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Randomized Controlled Trial
. 2021 Jul 27;78(4):348-361.
doi: 10.1016/j.jacc.2021.05.001. Epub 2021 May 11.

Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial

Charles A Herzog  1 , Mengistu A Simegn  2 , Yifan Xu  3 , Salvatore P Costa  4 , Roy O Mathew  5 , Mohammad C El-Hajjar  6 , Sanjeev Gulati  7 , Rafael A Maldonado  8 , Eric Daugas  9 , Magdelena Madero  10 , Jerome L Fleg  11 , Rebecca Anthopolos  3 , Gregg W Stone  12 , Mandeep S Sidhu  6 , David J Maron  13 , Judith S Hochman  3 , Sripal Bangalore  14
Affiliations
Randomized Controlled Trial

Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial

Charles A Herzog et al. J Am Coll Cardiol. .

Abstract

Background: Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing.

Objectives: In this post hoc analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness of Medical and Invasive Approaches-Chronic Kidney Disease), we compared outcomes of patients not listed versus those listed according to management strategy.

Methods: In the ISCHEMIA-CKD trial (n = 777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction) and secondary (death, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed.

Results: Compared with those not listed, listed patients were younger (60 years vs 65 years), were less likely to be of Asian race (15% vs 29%), were more likely to be on dialysis (83% vs 44%), had fewer anginal symptoms, and were more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios for the primary outcome were 0.91 (95% confidence interval [CI]: 0.54-1.54) and 1.03 (95% CI: 0.78-1.37) for those listed and not listed, respectively (pinteraction= 0.68). Adjusted hazard ratios for secondary outcomes were 0.89 (95% CI: 0.55-1.46) in listed and 1.17 (95% CI: 0.89-1.53) in those not listed (pinteraction = 0.35).

Conclusions: In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant. (ISCHEMIA-Chronic Kidney Disease Trial [ISCHEMIA-CKD]; NCT01985360).

Keywords: chronic kidney disease; coronary angiography; coronary revascularization; ischemic heart disease; kidney transplantation; medical therapy.

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Conflict of interest statement

Funding Support and Author Disclosures This work was funded by the National Institutes of Health (NIH) (grants U01HL117904 and U01HL117905). This project was supported by grants from Arbor Pharmaceuticals and AstraZeneca Pharmaceuticals. Devices or medications were provided by Abbott Vascular (previously St. Jude Medical), Medtronic, Phillips (previously Volcano Corporation), and Omron Healthcare. Medications provided by Arbor Pharmaceuticals, AstraZeneca Pharmaceuticals, Espero Pharmaceuticals, Merck Sharp & Dohme Corp., and Sunivion Pharmaceuticals. The 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 Department of Health and Human Services. Dr Herzog has received personal fees from the National Heart, Lung, and Blood Institute (NHLBI)/NIH during the conduct of the study; has received research grants from Amgen, Relypsa, Bristol Myers Squibb, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, University of British Columbia; and has received other support from Abbvie, Amgen, AstraZeneca, Corvidia, Diamedica, FibroGen, Janssen, NxStage, Pfizer, Relypsa, Sanifit, University of Oxford, Bristol Myers Squibb, UpToDate, Boston Scientific, General Electric, Johnson & Johnson, Merck, and Hennepin Healthcare. Drs. Simegn, Costa, Mathew, El-Hajjar, Gulati, Maldonao, Madero, Anthopolos, Maron, and Mr. Xu has received research grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Daugas has received personal fees from Amgen, GlaxoSmithKline, and AstraZeneca; has received grants from Agence Nationale pour la Recherche/ Direction Générale de l'Offre de Soins; and has received nonfinancial support from Amgen. Dr Fleg was an employee of the NHLBI during the conduct of the study. Dr Stone has received speaker or other honoraria from Cook and Terumo; has served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, Cardiomech, Elucid Bio, and Occlutech; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. Dr Sidhu has received research grants from the NHLBI during the conduct of the study; and has received personal fees from AstraZeneca and Sanofi-Regeneron. Dr. Hochman served as Principal Investigator for ISCHEMIA trial for which, in addition to support by NHLBI, devices and medications were provided by Abbott Vascular, Medtronic., St. Jude Medical, Volcano Corporation, Arbor Pharmaceuticals, AstraZeneca Pharmaceuticals, Merck Sharp & Dohme, and Omron Healthcare; and has received financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Bangalore has received research grants from the NHLBI during the conduct of the study; has received research grants from Abbott Vascular; and has received personal fees from Abbott Vascular, Biotronik, Pfizer, Amgen, and Reata.

Figures

Figure 1a.
Figure 1a.. Coronary angiography and revascularization in patients not listed for transplant.
Cumulative incidence of coronary angiography and revascularization by treatment arm in patients not listed for kidney transplant. The blue lines represent patients in the conservative arm and the red lines represent those in the invasive arm. The solid lines represent coronary angiography and the dashed lines represent revascularization. Abbreviations: CON cath=angiography/catheterization in conservative arm; CON revasc=revascularization in conservative arm; INV cath=angiography/catheterization in invasive arm; INV revasc=revascularization in invasive arm.
Figure 1b.
Figure 1b.. Coronary angiography and revascularization in patients listed for transplant.
Unadjusted cumulative incidence of coronary angiography and revascularization in patients who are listed for kidney transplant. The blue lines represent patients in the conservative arm and the red lines represent those in the invasive arm. The solid lines represent coronary angiography and the dashed lines represent revascularization. Abbreviations: CON cath=angiography/catheterization in conservative arm; CON revasc=revascularization in conservative arm; INV cath=angiography/catheterization in invasive arm; INV revasc=revascularization in invasive arm.
Figure 2a.
Figure 2a.. Primary outcome by list status.
Cumulative incidence function for the primary outcome (all-cause mortality/non-fatal myocardial infarction) in patients not listed (green) and listed (orange) for kidney transplant at study enrollment; number at risk at each time point is listed beneath the graph.
Figure 2b.
Figure 2b.. Forest plot of outcomes by transplant list status.
Forest plot presenting adjusted hazard ratios for the primary outcome and individual secondary outcomes in patients listed and not listed for kidney transplant; p<0.05 was considered statistically significant. Abbreviations: CI=confidence interval; HF=heart failure; HR=hazard ratio; MI=myocardial infarction; RCA=resuscitated cardiac arrest; UA=unstable angina.
Figure 3a.
Figure 3a.. Primary outcome by treatment arm in patients not listed.
Cumulative incidence of the primary outcome between randomized treatment arms in patients not listed for kidney transplant. The blue line represents those in the conservative arm; the red line represents those in the invasive arm. Number at risk at each time point is listed below the graph. Abbreviations: CON=conservative arm; INV=invasive arm.
Figure 3b.
Figure 3b.. Primary outcome by treatment arm in patients listed for transplant.
Cumulative incidence of the primary outcome between randomized treatment arms in patients listed for kidney transplant. The blue line represents those in the conservative arm; the red line represents those in the invasive arm. Number at risk at each time point is listed below the graph. Abbreviations: CON=conservative arm; INV=invasive arm.
Figure 3c.
Figure 3c.. Secondary outcome by treatment arm in patients not listed.
Cumulative incidence of secondary outcome between randomized treatment arms in patients not listed for kidney transplant. The blue line represents those in the conservative arm; the red line represents those in the invasive arm. Number at risk at each time point is listed below the graph. Abbreviations: CON=conservative arm; INV=invasive arm.
Figure 3d.
Figure 3d.. Secondary outcome by treatment arm in patients listed for transplant.
Cumulative incidence of secondary outcome between randomized treatment arms in patients not listed for kidney transplant. The blue line represents those in the conservative arm; the red line represents those in the invasive arm. Number at risk at each time point is listed below the graph. Abbreviations: CON=conservative arm; INV=invasive arm.
Central Illustration:
Central Illustration:. Kidney Transplant List Status and Outcomes in ISCHEMIA-CKD
Estimated cumulative incidence for primary and secondary outcomes by treatment strategy for participants listed for kidney transplant. Abbreviations: MI = Myocardial Infarction; UA = Unstable Angina; HF = Heart Failure; RCA = Resuscitated Cardiac Arrest; HR = Hazard Ratio; CI = Confidence Interval
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