Similar MACCE in Coronary Patients With Diabetes and CKD Treated With CABG or PCI
This sets the stage for the upcoming ISCHEMIA-CKD trial, one of the first real looks at revascularization in patients with chronic kidney disease.
In diabetic patients with stable ischemic heart disease, rates of MACCE and mortality are higher after coronary revascularization with either PCI or surgery when chronic kidney disease (CKD) is present, according to a new pooled analysis of three large trials. The study also showed a trend toward lower MACCE and fewer repeat revascularizations with CABG, but the researchers say the inconclusive nature of the findings illustrates the need for more individualized treatment of this high-risk subset.
“It raises the issue that diabetic patients need to be studied exclusively,” lead investigator Michael E. Farkouh, MD (University of Toronto, Canada), said in an interview with TCTMD. “This may be a poster child for individualized precision medicine.”
Unlike in the setting of diabetes and multivessel disease but no kidney disease, where the data favor CABG as the best revascularization strategy, the path is not clear for patients with diabetes, ischemic heart disease, and CKD. “We may find markers down the road that tell us which way to go,” Farkouh said. “But even with 5,000 patients, which is the largest cohort we have, we were unable to answer the question reliably.”
For the study, published online ahead of the February 5, 2019, issue of the Journal of the American College of Cardiology, Farkouh and colleagues examined data from BARI 2D, COURAGE, and FREEDOM on 4,953 patients with diabetes (21.4% with CKD) who underwent revascularization or were treated with optimal medical therapy (OMT).
Over 4.5 years of follow-up, MACCE risk was greater in patients with versus without CKD (adjusted HR 1.48; 95% CI 1.28-1.71), as was the risk of death (adjusted HR 1.69; 95% CI 1.40-2.05). When patients were categorized by extent of CKD, MACCE was significantly higher for both mild disease (adjusted HR 1.25; 95% CI 1.05-1.47) and moderate-to-severe disease (adjusted HR 2.26; 95% CI 1.83-2.80).
While CABG was associated with lower MACCE rates when compared with PCI in patients without CKD (adjusted HR 0.69; 95% CI 0.55-0.85), there was no significant difference in risk of MACCE between revascularization strategies in patients with CKD (P = 0.11). The findings remained the same regardless of whether CKD was mild or moderate-to-severe, although there was a nonsignificant trend toward lower MACCE with CABG in the latter group (adjusted HR: 0.68; 95% CI: 0.39 to 1.19).
Rates of subsequent revascularization were lower with CABG compared with PCI in patients without CKD (adjusted HR 0.38; 95% CI 0.30-0.48) as well as in those with mild CKD (adjusted HR 0.30; 95% CI 0.17-0.54) and moderate-to-severe CKD (adjusted HR 0.17; 95% CI 0.06-0.44).
To TCTMD, Farkouh said that even though repeat revascularization is generally a minor issue for patients without kidney disease, for those who have it the added potential risk of nephrotoxicity and acute kidney injury must be carefully weighed, and renal endpoints should be tracked to help researchers better evaluate the risks and benefits.
All Eyes on ISCHEMIA-CKD
In an editorial accompanying the study, David Faxon, MD, and Natalia C. Berry, MD (both Brigham and Women’s Hospital, Boston, MA), note several limitations of the pooled study. These include: older- and newer-generation stents were grouped together in the PCI analysis; contemporary surgical techniques and medications for diabetes treatment were not available; an analysis pertaining to cause of death and differentiating cardiac from non-cardiac death was lacking; there was a small number of patients in the CKD subgroups, particularly in the severe range; and the researchers did not adjust insulin dependence or type or dose of oral therapy for diabetes.
“Ultimately, further and more robust study is needed for a better understanding of to what degree CKD affects outcomes in revascularization,” Faxon and Berry write.
One upcoming study that could shed more light on the issue is ISCHEMIA-CKD, a randomized trial running in parallel with the main ISCHEMIA trial. ISCHEMIA-CKD is comparing OMT alone vs PCI or CABG in patients with advanced CKD or end-stage renal disease.
To TCTMD, Farkouh said the new paper “sets the stage” for ISCHEMIA-CKD by highlighting the existence of equipoise in the severe CKD patients studied to date. “We don't have the answers because we've largely excluded [these patients] from trials,” he added.
Farkouh said concerns about causing further kidney injury and short estimated potential survival for patients with moderate-to-severe CKD compared with patients without kidney disease has resulted in biases on the part of both interventionalists and cardiac surgeons that have resulted in their exclusion from the pivotal clinical trials, thus limiting the body of literature about management strategies and outcome expectations.
"We need to be willing to enroll our patients in clinical trials because we've probably left a lot of people behind,” he noted. Farkouh said his hopes are high that ISCHEMIA-CKD will provide needed answers, but if it is not conclusive, "then we really are going to have to find a new way to study these patients."
Farkouh ME, Sidhu MS, Brooks MM, et al. Impact of chronic kidney disease on outcomes of myocardial revascularization in patients with diabetes. J Am Coll Cardiol. 2019;73:400-411.
Faxon D, Berry NC. Best revascularization strategies in patients with CKD and DM: still uncertain. J Am Coll Cardiol. 2019;73:412-414.
- The study was supported by a grant from Gilead Sciences.
- Farkouh, Faxon, and Berry report no relevant conflicts of interest.