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  • CV Death Is More Prevalent than Non-CV Death in Advanced CKD Patients: ISCHEMIA-CKD Analysis

    In patients with advanced chronic kidney disease (CKD) who had moderate to severe ischemia on stress testing, cardiovascular mortality was more common than death with non-cardiovascular or undetermined cause, a new analysis shows.

    Additionally, sudden cardiac death and infection were the most common reasons for cause-specific deaths, according to a prespecified secondary analysis from the ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches–Chronic Kidney Disease)) trial.

    These findings were reported in a manuscript by Mandeep S. Sidhu, MD, of Albany Medical College, New York, and colleagues published Monday online and in the Jan. 23 edition of JACC: Cardiovascular Interventions.

    ISCHEMIA-CKD was an investigator-initiated, international, randomized trial in patients with advanced CKD (defined as an estimated glomerular filtration rate [eGFR] of <30 ml per minute per 1.73 m2 of body-surface area or the receipt of dialysis) and moderate or severe myocardial ischemia.

    The trial demonstrated that an initial invasive strategy added to guideline-directed medical therapy (GDMT) did not reduce the risk of cardiovascular events than an initial conservative strategy of GDMT alone during a median follow up of 2.2 years. The prespecified secondary analysis report overall and cause-specific death by treatment strategy and were analyzed using Cox models adjusted for baseline covariates. Three-year cumulative incidences were calculated for the adjudicated cause of death.

    Of 777 patients, 585 were alive (75.3%) and 192 patients (24.7%) died during the median follow up of 2.2 years. Of these, 94 patients (12.1%) had died of a documented cardiovascular cause, 59 patients (7.6%) died of a non-cardiovascular cause, and 39 patient deaths (5.0%) were considered to be of undetermined cause.

    At baseline, patients with cardiovascular mortality were more likely to be older, were diabetics with a prior history of myocardial infarction (MI), peripheral artery disease, prior coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting), heart failure, or reduced left ventricular ejection fraction (LVEF; <50%) compared to those alive at the end of follow-up. Baseline GDMT was not different among patients who survived or died. Of patients were alive at follow-up, 52.1% were on dialysis, and of patients who had died of any cause, 57.3% were on dialysis.

    The study demonstrated that the 3-year cumulative incidence of cardiovascular death did not differ among the invasive and conservative groups (14.6% vs 12.6%, respectively; hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.75-1.70). The rate of non-cardiovascular death was also comparable between the invasive and conservative cohorts (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of cardiovascular deaths) and infection (54.2% of non-cardiovascular deaths) were the most common cause-specific deaths that did not vary by the initial randomized treatment strategy.

    The key limitations of the study were modest sample size and short follow-up duration. The authors stated that the study results should not be extrapolated to patients who were excluded, including patients with reduced LVEF <35%, recent acute coronary syndrome within the prior 2 months, recent stroke within 6 months or PCI within 12 months and post-renal transplant.

    In an accompanying editorial, Hitinder S. Gurm, MD and George Hanna, MD of University of Michigan, emphasized that the most effective survival-enhancing therapy for patients with advanced CKD is renal transplant, meaning that every patient should be evaluated for renal transplant.

    They further stated that management of coronary artery disease in advanced CKD patients continues to be a challenge for cardiologists because of limited evidence, and the current analysis is a major step forward in overcoming this gap. This subject remains an important avenue for future research, the editorialists added.


    Sidhu MS, Alexander KP, Huang Z, et al. Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial. JACC Cardiovasc Interv 2023;16:209–218.

    Gurm HS, Hanna G. Improving Cardiac Outcomes Among Patients With Severe Chronic Kidney Disease: The Quest Continues. JACC Cardiovasc Interv 2023;16:219–221.

    Image Credit: Rasi –

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