Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

Background: In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively).
Objectives: This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death.
Methods: Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified.
Results: A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy.
Conclusions: In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360).
Competing Interests: Funding Support and Author Disclosures This project was supported by grants from the National Institutes of Health grants U01H117904 and U01HL117905; Arbor Pharmaceuticals, LLC; and AstraZeneca Pharmaceuticals, LP. Devices or medications were provided by Abbott Vascular (previously St. Jude Medical, Inc); Medtronic, Inc; Phillips (previously Volcano Corporation); Omron Healthcare, Inc; Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Espero Pharmaceuticals; Merck Sharp and Dohme Corp; and Sunovion Pharmaceuticals. The manuscript contents are solely the responsibility of the authors and do not necessarily represent official views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the United States Department of Health and Human Services. Dr Sidhu has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received personal fees from AstraZeneca and Sanofi-Regeneron outside the submitted work. Dr Alexander has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Mr Huang has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Mathew has received grants from National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Newman has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr O’Brien has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Pellikka has received grants from National Heart, Lung, and Blood Institute during the conduct of the study. Dr Bockeria has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Briguori has received grants from the National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Kretov has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Mazurek has received grants from the National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Orso has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Roik has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Sajeev has received grants from National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Shutov has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Rockhold reports grants from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Bristol Myers Squibb, AstraZeneca, American Regent, Gates Foundation, and Eidos during the conduct of the study; has received consulting fees from Janssen, Clover, Doctor Evidence, and Intercept; and equity ownership in GlaxoSmithKline, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr Borrego has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Balter has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Stone has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received speaker honoraria from Pulnovo and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, and V-wave. Dr Chaitman has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received personal fees from Merck, NovoNordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor outside the submitted work. Dr Goodman has received grants and personal fees from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants and personal fees from Amgen; AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Bristol Myers Squibb/Pfizer, CSL Behring/PERFUSE, Daiichi Sankyo/American Regent/DCRI, Ferring, Novartis, and Regeneron/Sanofi; and has received personal fees from Esperion/C5, GlaxoSmithKline, HLS Therapeutics, Merck, NovoNordisk, and Servier outside the submitted work. Dr Fleg has reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Reynolds has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received nonfinancial support from Abbott Vascular, Siemens, and BioTelemetry outside the submitted work. Dr Maron has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Hochman is the principal investigator for the ISCHEMIA trial for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular; Medtronic, Inc; Abbott Laboratories (formerly St. Jude Medical, Inc); Royal Philips NV (formerly Volcano Corporation); Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Merck Sharp and Dohme Corp; Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc Espero BioPharma; and Amgen, Inc; and has received financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Bangalore has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants and personal fees from Abbott Vascular; and has received personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Lyubarova has reported that she has no relationships relevant to the contents of this paper to disclose.
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