This interview was recorded on November 16, 2019, at the American Heart Association Scientific Sessions and is a collaboration between MDedge and Medscape. It is published on both websites.
This transcript has been edited for clarity.
Bruce Jancin: I'm Bruce Jancin with MDedge Cardiology News, and I'm speaking with Dr John Spertus of the Mid America Heart Institute about the practice-changing and really remarkable ISCHEMIA study. Almost 5200 patients were randomized. Tell us the high points.
John A. Spertus, MD: First of all, ISCHEMIA questioned and challenged current practice in many parts of the United States and throughout the world. We have an a priori belief that offering revascularization may confer some benefit in terms of preventing a heart attack or death, particularly in patients with high-risk disease. The cornerstone of stratifying risk and identifying those high-risk patients, where we think the benefits would be greater, has traditionally been stress imaging studies or other types of stress tests, depending on where around the world these tests are conducted. We took the patients with the highest risk, excluding those with left main disease, and randomized them to the cath lab to get whatever they needed. When they went to the cath lab, they defined anatomy and a team would decide whether this patient would be better treated with angioplasty, bypass surgery, or medical therapy alone.
Jancin: These were all patients with stable ischemic heart disease.
Spertus: That's very important. And that really mirrors practice today in that once the coronary anatomy is defined on an angiogram, we go straight to revascularization. Randomizing beforehand gives us the opportunity to implement this before we put a patient on a table and do an angiogram. If we found that revascularization was beneficial, we would continue to do what we're doing, but if we found that a conservative strategy of aggressive medical therapy was as good, it would be very awkward to take the patient off the table. So this pre-cath randomization was very important in allowing the results to be applied going forward.
ISCHEMIA was designed to look at major clinical events very carefully: adjudicated heart attacks, strokes, heart failure, sudden cardiac death, unstable angina, and mortality. The second key outcome was quality of life. When we looked at the main outcome of death, myocardial infarction, heart failure, unstable angina, and sudden cardiac death over the course of 4 years of observation, there was no difference between the groups. I say that with a small asterisk because there were absolutely overlapping curves for death. Myocardial infarctions, which were the largest driver of the endpoint, tended to occur more often in the invasive group for the first 2 years and more often in the conservative group in the second 2 years. So the curves crossed. That creates some statistical challenges, but the net net is that at 4 years, there were very comparable rates between the groups, and there was a large resonating belief in the room that we have to follow over a longer period of time to see whether the curves further diverge and there is a substantial difference at 5, 6, 7, 8, 10 years.
That being said, a lot of our treatment of patients is trying to help them over the next several years. The study found, importantly, that there was a very significant benefit in terms of angina control, physical function, and quality of life with an invasive strategy. That benefit was seen not only early after randomization at 3 months, but also at 1 and 3 years, and that sustained benefit has not really been seen before. A very important caveat is that patients who had no angina within a month of being randomized got no benefit. The people who clearly benefited in the short run from this invasive approach were the patients who had angina to begin with.
The take-home message for me as a practicing cardiologist is that I don't have to feel that I am doing any harm by trying medicines first to see if it can control their symptoms—even in the highest-risk patients with myocardial ischemia. If it does control their symptoms, then I view that as victory. If their symptoms persist or bother them, I can go to angiography and revascularization, knowing that I have not altered their risk of dying or having a heart attack in the short run. I tried medicines, so if they have a complication of the procedure, at least we tried everything else first.
It really opens up a new era of shared decision-making, and ISCHEMIA is providing very comforting evidence that we have time to work with our patients to try alternative approaches to control their symptoms and optimize their quality of life. And with that, I think we can all have confidence that now we can build the tools to help implement these findings and try to tailor the treatment to the risks, goals, and values of our patients.
Jancin: This will be a practice-changing study for sure. Do you think there will be waves of interventional cardiologists who decide that they need to get a new gig and learn how to do revascularization of peripheral arterial disease, for example?
Spertus: I suspect not. It's challenging for the interventional community because we need a lot of interventionalists to provide 24/7 call for ST-elevation myocardial infarction. But I do think that this will decrease the frequency of angioplasty in stable coronary disease, primarily in the patients who are asymptomatic. We estimate that somewhere between 20% and 25% of patients are probably asymptomatic undergoing angioplasty and bypass surgery.
It's not clear—unless there is a long-term follow-up that shows a much longer-term advantage—that there is a benefit from those procedures for the patients. Yes, that may lead to a decrease in the number of procedures, but about 75% or more of our procedures are done for acute coronary syndromes. I don't think there is anything in ISCHEMIA that will influence the bulk of revascularization procedures that are done. But in the stable cohort, I think it will. It should drop, frankly.
Jancin: Your investigative team got admirable rates of guideline-directed medical therapy adherence. Maybe more than in clinical practice.
Spertus: The rates were higher than in clinical practice but it was still disappointing. We still were not able to get 95%-plus of patients on all of the recommended therapies—the intense statins, the antiplatelets, the beta-blockers. Getting them to stop smoking is very difficult; increasing physical activity and weight loss is very difficult. It's challenging to do optimal medical therapy.
Despite that, for the degree that we did accomplish it, we showed very favorable outcomes across the board and as good as an invasive revascularization strategy. A lot of work is needed to figure out new and better incentive programs for patients to adhere to recommended therapies, to stop smoking, to engage in activities. We've got to get better at using and sustaining the lifestyle and disease-modifying therapies that are now available. I think this provides maybe not a direct incentive to do that, but we certainly should be leaning toward that. It's the foundation of any therapy we offer our patients.
Jancin: That is the news from the American Heart Association on ISCHEMIA, a trial that caused enormous numbers of cardiologists in the main hall to gasp and suck in their breath.
Spertus: Thank you very much.
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Cite this: John Spertus, MD, on the Practice-Changing ISCHEMIA Trial - Medscape - Nov 19, 2019.