CANTOS Data Show Importance of Inflammation Risk in CKD Patients with Atherosclerosis


Paul M. Ridker, MD, discusses the latest findings from the canakinumab trial before highlighting his team's work with ziltevekimab in ZEUS.

Despite current guideline recommendations, new analysis from the canakinumab-based CANTOS trial show residual inflammation may be a greater target to treat than residual cholesterol in patients with atherosclerotic disease and impaired kidney function.

The findings, presented at the American College of Cardiology (ACC) 2022 Scientific Sessions in Washington, DC, this weekend, highlight the need for altered treatment mindsets—and more available novel therapies—among clinicians treating patients with both chronic kidney disease (CKD) and atherosclerosis.

In an interview with HCPLive during ACC 2022, study author Paul M. Ridker, MD, of Brigham and Women’s Hospital and Harvard Medical School, explained how it’s been long-established that coinciding residual cholesterol and inflammatory risks persist in patients with atherosclerosis.

“These 2 processes are very different, they both need to be addressed to get the greatest benefits for our patients, but most clinicians are measuring cholesterol, so they know who has residual cholesterol risk, but relatively few are measuring high-sensitivity CRP,” Ridker said. “And it’s like anything else in medicine: if you don’t measure it, you can’t actually treat it and we don’t know what’s going on with the patient.”

Ridker explained the CANTOS analysis team’s rationale as wanting to better interpret the predictive outcome of treatable biomarkers in these patients, regardless of CKD status.

“If I don’t even measure CRP, I don’t know what their problem is,” Ridker explained. “But I’m probably measuring their LDL because the guidelines say you should do that. But we have evidence here that what these patients need past their high-intensity statin may not be another lipid-lowering agent—they may need something that targets inflammation.”

This finding presents more problems, Ridker said: ideal inflammation-targeting therapies are limited in use for patients with kidney disease. Solutions may need to go beyond the IL-1 targeting canakinumab and standard lifestyle intervention.

“In the short run, the answer is that if you have a patient with CKD and residual inflammatory risk, we know that diet, exercise, smoking cessation all are effective, and I would still lower their LDL,” Ridker said. “But the real question is what are we going to do in the future if this new biology says it’s all about inflammation?”

Cue the ZEUS trial—an ongoing, global, clinical assessment of IL-6 ligand inhibitor ziltevekimab for lowering atherosclerotic inflammatory biomarkers. New trial specifically observing patients with CKD and atherosclerosis, and elevated CRP.

Ridker, the trial’s co-chair, detailed ZEUS’ continuation of promising phase 2 findings with ziltevekimab, and what more his team would like to understand regarding inflammatory risk biomarkers in patients with atherosclerosis and kidney disease.

The study, "Differential Impact Of Residual Inflammatory Risk And Residual Cholesterol Risk Among Atherosclerosis Patients With And Without Chronic Kidney Disease : Secondary Analysis Of The Cantos Trial," was presented at ACC 2022.

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