ISCHEMIA-EXTEND (Extended Follow-up)

NCT04894877 | Active Not Recruiting DMC

• 2 other identifiers: 11-00498-21R01HL149888
• Study Type: observational
• Target: 5,391
• Locations: 0 countries
• Sites: N/A

Brief Summary

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up (ISCHEMIA-EXTEND) is the long-term follow-up of randomized, surviving participants in ISCHEMIA. ISCHEMIA was an NHLBI-supported trial that randomized 5,179 participants with stable ischemic heart disease to two different management strategies: 1) an initial invasive strategy (INV) of cardiac catheterization and revascularization when feasible plus guideline-directed medical therapy (GDMT), or 2) an initial conservative strategy (CON) of GDMT. The trial did not demonstrate a reduction in the primary endpoint with an initial invasive strategy. There was an excess of procedural myocardial infarction (MI) and a reduction in spontaneous MI in the INV group. Prior evidence suggests that spontaneous MI carries a higher risk of subsequent death than procedural MI. There was a late separation in the cardiovascular (CV) mortality curves over a median of 3.2 years follow-up in ISCHEMIA. The MI incidence curves crossed at approximately 2 years. However, during the trial follow-up phase there were excess non-CV deaths in the invasive strategy. Therefore, it is imperative to ascertain long-term vital status to provide patients and clinicians with robust evidence on whether there are differences between management strategies and to increase precision around the treatment effect estimates for risk of all-cause, CV and non-CV death over the long-term. Overarching Goal: To assess the effect of an initial invasive strategy on long-term all-cause, CV and non-CV mortality compared with an initial conservative strategy in SIHD patients with at least moderate ischemia on stress testing, over 10 years median follow-up. Condition: Coronary Disease Procedure: Observational Phase: Phase III per NIH Condition: Cardiovascular Diseases Procedure: Observational Phase: Phase III per NIH Condition: Heart Diseases Procedure: Observational Phase: Phase III per NIH

Conditions

Cardiovascular Diseases; Coronary Disease; Coronary Artery Disease; Heart Diseases; Myocardial Ischemia

Outcome Measures

Primary Outcomes (3)

• Cumulative Event Rate of Death: All-Cause

  Cumulative event rate of death from all causes.

  Year 10 (Range: 6-13 years)

• Cumulative Event Rate of Cardiovascular (CV) Death

  Cumulative event rate of death from cardiovascular causes.

  Year 10 (Range 6-13 years)

• Cumulative Event Rate of Non-CV Death

  Cumulative event rate of death from non-cardiovascular causes.

  Year 10 (Range: 6-13 years)

Secondary Outcomes (1)

• Cumulative Event Rate of Death by High Risk Subgroups

  Year 10 (Range 6-13 years)

Study Arms (2)

Active Comparator: Invasive Strategy (INV)

Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy.

Procedure: cardiac catheterization; Procedure: coronary artery bypass graft surgery; Procedure: percutaneous coronary intervention

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; Drug: Medication

Interventions

cardiac catheterization PROCEDURE

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.

Also known as: Cath

Active Comparator: Invasive Strategy (INV)

coronary artery bypass graft surgery PROCEDURE

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.

Also known as: CABG

Active Comparator: Invasive Strategy (INV)

percutaneous coronary intervention PROCEDURE

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.

Also known as: PCI

Active Comparator: Invasive Strategy (INV)

Lifestyle BEHAVIORAL

diet, physical activity, smoking cessation

Also known as: Behavior change

Active Comparator: Conservative Strategy

Medication DRUG

antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies

Also known as: Pharmacologic Therapy

Active Comparator: Conservative Strategy

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants of the ISCHEMIA main trial that meet the EXTEND inclusion criteria

You may qualify if:

• Alive at the end of the initial follow-up period for ISCHEMIA

You may not qualify if:

• Participants who withdrew consent during initial trial phase
• Participants who declined participation in long-term follow-up

Sponsors & Collaborators

• NYU Langone Health: lead
• New York University: collaborator
• Stanford University: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Duke University: collaborator

Related Publications (1)

• Hochman JS, Anthopolos R, Reynolds HR, Bangalore S, Xu Y, O'Brien SM, Mavromichalis S, Chang M, Contreras A, Rosenberg Y, Kirby R, Bhargava B, Senior R, Banfield A, Goodman SG, Lopes RD, Pracon R, Lopez-Sendon J, Maggioni AP, Newman JD, Berger JS, Sidhu MS, White HD, Troxel AB, Harrington RA, Boden WE, Stone GW, Mark DB, Spertus JA, Maron DJ; ISCHEMIA-EXTEND Research Group. Survival After Invasive or Conservative Management of Stable Coronary Disease. Circulation. 2023 Jan 3;147(1):8-19. doi: 10.1161/CIRCULATIONAHA.122.062714. Epub 2022 Nov 6.

  PMID: 36335918 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Coronary Disease; Coronary Artery Disease; Heart Diseases; Myocardial Ischemia

Interventions

Cardiac Catheterization; Coronary Artery Bypass; Percutaneous Coronary Intervention; Dosage Forms; Drug Therapy

Condition Hierarchy (Ancestors)

Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Catheterization; Therapeutics; Investigative Techniques; Myocardial Revascularization; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Thoracic Surgical Procedures; Endovascular Procedures; Minimally Invasive Surgical Procedures; Pharmaceutical Preparations; Technology, Pharmaceutical

Study Officials

• Judith S Hochman, MD

  New York University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: May 20, 2021
• Study Start: July 1, 2012
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article