Elsevier

American Heart Journal

Volume 205, November 2018, Pages 42-52
American Heart Journal

Trial Design
International Study of Comparative Health Effectiveness with Medical and Invasive Approaches–Chronic Kidney Disease (ISCHEMIA-CKD): Rationale and design

https://doi.org/10.1016/j.ahj.2018.07.023Get rights and content

Background

Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown.

Methods

ISCHEMIA-CKD is a National Heart, Lung, and Blood Institute–funded randomized trial designed to determine the comparative effectiveness of an initial invasive strategy (cardiac catheterization and optimal revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] plus OMT) versus a conservative strategy (OMT alone, with cardiac catheterization and revascularization [percutaneous coronary intervention or coronary artery bypass graft surgery, if suitable] reserved for failure of OMT) on long-term clinical outcomes in 777 patients with advanced CKD (defined as those with estimated glomerular filtration rate <30 mL/min/1.73m2 or on dialysis) and moderate or severe ischemia on stress testing. Participants were randomized in a 1:1 fashion to the invasive or a conservative strategy. The primary end point is a composite of death or nonfatal myocardial infarction. Major secondary endpoints are a composite of death, nonfatal myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; angina control; and disease-specific quality of life. Safety outcomes such as initiation of maintenance dialysis and a composite of initiation of maintenance dialysis or death will be reported. The trial is projected to have 80% power to detect a 22% to 24% reduction in the primary composite end point with the invasive strategy when compared with the conservative strategy.

Conclusions

ISCHEMIA-CKD will determine whether an initial invasive management strategy improves clinical outcomes when added to OMT in patients with advanced CKD and stable ischemic heart disease.

Section snippets

Methods

Funding from National Institutes of Health grants U01HL117904 and U01HL117905 was used to support the research and creation of this paper. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents.

Discussion

Patients with SIHD and advanced CKD are underrepresented in contemporary clinical trials comparing optimal coronary revascularization and medical therapy versus OMT alone, providing very limited data on management of these challenging patients. We considered including patients with advanced CKD in the ISCHEMIA trial, that is, having no eGFR exclusion criterion. The COURAGE trial was designed without a creatinine cutoff for trial entry, yet only 16 patients with advanced CKD were enrolled in

Disclosures

Dr Sripal Bangalore: ad hoc consultant/speaker: Abbott Vascular, Pfizer, Daiichi Sankyo, Merck, Medicines Company, Astra Zeneca; research grant: Abbott Vascular, NHLBI; travel grant: Boston Scientific, Medtronic.

Dr John Spertus: ad hoc consultant: United Healthcare, Novartis, Bayer, Janssen, AstraZeneca; research grant: Abbott Vascular; intellectual property: copyright to Seattle Angina Questionnaire; equity: Health Outcomes Sciences.

Dr Glenn M. Chertow: member, Board of Directors: Satellite

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    Michelle O'Shaughnessy, MD, served as guest editor for this article.

    RCT# NCT01985360.

    Funding source: The study was funded by the National Heart, Lung, and Blood Institute (U01HL117904, U01HL117905).

    Disclaimer: The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the United States Department of Health and Human Services.

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