ISCHEMIA-EXTENDed Follow-up
Study Details
Study Description
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. 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 an invasive strategy reduces CV and all-cause death over the long-term. With projected 728 CV deaths we have adequate power to detect a between-group difference in mortality. 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 the invasive strategy in the highest risk subgroup - those with severe coronary artery disease for whom current practice guidelines recommend coronary artery bypass (CABG) to improve survival.
SPECIFIC AIMS
Aim 1. To assess whether an initial invasive strategy reduces long-term 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.
Aim 2. To assess the impact of nonfatal events on long-term CV and all-cause mortality
Aim 3. To construct risk scores for CV and all-cause mortality using phenotypic data including clinical factors, stress test findings, and details of coronary anatomy.
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 CV and all-cause 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.
DESIGN NARRATIVE, INCLUDING MODIFICATIONS DURING THE TRIAL:
We will conduct a long-term ascertainment of CV and all-cause mortality for surviving ISCHEMIA participants. The limited follow-up after the observed reduction in spontaneous MI events suggests that the completed period of follow-up was not long enough to observe a mortality benefit, and makes it imperative to assess long-term CV and all-cause mortality to provide patients and clinicians with robust evidence regarding 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, we will provide estimates on the impact of INV in the highest risk subgroup, those with coronary artery anatomy for whom current practice guidelines recommend CABG to improve survival (3-vessel CAD and 2-vessel CAD with proximal LAD stenosis). Equally important is to improve precision around the point estimate of the treatment effect for CV and all-cause mortality for the trial overall and in important subgroups to efficiently maximize the substantial investment by of NHLBI, patients, and study teams for relatively small additional investment.
Furthermore, understanding of the impact of nonfatal events on subsequent CV and all-cause mortality among patients with SIHD will influence the design of CV clinical trials for years to come. MI is the most frequently occurring endpoint in CV trials and with the ever-increasing sensitivity of biomarker assays for MI, it is of paramount importance to understand the relationship between MI type and definition and subsequent death. The ISCHEMIA-EXTEND dataset will thus afford a unique opportunity to inform patients, physicians, and researchers about multiple aspects of the care of patients with SIHD. Primary Endpoint: CV mortality.
Vital status data will be collected in a rigorous manner either 1) from high-quality vital statistics registries, or 2) by contacting participants and their next of kin
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Invasive Strategy (INV) Routine invasive strategy with cardiac catheterization followed by revascularization plus optimal medical therapy. |
Procedure: cardiac catheterization
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.
Other Names:
Procedure: coronary artery bypass graft surgery
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.
Other Names:
Procedure: percutaneous coronary intervention
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.
Other Names:
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| 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
diet, physical activity, smoking cessation
Other Names:
Drug: Medication
antiplatelet, statin, other lipid lowering, antihypertensive, and anti-ischemic medical therapies
Other Names:
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Outcome Measures
Primary Outcome Measures
- Cumulative Event Rate of Death From Cardiovascular Causes [13 years]
median of 10 years; years (range 7.5-13 years)
Secondary Outcome Measures
- Cumulative Event Rate of Death From Any Cause [5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
• Alive at the end of the initial follow-up period for ISCHEMIA
Exclusion Criteria:
N/A
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- NYU Langone Health
- New York University
- Stanford University
- National Heart, Lung, and Blood Institute (NHLBI)
- Duke University
- University of Missouri, Kansas City
Investigators
- Study Chair: Judith S Hochman, MD, New York University
- Principal Investigator: David J Maron, MD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 11-00498-2