Skip to content

Results of the ISCHEMIA trial, a Late-Breaking Science Session from the 2019 AHA Meeting

In This Article

  • The ISCHEMIA trial examined whether patients with stable ischemic heart disease benefit from revascularization in addition to optimal medical therapy
  • No difference in outcome (including death and myocardial infarction) was found in the two groups at three years after randomization
  • For those with frequent and severe angina, there was a greater quality of life improvement for patients treated invasively with revascularization
  • The outcomes suggest that patients with stable ischemic heart disease should first be treated with guideline-directed medical therapy before exploring more invasive options
  • Cost-benefit analyses have yet to be completed, but could suggest that the findings will impact health care costs by reducing unnecessary catheterizations and revascularizations

For patients with myocardial ischemia, treatment options include medical therapy or more invasive procedures such as percutaneous coronary revascularization or coronary artery bypass surgery. Prior studies of stable ischemic heart disease patients with all degrees of myocardial ischemia (including mild) showed no benefit to a revascularization strategy, but some some observational data had suggested the treatment might benefit those with the most severe degrees of myocardial ischemia.

A multicenter randomized controlled study of the treatment strategies for patients with stable ischemic heart disease, named the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, examined whether patients with stable ischemic heart disease who demonstrate moderate or severe myocardial ischemia on stress testing would benefit from revascularization in addition to the improvements provided by optimal medical therapy. The results of trial were presented as a Late-Breaking Science Session at the American Heart Association 2019 Meeting.

Michael H. Picard, MD, a staff cardiologist in the Corrigan Minehan Heart Center at Massachusetts General Hospital, was an investigator on the ISCHEMIA trial, where he directed the echocardiography core lab and interpreted the stress echocardiograms. His research focuses on the applications of echocardiography in coronary artery disease, valvular heart disease and translational cardiology, and aims to determine factors found in non-invasive cardiac imaging that can identify the risks of patients with coronary artery disease. In this Q&A, he discusses the outcomes and implications of the study.

Q: What led you to your current research?

Picard: I have been collaborating with the principal investigator of the trial, Judith Hochman, MD, of NYU Langone, and serving as the echocardiography core lab for her trials for many years. Since one of the areas of my research is focused on the use of echocardiography in coronary artery disease, the goals of this trial align with mine.

Q: What was the aim of the ISCHEMIA trial?

Picard: The ISCHEMIA trial examined whether patients with stable ischemic heart disease who demonstrate moderate or severe myocardial ischemia on stress testing would benefit from initial revascularization in addition to the improvements provided by optimal medical therapy. While prior studies that enrolled patients with all degrees of myocardial ischemia (including mild) showed no benefit to the revascularization strategy, there are some observational data suggesting a benefit of revascularization might exist for those with the more severe degrees of myocardial ischemia.

Q: What was the design of the ISCHEMIA trial?

Picard: In the ISCHEMIA trial, over 8,000 patients were enrolled from around the world. These patients had stable symptoms (no acute coronary syndrome within the prior two months, no progressive or accelerating symptoms, etc.) and had to demonstrate at least moderate myocardial ischemia on functional stress testing. I served as the director of the echocardiography core lab for the trial and interpreted the stress echocardiograms that were performed as one of these functional tests. They also had to have left ventricular ejection fraction (LVEF) > 35%. If they met these entry criteria, they underwent a coronary CT angiogram to make sure they did not have left main coronary artery disease. And then, over 5,100 patients were randomized to receive either guideline-directed medical therapy or medical therapy plus an invasive strategy, which included coronary angiography and revascularization when appropriate either by percutaneous or surgical approaches. Thus the results apply to those with stable ischemic heart disease, LVEF > 35% and no left main coronary artery disease.

Q: What were the results of the trial?

Picard: When the data are examined there was no difference in outcome (death, myocardial infarction [MI], hospitalization for MI, heart failure or resuscitated sudden cardiac death) between the two groups. Importantly, deaths during the mean of 3.3 years were low and the main component of the adverse events was MIs (some related to the invasive procedures early and then spontaneous MI later).

When quality of life was examined, the major determinant was the frequency of angina. Patients in both arms of the trial had improvements in quality of life as their angina frequencies were reduced. However, for those with frequent angina—daily or weekly—there was a greater improvement in those in the invasive arm and a higher probability of abolishing angina symptoms with revascularization as opposed to medical therapy alone.

Q: What is the impact for treating patients?

Picard: Clinicians can be reassured. Patients are not dying after high-risk stress tests (as evidenced in the medical therapy arm). So if a patient with stable symptoms has a high-risk test, there is no need to rush urgently to the cath lab.

Every patient should be carefully evaluated and treated on an individual basis, but it seems reasonable that most patients who meet the profile of those in this trial should start with guideline-directed medical therapy. If that does not take care of their symptoms, then shared decision-making with the patient is the next step to decide if catheterization and potential revascularization should be performed. For patients like those in this trial, the invasive strategy does not save lives or allow people to live longer but it does improve quality of life by reducing angina (in those with frequent angina).

For patients with stable ischemic heart disease without frequent angina, as long as the LVEF is >35% and there is no left main disease, there does not seem to be a need for coronary angiography and revascularization.

Q: Could you describe how the results could impact the costs associated with health care?

Picard: The cost-benefit analysis of the trial will be forthcoming. For now, one could hypothesize that for this outpatient population, there will be fewer catheterizations and revascularizations and probably an increase in coronary CT angiography. If this change in practice occurs, there should be a reduction in costs by reducing unnecessary invasive procedures.

Q: Are there any knowledge gaps or further opportunities for study?

Picard: When one looks at the event curves at the later points in time, the two curves appear to be diverging with fewer events in the invasive arm. A longer-term follow-up will be important to see if this difference in outcome becomes significant.

There are several other points to be considered:

  • It's important to remember that these data apply to a specific group of stable ischemic heart disease patients and not those with unstable or progressive symptoms
  • All of the stress tests, ECG and events were adjudicated by blinded core labs and event committees, so the study did not rely on the local site interpretations and was not subject to local site biases
  • About 25% of the patients in the conservatively treated arm crossed over to the invasive strategy during the trial

Learn more about the Corrigan Minehan Heart Center

Refer a patient to the Corrigan Minehan Heart Center

Related topics

Related

Myocardial injury carries a worse prognosis than MI and warrants a thorough evaluation for its underlying precipitant.

Related

In this video, Hanna Gaggin, MD, MPH, discusses her research in discovering biomarkers of patients with preserved ejection fraction. She hopes that more progress will be made in finding treatment options for patients with type 2 myocardial infarction.