ISCHEMIA-CKD: No Improvement in CV Outcomes With Invasive vs Conservative Strategy

Sripal Bangalore, MD

An initial invasive strategy does not demonstrate a reduced risk of clinical outcomes as compared with an initial conservative strategy in patients with moderate ischemia and advanced chronic kidney disease (CKD), investigators of the ISCHEMIA-CKD study reported at the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia. Additionally, a quality of life analysis failed to demonstrate a positive impact with the invasive approach.

Cardiovascular disease is the leading cause of death in patients with CKD, who carry a 15-30 times higher risk than the age-adjusted cardiovascular mortality rate in the general population.

Despite being at distinctly increased risk for cardiovascular events, patients with CKD have been systematically excluded from prior trials evaluating optimal medical therapy (OMT) with or without revascularization in patients with stable ischemic heart disease (SIHD).

But an international study evaluating comparative health effectiveness with medical and invasive approaches sought to solve that issue by focusing on patients with CKD. The findings of ISCHEMIA-CKD, presented in a late-breaking AHA session, will have great implications on guidelines, health policy, and clinical practice.

Investigators with New York University School of Medicine and the ISCHEMIA-CKD Research Group reported primary results of clinical outcomes, as well as a primary report of quality of life outcomes.

The National Heart, Lung, and Blood Institute-funded randomized trial assessed whether an initial invasive management strategy of coronary angiography and optimal revascularization with either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery (if feasible) added to OMT improves clinical outcomes in patients with advanced CKD and SIHD compared with a conservative strategy of OMT alone (with coronary angiography and revascularization reserved for failure of OMT).

The study defined advanced CKD as estimated glomerular filtration rate [eGFR] <30 ml/min/1.73m2 or on dialysis.

The primary end point was a composite of death or nonfatal myocardial infarction (MI).

Major secondary end points were a composite of death, nonfatal MI, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; and angina symptoms and quality of life, as assessed by the Seattle Angina Questionnaire.

A total of 777 participants were randomized 1:1 to receive either the invasive strategy (n=388) or the conservative strategy (n=389). Median patient age was 63 years, 31% were women, and 53% were on dialysis. Out of those who were not on dialysis, 86% had CKD stage 4 and 14% had CKD stage 5 at baseline.

Inclusion criteria comprised 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. Overall, the study had >80% power to detect 22% to 24% relative reduction in primary endpoint assuming an aggregate 4-year cumulative rate of approximately 41% to 48%.

After 3 years, the rate of death or MI was 36.4% with the invasive approach and 36.7% with optimal medical therapy alone (adjusted HR 1.01; 95% CI 0.79-1.29). The cumulative incidence of the major secondary end point was 39.7% in the conservative group vs. 38.5% in the invasive group after 3 years.

Presenter Sripal Bangalore, MD, of NYU Langone Health, noted that there was an increased rate of stroke in the invasive arm (HR 3.76; 95% CI 1.52-9.32). A composite safety endpoint of death or new dialysis was also more frequent in the invasive arm (HR 1.48; 95% CI 1.04-2.11).

John A. Spertus, MD, MPH

The authors noted study limitations, including low rates of revascularization in the invasive arm, and noted that, based on exclusion criteria, the trial results do not apply to patients with acute coronary syndromes within 2 months, highly symptomatic patients, or LVEF <35%.

In a separate quality of life analysis, presenter John A. Spertus, MD, MPH, of Saint Luke’s Mid America Heart Institute/UMKC, reported that, in patients with stable coronary artery disease, advanced CKD, and moderate to severe ischemia, there was no “substantial improvement in angina control and quality of life over time.”

The studies, “International Study of Comparative Health Effectiveness With Medical and Invasive Approaches- Chronic Kidney Disease (ISCHEMIA-CKD): Primary Results of Clinical Outcomes" and "International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches-Chronic Kidney Disease (ISCHEMIA-CKD): Primary Report Of Quality Of Life Outcomes," were presented Saturday, November 16. 2019, at AHA 2019.