Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial
Selected in JACC by M. Alasnag
ISCHEMIA-CKD is the only contemporary randomized trial that prospectively evaluated an upfront strategy of coronary angiography and revascularization plus optimal medical therapy (OMT) compared with OMT alone in patients listed for renal transplant.
References
Authors
Charles A. Herzog , Mengistu A. Simegn , Yifan Xu , Salvatore R. Costa , Roy O. Mathew , Mohammad C. El-Hajjar , Sanjeev Gulati , Rafael A. Maldonado , Eric Daugas , Magdelena Madero , Jerome L. Fleg , Rebecca Anthopolos , Gregg W. Stone , Mandeep S. Sidhu , David J. Maron , Judith S. Hochman , and Sripal Bangalore
Reference
https://doi.org/10.1016/j.jacc.2021.05.001
Published
May 2021
Link
Read the abstractReviewer
My Comment
Why this study? – the rationale/objective
The latest American and European guidelines have identified chronic kidney disease (CKD) as a risk enhancer for atherosclerotic cardiovascular disease 1. There has always been an emphasis on intensive preventive measures in this population. As these patients are listed for renal transplant, extensive work up often includes ischemia testing or invasive cardiac catheterization for risk stratification. However, the risk assessment is usually not sufficient for decision making in clinical practice and many of these patients undergo revascularization if obstructive disease is identified under the assumption that it reduces perioperative events. This practice is very common and is based on small, randomized data of 26 insulin dependent diabetic patients generated by Manske et al. el that reported a significant benefit in the primary composite endpoint of unstable angina, myocardial infarction (MI), or cardiac death.2 A much larger randomized trial, CARP Trial, that is often quoted by the cardiology community, noted no difference in mortality and perioperative morbidity in patients with critical limb ischemia who undergo pre-emptive coronary revascularization. This trial, however, did not examine patients with CKD specifically and does not reflect contemporary practice.3 Accordingly, the ISCHEMIA-CKD (International Study of Comparative Health Effectiveness of Medical and Invasive Approaches–Chronic Kidney Disease) sought to shed light on this issue more definitively.
How was it executed? – the methodology
ISCHEMIA-CKD is the only contemporary randomized trial that prospectively evaluated an upfront strategy of coronary angiography and revascularization plus optimal medical therapy (OMT) compared with OMT alone in patients listed for renal transplant. This analysis was post-hoc and obtained from ISCHEMIA-CKD comparing outcomes of patients not listed versus those listed according to the assigned management strategy. CKD patients with chronic coronary syndromes (CCS) and at least moderate ischemia were enrolled (both listed for transplant and not listed). The primary endpoint was a composite of all-cause mortality or nonfatal MI and the secondary endpoints were death, nonfatal MI, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke. These were recorded out to three years.
What is the main result and the relevance for clinical practice
The study does not support preemptive coronary angiography and revascularization of patients undergoing renal transplant evaluation. This is in keeping with several meta-analyses and the age-old CARP trial. It is important to recognize that OMT today has evolved and includes intensive prognosis altering medications such as statins, beta blockers, and angiotensin converting enzyme inhibitors further confirming the outcomes of this trial that intensified the OMT.
Several caveats need to be highlighted, however. Firstly, the ischemia testing was based on nuclear scintigraphy which has lower accuracy in CKD. In addition, after adjustment for baseline variables, patients listed for transplant had better outcomes than those not listed which is explained by the selection bias of healthier individuals for transplantation. It should be noted that those listed were twice as likely to undergo angiography and revascularization. The crossover rate in the conservative arm of those listed was 33% (i.e. underwent revascularization). Furthermore, only a small percent of those listed underwent renal transplantation during the study which does not allow concrete conclusions with respect to a reduction in perioperative events. I suspect this will be an ongoing point of contention with the transplant community. Finally, one must recall the exclusion criteria of the main ISCHEMIA trial, low ejection fraction, left main disease, and severe inducible ischemia. As such, the trial does not provide guidance for these higher risk patients and a more patient centered discussion with the transplant team becomes necessary.
Related content: Mirvat Al Asnag interviews David J Maron about the results of the ISCHEMIA-CKD (Chronic Kidney Disease) trial - AHA 2019
References:
- Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Jun 25;73(24):3168-3209. doi: 10.1016/j.jacc.2018.11.002. Epub 2018 Nov 10. Erratum in: J Am Coll Cardiol. 2019 Jun 25;73(24):3234-3237. PMID: 30423391.
- Manske CL, Wang Y, Rector T, Wilson RF, White CW. Coronary revascularisation in insulin-dependent diabetic patients with chronic renal failure. Lancet 1992;340:998-1002.
- Raghunathan A, Rapp JH, Littooy F, Santilli S, Krupski WC, Ward HB, Thottapurathu L, Moritz T, McFalls EO; CARP Investigators. Postoperative outcomes for patients undergoing elective revascularization for critical limb ischemia and intermittent claudication: a subanalysis of the Coronary Artery Revascularization Prophylaxis (CARP) trial. J Vasc Surg. 2006 Jun;43(6):1175-82. doi: 10.1016/j.jvs.2005.12.069. PMID: 16765234.
- Fleisher LA, Fleischmann KE, Auerbach AD et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130:2215-45.
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