R01HL149888

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial Extended Follow-Up (EXTEND) - Project Summary/Abstract

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Extended Follow-Up (EXTEND) is the long-term follow-up of randomized, surviving participants in ISCHEMIA. This NHLBI-supported trial 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 guidelines-based medical therapy (GBMT), or 2) an initial conservative strategy of GBMT.

The trial did not demonstrate a reduction in the primary endpoint with an initial invasive strategy. There was an excess of peri-procedural myocardial infarction (MI) and a reduction in spontaneous MI in the INV group. Prior evidence demonstrates that spontaneous MI carries a higher risk of subsequent death than peri-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 overall reduction in MI rates with an INV strategy did not emerge until after 2 years.

Therefore, based on the observed reduction in spontaneous MI, it is imperative to ascertain long-term vital status to provide patients and clinicians with robust evidence on whether INV strategy reduces CV and all-cause death over the long-term. With projected 728 CV deaths (1000 total), we have adequate power to detect a between-group difference. It is equally important to improve precision around the point estimate to rule out a benefit if none exists.

Regardless of the study findings, robust long-term mortality data have enormous implications for clinical guidelines and practice, as affirmed by independent experts who write and oversee the development of national guidelines, and who provided letters of support. We will also quantify the impact of nonfatal CV events on subsequent mortality in ISCHEMIA-EXTEND, construct a risk score for mortality using baseline deep phenotypic data, and provide estimates of the impact of INV in the highest risk subgroup – those with severe coronary artery disease for whom current practice guidelines recommend coronary artery bypass (CABG) to improve survival.

We have obtained all required approvals and 99% of consents. We are ready to conduct extended follow-up of death, including cause of death, on >99% of surviving participants resulting in 10-year median follow-up. We will ascertain vital status by participant/proxy contact every 6 months via telephone or email, or by searching high-quality national/regional health/death databases. Participant last contact date, date of death, cause of death, and source of information will be collected and entered into a web-based electronic data capture system.

Our excellent participant retention, adherence to protocol, data completeness and quality during the initial trial phase, and our subsequent progress, with required approvals and consents secured, assure confidence that the study will meet its goals.

New York University

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

New York, New York 100165818 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 377% from $2,112,022 to $10,079,314.