International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Left Ventricular Dysfunction Trial (ISCHEMIA-LVD)

ISCHEMIA-LVD: International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Left Ventricular Dysfunction Trial

The ISCHEMIA-HF trial will randomize participants with multivessel coronary artery disease (CAD) with ejection fraction (EF) ≤40% in a 1:2:2 fashion to guideline-directed medical therapy (GDMT):coronary artery bypass grafting (CABG):percutaneous coronary intervention (PCI).

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Heart Failure; Cognitive Impairment
• Intervention / Treatment: Procedure: Guideline-directed medical therapy (GDMT); Procedure: Coronary artery bypass grafting (CABG); Procedure: Percutaneous coronary intervention (PCI).

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: S. Bangalore, MD; Phone Number: 212-263-5656; Email: Sripal.bangalore@nyulangone.org

Study Locations

• Brazil
  • International Study Site, Brazil
    • International Study Site
• India
  • International Study Site, India
    • International Study Site
• Korea, Republic of
  • International Study Site, Korea, Republic of
    • International Study Site
• Mexico
  • International Study Site, Mexico
    • International Study Site
• Poland
  • International Study Site, Poland
    • International Study Site
• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Left ventricular ejection fraction (LVEF) ≤ 40% within prior 6 months (any local measurement, made within the past 6 months using echocardiography, multigated acquisition (MUGA), computed tomography (CT) scanning, magnetic resonance imaging (MRI), or ventricular angiography is acceptable, provided no subsequent measurement above 40%)
• Participants with multivessel CAD (defined as severe 3 vessel disease or 2 vessel disease including left anterior descending (LAD) artery disease) on coronary CT angiography (CCTA) or invasive coronary angiography
• CAD amenable to either PCI or CABG as determined by the local heart team
• 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 able and willing to give written informed consent

Exclusion Criteria:

• Decompensated heart failure or cardiogenic shock in the past 48 hours prior to randomization
• Concomitant significant valvular heart disease requiring surgery
• Prior cardiac surgery
• Dementia with loss of capacity to consent (clinically evident or previously diagnosed)
• Stroke within the previous 6 months or spontaneous intracranial hemorrhage at any time
• History of noncompliance with medical therapy
• Life expectancy less than the duration of the trial due to non-cardiovascular comorbidity
• Pregnancy (known to be pregnant; to be confirmed before randomization, if applicable)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GDMT; Participants with multivessel coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) who are assigned to receive GDMT.	Procedure: Guideline-directed medical therapy (GDMT); Participants receive guideline-directed medical therapy (GDMT).
Experimental: CABG; Participants with multivessel coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) who are assigned to receive CABG.	Procedure: Coronary artery bypass grafting (CABG); Participants receive coronary artery bypass grafting (CABG).
Experimental: PCI; Participants with multivessel coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) who are assigned to receive PCI.	Procedure: Percutaneous coronary intervention (PCI).; Participants receive percutaneous coronary intervention (PCI).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Cognitive Score	A composite score of various cognitive measures. Note that the total score range, calculation and interpretation to be updated upon submission of study protocol/materials to NYU Grossman School of Medicine IRB.	Month 12
Kansas City Cardiomyopathy Questionnaire (KCCQ) Score	The KCCQ is an 8-item assessment of heart failure (HF)-related health status. The raw score is calculated using the response to each item; the total score transforms the raw score to a standardized score scaled from 0 to 100 and summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.	Month 12
Composite Number of: Death, Nonfatal Myocardial infarction (MI), Stroke, and Hospitalization for HF	Composite calculation of the number participants who experience death, nonfatal MI, stroke, or hospitalization for HF in each arm.	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Number of: Mild Cognitive Impairment (MCI), Probable Dementia or Persistent Disability	Composite calculation of the number of participants with MCI, probable dementia or persistent disability in each arm.	Month 12
Composite Number of: Death or Hospitalization for HF	Composite calculation of the number of participants who die or are hospitalized for HF in each arm.	Month 12
Composite Number of: Death or Hospitalization for Cardiovascular (CV) Cause	Composite calculation of the number of participants who die or are hospitalized due to CV-related causes in each arm.	Month 12
Seattle Angina Questionnaire (SAQ) Physical Limitations and Quality of Life Domain Score	The SAQ Physical Limitations and Quality of Life domain comprises 2 items of the SAQ corresponding with angina-related physical limitations and quality of life (QOL). The raw score is calculated using the response to each item; the total score transforms the raw score to a standardized score scaled from 0 to 100 and summarized in 25-point ranges where: 0 to 24 represents poor health status, 25 to 49 represents fair status, 50 to 74 represents good status, and 75 to 100 represents excellent status.	Month 12
Self-Care of Heart Failure Index (SCHFI)	The SCHFI is a 39-item questionnaire assessing HF patients' performance of self-care activities related to HF, including how often they complete self-care, how likely they are to perform certain activities, and how confident they feel in performing the activities. Each item is rated on a scale from 1-5; the total score is the sum of responses and ranges from 39-195. Higher scores indicate greater overall performance of self-care activities related to HF.	Month 12

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: S. Bangalore, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Heart Failure; Coronary Artery Disease; Ejection Fraction
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Failure; Ventricular Dysfunction, Left; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ventricular Dysfunction
• Other Study ID Numbers: Pending (Clinical Research Information Service)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Sripal.bangalore@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Sripal.bangalore@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No