Cardiovascular DiseasesNCT04894877
ISCHEMIA-EXTEND (Extended Follow-up)
An observational study of Cardiovascular Diseases and Coronary Disease, run by NYU Langone Health.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Cardiovascular Diseases, Coronary Disease, Coronary Artery Disease
- What is being tested?
- cardiac catheterization, coronary artery bypass graft surgery and percutaneous coronary intervention
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- How many people
- 5,391 participants
- Where
- No sites listed yet
- Study dates
- Jul 2012to 31 Mar 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants of the ISCHEMIA main trial that meet the EXTEND inclusion criteria
Who may be able to join
- Alive at the end of the initial follow-up period for ISCHEMIA
Who cannot join
- Participants who withdrew consent during initial trial phase
- Participants who declined participation in long-term follow-up
About this study
Official title: International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up
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:
Read more
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
Read the detailed description
The primary goals of all therapies are to enable patients to feel better and/or live longer. ISCHEMIA provided definitive data on the benefit of INV on quality of life. However, mortality is the most objective and compelling clinical outcome. Strategies that reduce deaths over the long term are of greatest interest to patients and physicians. Long-term follow-up of the ISCHEMIA trial cohort to assess all-cause, CV and non-CV mortality by treatment group is particularly important given that the primary results show relatively late crossing of the event curves, an overall reduction in spontaneous MI with INV, and late divergence of CV death curves in favor of the INV strategy but with an excess of non-CV deaths.
DESIGN NARRATIVE, INCLUDING MODIFICATIONS DURING THE TRIAL:
The investigators will conduct a long-term ascertainment of all-cause, CV and non-CV mortality for surviving ISCHEMIA participants. The limited follow-up after the observed reduction in spontaneous MI events may not have been long enough to observe a mortality benefit, and this makes it imperative to assess long-term all-cause, CV and non-CV mortality to determine whether an initial invasive strategy reduces the risk of death years later, as seen in other trials with crossing curves, e.g., STICH, a randomized trial comparing a strategy of surgical revascularization to GDMT alone in patients with SIHD and LVEF <35%.
Furthermore, with additional accrual of deaths, the investigators will provide estimates on the impact of INV in the highest risk subgroup, those with coronary artery anatomy for whom practice guidelines have recommended CABG to improve survival (3-vessel CAD and 2-vessel CAD with proximal LAD stenosis). Equally important is to improve precision around the point estimates of the treatment effect for all-cause, CV and non-CV mortality for the trial overall and in important subgroups to efficiently maximize the substantial investment by of NHLBI, patients, and study teams.
Vital status data will be collected in a rigorous manner from high-quality vital statistics registries, medical records, or by contacting participants and their next of kin.
ISCHEMIA-EXTEND will also follow eligible participants from the NHLBI-funded ISCHEMIA-CKD trial with the same methodology as for the main trial with separate analyses. They will be referred to as ISCHEMIA-EXTEND for the main trial and ISCHEMIA-CKD EXTEND for the CKD trial.
PARTICIPATING COUNTRIES:
North America: Canada; Mexico; USA South America: Argentina; Brazil; Peru Asia: China; India; Japan; Malaysia; Singapore; 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
- Conditions
- Cardiovascular Diseases, Coronary Disease, Coronary Artery Disease, Heart Diseases, Myocardial Ischemia
- Being tested
- cardiac catheterization, coronary artery bypass graft surgery, percutaneous coronary intervention, Lifestyle, Medication
- Medical subject headings
- Cardiovascular Diseases, Coronary Disease, Coronary Artery Disease, Heart Diseases, Myocardial Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cardiac catheterizationProcedure or surgery
Also called Cath
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.
coronary artery bypass graft surgeryProcedure or surgery
Also called CABG
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.
percutaneous coronary interventionProcedure or surgery
Also called PCI
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.
LifestyleBehavioural
Also called Behavior change
diet, physical activity, smoking cessation
MedicationDrug
Also called Pharmacologic Therapy
antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
| Study group | Role | What they receive |
|---|---|---|
| Active Comparator: Invasive Strategy (INV) | Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. Receives: 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. Receives: Behavioral: Lifestyle; Drug: Medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Event Rate of Death: All-Cause
Cumulative event rate of death from all causes.
Measured: Year 10 (Range: 6-13 years)
Cumulative Event Rate of Cardiovascular (CV) Death
Cumulative event rate of death from cardiovascular causes.
Measured: Year 10 (Range 6-13 years)
Cumulative Event Rate of Non-CV Death
Cumulative event rate of death from non-cardiovascular causes.
Measured: Year 10 (Range: 6-13 years)
Secondary outcomes (1)
Cumulative Event Rate of Death by High Risk Subgroups
Angiographic and clinical risk variables.
Measured: Year 10 (Range 6-13 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2021
- Study startJul 2012
- Primary completion31 Mar 2026 (estimated)
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5,391 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- New York University, Stanford University, National Heart, Lung, and Blood Institute (NHLBI), Duke University
- Responsible party
- Sponsor
- Investigators
- Judith S Hochman, MD, Principal investigator, New York University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04894877
- Sponsor's protocol ID
- 11-00498-2
- Other IDs
- 1R01HL149888
- Status last verified
- Jan 2026
- First submitted
- 18 May 2021
- Last updated
- 29 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data from the follow-up analysis will be made available 2 years after the main results paper is published.
Publications
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.
PubMed 36335918
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) Extended Follow-up
- ClinicalTrials.gov ID
- NCT04894877
- Acronym / sponsor ID
- 11-00498-2
- Conditions
- Cardiovascular Diseases, Coronary Disease, Coronary Artery Disease, Heart Diseases, Myocardial Ischemia
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 5,391 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- New York University, Stanford University, National Heart, Lung, and Blood Institute (NHLBI), Duke University
- Study start
- Jul 2012 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 20 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
The primary goals of all therapies are to enable patients to feel better and/or live longer. ISCHEMIA provided definitive data on the benefit of INV on quality of life. However, mortality is the most objective and compelling clinical outcome. Strategies that reduce deaths over the long term are of greatest interest to patients and physicians. Long-term follow-up of the ISCHEMIA trial cohort to assess all-cause, CV and non-CV mortality by treatment group is particularly important given that the primary results show relatively late crossing of the event curves, an overall reduction in spontaneous MI with INV, and late divergence of CV death curves in favor of the INV strategy but with an excess of non-CV deaths.
DESIGN NARRATIVE, INCLUDING MODIFICATIONS DURING THE TRIAL:
The investigators will conduct a long-term ascertainment of all-cause, CV and non-CV mortality for surviving ISCHEMIA participants. The limited follow-up after the observed reduction in spontaneous MI events may not have been long enough to observe a mortality benefit, and this makes it imperative to assess long-term all-cause, CV and non-CV mortality to determine whether an initial invasive strategy reduces the risk of death years later, as seen in other trials with crossing curves, e.g., STICH, a randomized trial comparing a strategy of surgical revascularization to GDMT alone in patients with SIHD and LVEF <35%.
Furthermore, with additional accrual of deaths, the investigators will provide estimates on the impact of INV in the highest risk subgroup, those with coronary artery anatomy for whom practice guidelines have recommended CABG to improve survival (3-vessel CAD and 2-vessel CAD with proximal LAD stenosis). Equally important is to improve precision around the point estimates of the treatment effect for all-cause, CV and non-CV mortality for the trial overall and in important subgroups to efficiently maximize the substantial investment by of NHLBI, patients, and study teams.
Vital status data will be collected in a rigorous manner from high-quality vital statistics registries, medical records, or by contacting participants and their next of kin.
ISCHEMIA-EXTEND will also follow eligible participants from the NHLBI-funded ISCHEMIA-CKD trial with the same methodology as for the main trial with separate analyses. They will be referred to as ISCHEMIA-EXTEND for the main trial and ISCHEMIA-CKD EXTEND for the CKD trial.
PARTICIPATING COUNTRIES:
North America: Canada; Mexico; USA South America: Argentina; Brazil; Peru Asia: China; India; Japan; Malaysia; Singapore; 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Comparator: Invasive Strategy (INV) | – | Procedure: cardiac catheterization, Procedure: coronary artery bypass graft surgery, Procedure: percutaneous coronary interventionRoutine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. |
| Active Comparator: Conservative Strategy | – | Behavioral: Lifestyle, Drug: MedicationOptimal medical therapy with cardiac catheterization and revascularization reserved for patients with acute coronary syndrome, ischemic heart failure, resuscitated cardiac arrest or refractory symptoms. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants of the ISCHEMIA main trial that meet the EXTEND inclusion criteria
Key inclusion criteria (1 listed)
- Alive at the end of the initial follow-up period for ISCHEMIA
Key exclusion criteria (2 listed)
- Participants who withdrew consent during initial trial phase
- Participants who declined participation in long-term follow-up
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cardiac catheterizationAlso: CathNarrowed 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. | Procedure or surgery | Active Comparator: Invasive Strategy (INV) |
| coronary artery bypass graft surgeryAlso: CABGArtery 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. | Procedure or surgery | Active Comparator: Invasive Strategy (INV) |
| percutaneous coronary interventionAlso: PCIPercutaneous 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. | Procedure or surgery | Active Comparator: Invasive Strategy (INV) |
| LifestyleAlso: Behavior changediet, physical activity, smoking cessation | Behavioural | Active Comparator: Conservative Strategy |
| MedicationAlso: Pharmacologic Therapyantiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies | Drug | Active Comparator: Conservative Strategy |
Primary outcome
Cumulative Event Rate of Death: All-Cause
Time frame: Year 10 (Range: 6-13 years)
Cumulative event rate of death from all causes.
Cumulative Event Rate of Cardiovascular (CV) Death
Time frame: Year 10 (Range 6-13 years)
Cumulative event rate of death from cardiovascular causes.
Cumulative Event Rate of Non-CV Death
Time frame: Year 10 (Range: 6-13 years)
Cumulative event rate of death from non-cardiovascular causes.
1 secondary outcome
Cumulative Event Rate of Death by High Risk Subgroups
Time frame: Year 10 (Range 6-13 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Derived from this study: PubMed 36335918Hochman 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.
- Individual participant dataSharing planned: Yes. Data from the follow-up analysis will be made available 2 years after the main results paper is published.
Related trials for Cardiovascular Diseases
Recruiting
EVERO Drug-coated Balloon (DCB) Randomized Trial
Peripheral Vascular Disease, Peripheral Arterial Disease
Recruiting
Systematic Ambulatory ECG Monitoring Following TAVI
Aortic Stenosis, Conduction Disturbances
Recruiting
Postural Mobilization Compared to Noradrenaline Only in Off-Pump CABG Surgery
Coronary Artery Disease With Need for Bypass Surgery, Coronary Artery Disease(CAD)
Enrolling by invitation
Optical Coherence Tomography in Acute Vessel Evaluation
Ischemic Heart Disease, Ischemic Coronary Artery Disease
Active, not recruiting
Safety and Efficacy Evaluation of the iNstroke 4F Thromboaspiration Catheter in Patients With Acute Ischaemic Stroke Due to Primary Distal Medium Vessel Occlusions (DMVO)
Acute Ischemic Stroke
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith S Hochman, MD principal investigator
New York University
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Coronary Disease, run by NYU Langone Health.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative Event Rate of Death: All-Cause (time frame: Year 10 (Range: 6-13 years)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04894877, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2026.