ISCHEMIA CKD: No Difference In Outcomes Between Medical and Invasive Approaches to Ischemia in Patients with End Stage Renal Disease

The results of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches – Chronic Kidney Disease were presented by Dr. Sripal Bangalore at the American Heart Association 2019 meeting. Dr. Bangalore and his team showed that in patients with moderate ischemia and end-stage renal disease, an initial invasive strategy with catheterization and possibly percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) did not lead to an improvement in clinical outcomes.

Prior trials that investigated the efficacy of an invasive strategy in patients with ischemia have typically excluded patients with end-stage renal disease. Therefore, the utility of a more invasive strategy initially in these patients remained to be unknown. In this study, patients with end-stage renal disease (as defined by an estimated glomerular filtration rate of less than 30 mL/min/1.73m) and at least moderate ischemia on exercise or pharmacologic stress testing to either an invasive strategy or optimal medical therapy. Exclusion criteria included a left ventricular ejection fraction of less than 35%, New York Heart Association Class 3 or 4, unacceptable levels of angina despite maximal medical therapy, recent acute coronary syndrome within the last 2 months, or revascularization procedures within the last 12 months. The primary outcome of the study was time to death or myocardial infarction by 3 years. The major secondary endpoint was a composite of death, MI, hospitalization for unstable angina, heart failure or resuscitated cardiac arrest. Safety outcomes included the initiation of maintenance dialysis or death.

A total of 777 patients were enrolled (388 randomized to the invasive arm and 389 to the conservative arm). Patients were followed for a median of 2.5 years. The primary composite outcome (MI or death) occurred in 36.7% of patients in the conservative group and 36.4% of patients in the invasive group (HR 1.01, 95% CI 0.79-1.29). Additionally, there was no difference in the incidence of the major secondary endpoint between the two groups (39.7% in the conservative group vs 38.5% in the invasive group, HR 1.02, 95% CI 0.79-1.29). With the exception of the stroke rate, there were no differences in the individual components of the secondary endpoint. The stroke rate was found to be higher in the invasive group (HR 3.76, 95% CI 1.52-9.32, p = 0.004). As for the prespecified safety endpoint of death or new dialysis, the rate of this composite endpoint was higher in the invasive group (HR 1.48, 95% CI 1.04-2.11, p= 0.02).

In an interview with Dr. C. Michael Gibson, Dr. Bangalore discussed the findings of the trial. He noted, “We saw that these patients had a very high event rate. The 3-year death or MI rates were 36%. Interestingly, this was not different between the invasive and conservative strategies. This was also true for the major secondary endpoint.” Additionally, he said, “our primary endpoint of death or MI was mainly driven by death. In the ISCHEMIA trial, CV death or MI was mainly driven by MIs. There were very few deaths.” Dr. Bangalore noted that the majority of deaths in this study were attributed to cardiovascular death, but said that this was a very broad definition.

It is important to note that the study does have its limitations. There were low rates of revascularization in the invasive arm. Additionally, these findings do not apply to patients with a recent ACS, patients with severe symptoms, or patients with a left ventricular ejection fraction of less than 35%. This is the largest trial to date that compares invasive and conservative strategies in patients with end-stage renal disease and ischemia.

Click here to view the study slides.

Click here to see Dr. Gibson’s discussion with Dr. Bangalore.