PHILADELPHIA – Coronary revascularization in patients with stage 4 or 5 chronic kidney disease (CKD) and stable ischemic heart disease accomplishes nothing constructive, according to clear-cut results of the landmark ISCHEMIA-CKD trial.
In this multinational randomized trial including 777 stable patients with advanced CKD and moderate or severe myocardial ischemia on noninvasive testing, an early invasive strategy didn’t reduce the risks of death or ischemic events, didn’t provide any significant improvement in quality of life metrics, and resulted in an increased risk of stroke, Sripal Bangalore, MD, reported at the American Heart Association scientific sessions.
“said Dr. Bangalore, professor of medicine and director of complex coronary intervention at New York University.
This was easily the largest-ever trial of an invasive versus conservative coronary artery disease management strategy in this challenging population. For example, in the COURAGE trial of optimal medical therapy with or without percutaneous coronary intervention for stable coronary disease (N Engl J Med. 2007 Apr 12;356:1503-16), only 16 of the 2,287 participants had an estimated glomerular filtration rate below 30 mL/min per 1.73 m2.
Of note, the participating study sites received special training aimed at minimizing the risk of acute kidney injury after cardiac catheterization in this at-risk population. The training included utilization of a customized left ventricular end diastolic volume–based hydration protocol, guidance on how to perform percutaneous coronary intervention with little or no contrast material, and encouragement of a heart/kidney team approach involving a cardiologist, nephrologist, and cardiovascular surgeon. This training really paid off, with roughly a 7% incidence of acute kidney injury after catheterization.
“The expected rate in such patients would be 30%-60%,” according to Dr. Bangalore.
The primary endpoint in ISCHEMIA-CKD was the rates of death or MI during 3 years of prospective follow-up. This occurred in 36.7% of patients randomized to optimal medical therapy alone and 36.4% of those randomized to an early invasive strategy. Similarly, the major secondary endpoint, comprising death, MI, and hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, was also a virtual dead heat, occurring in about 39% of subjects. More than 27% of study participants had died by the 3-year mark regardless of how their coronary disease was managed.
The adjusted risk of stroke was 3.76-fold higher in the invasive strategy group; however, the most strokes were not procedurally related, and the explanation for the significantly increased risk in the invasively managed group remains unknown, the cardiologist said.
John A. Spertus, MD, who led the quality of life assessment in ISCHEMIA-CKD and in the 5,129-patient parent ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), also presented at the AHA scientific sessions. He reported that, unlike in the parent study, there was no hint of a meaningful long-term quality of life benefit for revascularization plus optimal medical therapy, compared with that of optimal medical therapy alone, in ISCHEMIA-CKD.
“We have greater than 93% confidence that there is more of a quality of life effect in patients without advanced CKD than in patients with advanced CKD,” said Dr. Spertus, director of health outcomes research at the Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri, Kansas City.
Discussant Glenn L. Levine, MD, hailed ISCHEMIA-CKD as “a monumental achievement,” an ambitious, well-powered study with essentially no loss of follow-up during up to 4 years. It helps fill an utter void in the AHA/American College of Cardiology guidelines, which to date offer no recommendations at all regarding revascularization in patients with CKD because of a lack of evidence. And he considers ISCHEMIA-CKD to be unequivocally practice changing and guideline changing.
“Based on the results of ISCHEMIA-CKD, I will generally not go searching for ischemia and [coronary artery disease] in most severe and end-stage CKD patients, absent marked or unacceptable angina, and will treat them with medical therapy alone,” declared Dr. Levine, professor of medicine at Baylor College of Medicine and director of the cardiac care unit at the Michael E. DeBakey VA Medical Center, both in Houston.
He offered a few caveats. Excluded from participation in ISCHEMIA-CKD were patients with acute coronary syndrome, significant heart failure, or unacceptable angina despite optimal medical therapy at baseline, so the study results don’t apply to them. Also, the acute kidney injury rate after intervention was eye-catchingly low.
Dr. Bangalore discussed the ISCHEMIA-CKD trial and outcomes in a video interview with Medscape’s Tricia Ward.
“It seems unlikely that all centers routinely do and will exactly follow the very careful measures to limit contrast and minimize contrast nephropathy used in this study,” Dr. Levine commented.
ISCHEMIA-CKD, like its parent ISCHEMIA trial, was funded by the National Heart, Lung, and Blood Institute. Dr. Bangalore reported having no relevant financial interests. Dr. Spertus holds the copyright for the Seattle Angina Questionnaire, which was used for quality of life measurement in the trials. Dr. Levine disclosed that he has no relations with industry or conflicts of interest.