	Clinic for Cardiovascular Diseases, Clinical Center Nis	Nis		Serbia	18000
274	National University Heart Center Singapore	Singapore		Singapore	119228
275	National Heart Centre Singapore	Singapore		Singapore	169609
276	Tan Tock Seng Hospital	Singapore		Singapore	308433
277	Groote Schuur Hospital / University of Cape Town	Cape Town	Western Cape	South Africa	7945
278	Hospital Clinico Universitario de Santiago	Santiago de Compostela	La Coruna	Spain	15706
279	Complexo Hospitalario Universitario A Coruña (CHUAC) Sergas, Department of Cardiology. INIBIC A Coruña. CIBER-CV. Universidad de A Coruña, Spain	A Coruna		Spain	15008
280	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025
281	Hospital De Bellvitge	Barcelona		Spain	08907
282	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
283	Hospital La Paz. IdiPaz	Madrid		Spain	28046
284	HUVA, Hospital Clínico Universitario Virgen De La Arrixaca	Murcia		Spain	30120
285	Hospital Universitario y Politecnico La Fe	Valencia		Spain	46026
286	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
287	Karolinska Institutet at Danderyd Hospital	Stockholm		Sweden	S-18288
288	Uppsala University	Uppsala		Sweden	SE-751 85
289	Cardiocentro	Lugano	Ticino	Switzerland	6900
290	Mackay Memorial Hospital	Taipei City		Taiwan	10449
291	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai	Meung	Thailand	50200
292	Ramathibodi Hospital	Bangkok		Thailand	10400
293	Belfast Trust	Belfast	Antrim	United Kingdom	BT12 6BA
294	Bedford Hospital NHS Trust	Bedford	Bedfordshire	United Kingdom	MK42 9DJ
295	Luton and Dunstable University Hospital NHS FT	Luton	Berdfordshire	United Kingdom	LU4 0DZ
296	Papworth Hospital	Cambridge	Cambridgeshire	United Kingdom	CB23 3RE
297	Peterborough City Hospital	Peterborough	Cambs	United Kingdom	PE3 9GZ
298	The James Cook University Hospital, Middlesbrough	Middlesbrough	Cleveland	United Kingdom	TS4 3BW
299	Royal Bournemouth Hospital	Bournemouth	Dorset	United Kingdom	BH7 7DW
300	Dorset County Hospital	Dorchester	Dorset	United Kingdom	DT1 2JY
301	The University of Hull/Castle Hill Hospital	Cottingham	East Yorkshire	United Kingdom	HU16 5JQ
302	Broomfield Hospital	Chelmsford	Essex	United Kingdom	CM1 7ET
303	Southend University Hospital	Westcliff-on-Sea	Essex	United Kingdom	SS0 0RY
304	Hampshire Hospitals NHS Foundation Trust	Basingstoke	Hampshire	United Kingdom	RG24 9NA
305	Blackpool Teaching Hospitals	Blackpool	Lancashire	United Kingdom	FY3 8NR
306	The Pennine Acute Hospitals NHS Trust	Oldham	Lancashire	United Kingdom	OL1 2JH
307	Northwick Park Hospital Harrow/ Royal Brompton Hospital London	Harrow	Middlesex	United Kingdom	HA1 3UJ
308	South Eastern Health and Social Care	Belfast	Northern Ireland	United Kingdom	BT16 1RH
309	Cardiovascular Research Unit, Craigavon Area Hospital	Craigavon	Northern Ireland	United Kingdom	BT63 5QQ
310	Nottingham University Hospitals	Nottingham	Notts	United Kingdom	NG5 1PB
311	Royal Infirmary of Edinburgh	Edinburgh	Scotland	United Kingdom	EH4 2XU
312	University of Glasgow	Clydebank	Strathclyde	United Kingdom	G81 4DY
313	Russells Hall Hospital	Dudley	West Midlands	United Kingdom	DY1 2HQ
314	Bradford Royal Infirmary	Bradford	West Yorkshire	United Kingdom	BD9 6RJ
315	Pinderfields Hospital	Wakefield	West Yorkshire	United Kingdom	WF1 4DG
316	University College London Hospitals NHS Foundation Trust/Barts Health NHS Trust	London		United Kingdom	EC1A 7BE
317	Royal Free London NHS Foundation Trust	London		United Kingdom	NW3 2QG
318	King's College NHS Foundation Hospital	London		United Kingdom	SE13 6LH
319	Imperial College Healthcare NHS Trust	London		United Kingdom	W12OHS
320	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)

• Study Protocol: Study Protocol v.1.0 - Jan 18, 2012
• Study Protocol: Study Protocol v.2.0 - Jan 6, 2014
• Study Protocol: Protocol Addendum - Sep 22, 2016
• Statistical Analysis Plan - Aug 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

• 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.
• 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. Review.
• 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. Review.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT01471522
• Other Study ID Numbers: 11-00498; 1U01HL105907
• First Posted: Nov 15, 2011
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Ischemia

Study Results

Participant Flow

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. Cardiac catheterization: Narrowed blood vessels can be opened without surgery using stents or bypassed with surgery. To determine the best approach, the doctor must assess the severity of blood vessel narrowings. This procedure is known as cardiac catheterization. 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, allowing more blood flow to the heart. Percutaneous coronary intervention: done as part of the cardiac catheterization 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.	Optimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms. Lifestyle: diet, physical activity, smoking cessation Medication: antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
Period Title: Overall Study
STARTED	2588	2591
COMPLETED	2524	2543
NOT COMPLETED	64	48

Baseline Characteristics

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy	Total
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy	Total of all reporting groups
Overall Participants	2588	2591	5179
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	64	64	64
Sex: Female, Male (Count of Participants)
Female	606 23.4%	562 21.7%	1168 22.6%
Male	1982 76.6%	2029 78.3%	4011 77.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	372 14.4%	391 15.1%	763 14.7%
Not Hispanic or Latino	2030 78.4%	2022 78%	4052 78.2%
Unknown or Not Reported	186 7.2%	178 6.9%	364 7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	8 0.3%	5 0.2%	13 0.3%
Asian	747 28.9%	738 28.5%	1485 28.7%
Native Hawaiian or Other Pacific Islander	5 0.2%	7 0.3%	12 0.2%
Black or African American	96 3.7%	108 4.2%	204 3.9%
White	1706 65.9%	1697 65.5%	3403 65.7%
More than one race	7 0.3%	5 0.2%	12 0.2%
Unknown or Not Reported	19 0.7%	31 1.2%	50 1%
Region of Enrollment (Count of Participants)
Africa	8 0.3%	5 0.2%	13 0.3%
Asia	791 30.6%	786 30.3%	1577 30.4%
Europe	853 33%	865 33.4%	1718 33.2%
Latin America	239 9.2%	239 9.2%	478 9.2%
Middle East	10 0.4%	10 0.4%	20 0.4%
North America	648 25%	652 25.2%	1300 25.1%
Pacifica	39 1.5%	34 1.3%	73 1.4%

Outcome Measures

1. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
Count of Participants [Participants]	318 12.3%	352 13.6%

2. Primary Outcome

Title	Cumulative Event Rate of Primary Composite Outcome (Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, Heart Failure, or Resuscitated Cardiac Arrest)
Description	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).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
At 6 months	5.3	3.4
At 1 year	7.0	5.4
At 2 years	9.0	9.5
At 3 years	11.3	12.7
At 4 years	13.3	15.5
At 5 years	16.4	18.2

3. Primary Outcome

Title	Number of Participants That Experienced Death From Cardiovascular Causes or Myocardial Infarction
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
Count of Participants [Participants]	276 10.7%	314 12.1%

4. Primary Outcome

Title	Cumulative Event Rate of Death From Cardiovascular Causes or Myocardial Infarction
Description	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).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
At 6 months	4.8	2.9
At 1 year	6.2	4.6
At 2 years	7.9	8.2
At 3 years	9.7	11.0
At 4 years	11.7	13.9
At 5 years	14.2	16.5

5. Primary Outcome

Title	Number of Participants That Experienced Death From Any Cause
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
Count of Participants [Participants]	145 5.6%	144 5.6%

6. Primary Outcome

Title	Cumulative Event Rate of Death From Any Cause
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
At 6 months	0.8	0.4
At 1 year	1.7	1.0
At 2 years	2.8	2.9
At 3 years	4.3	4.3
At 4 years	6.5	6.4
At 5 years	9.0	8.3

7. Primary Outcome

Title	Number of Participants That Experienced Myocardial Infarction
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
Count of Participants [Participants]	210 8.1%	233 9%

8. Primary Outcome

Title	Cumulative Event Rate of Myocardial Infarction
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Invasive Strategy (INV)	Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)	Conservative Strategy
Measure Participants	2588	2591
At 6 months	4.3	2.6
At 1 year	5.3	3.8
At 2 years	6.3	6.5
At 3 years	7.7	8.5
At 4 years	8.9	10.1
At 5 years	10.3	11.9

9. Primary Outcome

Title	Estimated Difference in Cumulative Event Rate ( %) of Primary Composite Outcome: Invasive Minus Conservative
Description	The primary composite outcome includes death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Invasive = 2588; Conservative = 2591

Arm/Group Title	Between Invasive and Conservative Strategy Arms
Arm/Group Description	Invasive vs. Conservative
Measure Participants	5179
At 6 months	1.9
At 1 year	1.5
At 2 years	-0.5
At 3 years	-1.3
At 4 years	-2.2
At 5 years	-1.8

10. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Invasive = 2588; Conservative = 2591

Arm/Group Title	Between Invasive and Conservative Strategy Arms
Arm/Group Description	Invasive vs. Conservative
Measure Participants	5179
At 6 months	1.9
At 1 year	1.6
At 2 years	-0.3
At 3 years	-1.3
At 4 years	-2.2
At 5 years	-2.3

11. Primary Outcome

Title	Estimated Difference in Cumulative Event Rate of Death From Any Cause: Invasive Minus Conservative
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Invasive = 2588; Conservative = 2591

Arm/Group Title	Between Invasive and Conservative Strategy Arms
Arm/Group Description	Invasive vs. Conservative
Measure Participants	5179
At 6 months	0.4
At 1 year	0.7
At 2 years	-0.1
At 3 years	0
At 4 years	0.1
At 5 years	0.7

12. Primary Outcome

Title	Estimated Difference in Cumulative Event Rate of Myocardial Infarction: Invasive Minus Conservative
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Invasive = 2588; Conservative = 2591

Arm/Group Title	Between Invasive and Conservative Strategy Arms
Arm/Group Description	Invasive vs. Conservative
Measure Participants	5179
At 6 months	1.8
At 1 year	1.5
At 2 years	-0.1
At 3 years	-0.7
At 4 years	-1.2
At 5 years	-1.6

Adverse Events

Time Frame	5 years
Adverse Event Reporting Description	SAEs were collected as part of the Primary Composite Outcome
Arm/Group Title	Invasive Strategy (INV)		Conservative Strategy
Arm/Group Description	Invasive Strategy (INV)		Conservative Strategy
All Cause Mortality
	Invasive Strategy (INV)		Conservative Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/2588 (5.6%)		144/2591 (5.6%)
Serious Adverse Events
	Invasive Strategy (INV)		Conservative Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	318/2588 (12.3%)		352/2591 (13.6%)
Cardiac disorders
Cardiovascular Death	92/2588 (3.6%)	92	111/2591 (4.3%)	111
Procedural Myocardial Infarction	70/2588 (2.7%)	70	24/2591 (0.9%)	24
Non-procedural Myocardial Infarction	130/2588 (5%)	130	196/2591 (7.6%)	196
Hospitalization for Unstable Angina	16/2588 (0.6%)	16	32/2591 (1.2%)	32
Hospitalization for Heart Failure	51/2588 (2%)	51	25/2591 (1%)	25
Resuscitated Cardiac Arrest	5/2588 (0.2%)	5	5/2591 (0.2%)	5
Stroke	45/2588 (1.7%)	45	38/2591 (1.5%)	38
Other (Not Including Serious) Adverse Events
	Invasive Strategy (INV)		Conservative Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2588 (0%)		0/2591 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.