# The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial EXTENDed Follow-up (EXTEND)

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $2,112,022

## Abstract

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 s...

## Key facts

- **NIH application ID:** 10121264
- **Project number:** 1R01HL149888-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Judith S Hochman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,112,022
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121264

## Citation

> US National Institutes of Health, RePORTER application 10121264, The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial EXTENDed Follow-up (EXTEND) (1R01HL149888-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10121264. Licensed CC0.

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