Kidney Transplant List Status and ISCHEMIA-CKD Trial Outcomes

Quick Takes

  • In this post hoc analysis of ISCHEMIA-CKD, patients listed for kidney transplant were more likely than nonlisted patients to undergo coronary angiography, regardless of randomized treatment assignment (invasive vs. conservative management).
  • Angiography for nonprotocol-specified indications was performed in 29.2% of listed patients, as compared with 4.2% of nonlisted patients.
  • Treatment strategy was not associated with a difference in the primary composite outcome of all-cause mortality and nonfatal MI in either listed or nonlisted patients.

Study Questions:

Among kidney transplant candidates with a moderate or greater myocardial ischemia on noninvasive testing, does an invasive management strategy (coronary angiography and revascularization) improve clinical outcomes?

Methods:

This post hoc analysis of ISCHEMIA-CKD (International Study of Comparative Health Effectiveness of Medical and Invasive Approaches–Chronic Kidney Disease) compared clinical outcomes among patients listed for kidney transplant with those not listed for kidney transplant, according to a randomly assigned treatment strategy for coronary artery disease (CAD)—optimal medical therapy versus medical therapy plus coronary angiography and revascularization. All trial participants had chronic kidney diseases (CKD) with estimated glomerular filtration rate <30 ml/min/1.73 m2 and evidence of moderate or greater ischemia on noninvasive testing. Notable exclusion criteria were known left main disease, left ventricular ejection fraction ≤35%, New York Heart Association (NYHA) class III or IV heart failure, and unacceptable level of angina despite maximal medical therapy. The primary outcome was a composite of all-cause mortality and nonfatal myocardial infarction (MI) at 3 years. The secondary outcome was a composite of mortality, MI, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, and stroke.

Results:

Of the 777 trial participants, 194 were listed for kidney transplant and 583 were not listed. In the listed group, 51 patients (26%) received transplants during the trial (median follow-up period 2.4 years). Listed patients were younger (mean age 60 vs. 65 years), less likely to be of Asian race (15% vs. 29%), more likely to be on dialysis (83% vs. 44%), less likely to have severe ischemia on stress testing (30% vs. 41%), and more likely to be free of angina and symptomatic heart failure (Canadian Cardiovascular Society class 0, 47% vs. 29%; NYHA class I, 47% vs. 29%).

Patients listed for transplant were more likely than nonlisted patients to undergo coronary angiography and revascularization. In the conservative treatment arm, revascularization was performed in 16.2% of listed patients and 10.7% of nonlisted patients. In the invasive arm, revascularization was performed in 51.5% of listed patients and 45.6% of nonlisted patients. Angiography for non–protocol-specified indications was performed in 29.2% of listed patients, as compared with 4.2% of nonlisted patients. The primary outcome occurred in 32.1% of listed patients and 38.1% of nonlisted patients (log rank p = 0.15). Among listed patients, the primary outcome occurred in 28% of the invasive strategy group and 30% of the conservative strategy group (adjusted hazard ratio [aHR], 0.91; 95% confidence interval [CI], 0.54-1.54). Among nonlisted patients, the primary outcome occurred in 33% of the invasive group and 34% of the conservative group (aHR, 1.03; 95% CI, 0.78-1.37). The composite secondary outcome did not differ significantly according to listing status or treatment group (aHR for listed patients treated with invasive vs. conservative strategy, 0.89; 95% CI, 0.55-1.46; aHR for nonlisted patients, 1.17; 95% CI, 0.89-1.53).

Conclusions:

Among CKD patients with moderate or greater myocardial ischemia on noninvasive testing, an invasive approach to CAD management does not improve outcomes, regardless of kidney transplant listing status. These findings do not support routine coronary angiography and revascularization prior to kidney transplant.

Perspective:

Protocols for cardiovascular evaluation prior to kidney transplant listing in the United States vary considerably among centers and may be influenced by such factors as availability of testing, patient mix, and collaboration among specialists. This study is a valuable contribution to the literature, as there is a dearth of randomized controlled trials addressing CAD treatment in the prekidney transplant population. In light of the study findings, the practice of pursuing coronary revascularization in an asymptomatic transplant candidate with normal left ventricular systolic function, solely because of transplant candidacy, should be questioned—particularly since many patients who are listed for kidney transplant are not transplanted for several years, or at all. Mechanistically, postkidney transplant MI is often a supply–demand mismatch phenomenon, triggered by stressors such as hypotension, blood loss, and elevated intracardiac filling pressures in the setting of delayed graft function. Many patients with advanced CKD, particularly those with diabetes, have coronary microvascular dysfunction, which may increase risk of perioperative events even if complete epicardial revascularization has been achieved. Therefore, careful perioperative management of patients with known or suspected ischemic heart disease is always critically important. The ongoing CARSK (Canadian-Australian Randomized trial of Screening Kidney transplant candidates for coronary artery disease) trial will provide more guidance for care in this patient population, comparing CAD screening strategies in waitlisted patients (screening only on initial listing versus routine re-screening at regular intervals).

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, Angina, Unstable, Cardiac Surgical Procedures, Coronary Angiography, Coronary Artery Disease, Diagnostic Imaging, Exercise Test, Glomerular Filtration Rate, Heart Arrest, Heart Failure, Kidney Transplantation, Metabolic Syndrome X, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Renal Dialysis, Renal Insufficiency, Chronic, Secondary Prevention, Stroke, Stroke Volume, Ventricular Function, Left


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