Jeffrey Berger, MD: Key Differences in ISCHEMIA and ISCHEMIA-CKD Results

With a seemingly endless amount of data from clinical trials with well-controlled patient populations being released at major meetings, the long-awaited release of ISCHEMIA and ISCHEMIA-CKD was welcomed by clinicians across specialties at AHA 2019.

International Study of Comparative Health Effectiveness with Medical and Invasive Approaches examined whether invasive strategies or conservative strategies were more ideal for the management of stable ischemic heart disease.

ISCHEMIA included 5179 patients from 37 countries with moderate to severe ischemia. Values including median age (64; 58, 70), hypertension (73%), previous myocardial infarction (19%), and systolic (130) and diastolic blood pressure (77; 70, 81) were similar in both study groups. Inclusion criteria required patients to have 50% or greater stenosis in a major epicardial vessel—as measured by stress imaging—and 70% or greater stenosis in a proximal or mine vessel—as measured by exercise tolerance test.

ISCHEMIA-CKD included a total of 777 participants randomized 1:1 to receive either strategy. Inclusion criteria required at least moderate ischemia on an exercise or pharmacologic stress test and end-stage renal disease on dialysis or estimated glomerular filtration rate (eGFR) <30mL/min/1.73m². Median patient age was 63 years, 31% were women, and 53% were on dialysis.

ISCHEMIA revealed there were no significant advantages in terms of preventing cardiovascular events but significant improvements in quality of life was noted among patients randomized to the invasive strategy. Conversely, ISCHEMIA-CKD demonstrated no significant differences in quality of life or patient outcomes based on which strategy they were randomized to at baseline. &#8232;&#8232;

For more on the key differences in the results of ISCHEMIA and ISCHEMIA-CKD, MD Magazine® sat down with study investigator Jeffrey Berger, MD, associate professor of Medicine and Surgery and director of Center for Prevention of Cardiovascular Disease, for his perspective.

MD Mag: What are the key differences in the results of ISCHEMIA and ISCHEMIA-CKD?

Berger: ISCHEMIA and ISCHEMIA-CKD, in my opinion, are trials that will have a very enduring effect. It really teaches us how we should be taking care of patients with stable ischemic heart disease. So very importantly, ISCHEMIA looked at patients that had at least moderately abnormal stress testing, who had normal kidney function defined as a creatinine clearance of greater than 30.

In the ISCHEMIA trial overall, there was no significant benefit in terms of the prevention of a cardiovascular event, but very importantly, there was an important and I think the very significant quality of life benefits—so, patients felt better.

In the ISCHEMIA-CKD trial, it really asked a similar question but in a very under-studied population It asked in patients who have severe kidney disease or those with a creatinine clearance of less than 30 or who are on dialysis—does a does an invasive strategy beat out a conservative strategy among those with at least moderate ISCHEMIA on a stress test? In the ISCHEMIA CKD trial, there was no benefit in the clinical endpoints, but very importantly, there was no advantage towards reducing quality of life.

So, I think overall, there is a different message in both the ISCHEMIA and the ISCHEMIA-CKD trial. ISCHEMIA, while it showed no benefit in its overall composite of cardiovascular events, there was a very important benefit in terms of quality of life. And in the ISCHEMIA-CKD trial, there really was no benefit either in terms of their primary efficacy endpoint, or in terms of quality of life.

I think another very important difference is that in ISCHEMIA-CKD among those who had severely abnormal kidney disease—and who were not on dialysis&mdash;If you were stratified if you were randomized into the invasive strategy, you are more likely to require dialysis over the long term. That's a very important consideration when thinking about bringing these patients into the catheterization laboratory.