ISCHEMIA-CKD EXTEND: revascularization does not improve outcomes at 5 years in patients with advanced chronic kidney disease
Reported from ESC Congress 2022
Panagiotis Xaplanteris reports on the ISCHEMIA-CKD EXTEND trial results - clinical outcomes at 5 years of follow-up, which were presented during the ESC 2022 congress in Barcelona.
Patients with advanced chronic kidney disease constitute one of the most challenging populations for revascularization due to the diffuse nature of atherosclerotic disease, comorbidities and high rates of adverse outcomes. The ISCHEMIA-CKD trial, an ancillary study of the main ISCHEMIA trial, had reported in 2020 that the 2-year outcomes of revascularization in this patient population did point towards any benefit in terms of survival, future myocardial infarctions nor did it improve symptoms, thus questioning the elective use of CABG/PCI in advanced CKD patients. The findings of the extended 5-year follow-up of the trial were presented in a hotline session at the ESC 2022 congress.
The trial enrolled patients with eGFR less than 30 mL/min/1.73 m2 of body surface area or on dialysis and moderate or severe ischemia assessed by scintigraphy, CMR, dobutamine echo or stress test. Of note, CT angiography was not recommended as a screening test to exclude left main disease in order to minimize the risk of acute kidney injury. 777 patients were randomized in a 1:1 fashion to either the invasive strategy group, receiving CABG or PCI plus OMT or to the conservative strategy group receiving only OMT. Data were analyzed with both frequentist and Bayesian methods; all analyses for events at five years point to no benefit of the interventional approach over the conservative one as regards all-cause mortality and cardiovascular mortality. Data regarding anginal symptoms at 5 years were not presented at this time.
A number of key points and details related to trial design and interpretation of results should be kept in mind:
- The event rate at 5 years is high, with almost 40% of patients dying during this period mostly from cardiovascular disease. This is despite the use of contemporary optimal medical therapy and close follow-up. Taking into account that this comes from the largest trial to date aiming at the CKD population with concomitant coronary artery disease and that patients usually fare worse outside the setting of a clinical trial, these data highlight the urgent need for therapies aiming to reduce hard endpoints.
- Revascularization, be that with CABG or PCI, does not improve overall or cardiovascular survival in patients with advanced CKD and angiographically significant CAD. Similarly, it does not decrease the incidence of future myocardial infarctions in a 5-year horizon. It seems that revascularization is “too little, too late” for this population with significant disease burden and comorbidities.
- As patients were not screened with coronary CT before their randomization, many of them randomized to the invasive treatment arm had diffuse coronary artery disease not amenable to revascularization, thus not receiving the allocated treatment. At 3 years, only 50.2% of the invasive strategy group were actually revascularized (85% with PCI and 15% with CABG). Multivessel disease was present in half of the patients, with involvement of the proximal LAD in 57% of them.
- Regarding relief from anginal symptoms, there was no benefit from revascularization at 2 years as per the initial ISCHEMIA CKD paper. Though data from the 5-year follow-up were not reported, a late benefit should not be expected as such an effect had only been seen early after revascularization procedures in previous trials, with this waning over time.
In conclusion, elective revascularization procedures for patients with advanced chronic kidney disease and stable coronary artery disease do not impact total and cardiovascular mortality, nor the development of future myocardial infarctions. The rate of events remains high, raising the question of whether relief from ischemia with “focal” therapies is of benefit in such patients with multiorgan diffuse atherosclerotic disease.
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