CANTOS: New Hope for High-Risk Atherosclerosis Patients With Severe CKD?

Interleukin-1β inhibition with canakinumab reduces major adverse cardiovascular event (MACE) rates among high-risk atherosclerosis patients with moderate to severe chronic kidney disease (CKD), according to results of an analysis from the CANTOS study presented by Paul M. Ridker, MD, MPH, FACC, at ACC.18 in Orlando, FL.

The study was based on 10,061 patients with stable coronary artery disease post myocardial infarction (MI) from 39 countries between April 2011 and June 2017. Each patient was randomized to receive canakinumab subcutaneously every three months at a dose of 50 mg, 150 mg or 300 mg or to placebo.

The primary endpoint was major adverse cardiac events (MACE), including nonfatal MI, nonfatal stroke or cardiovascular death. The secondary endpoint was MACE plus unstable angina requiring urgent revascularization (MACE Plus). Patients were excluded if they had nephrotic syndrome or an estimated glomerular filtration rate less than 30ml/min/1.73m2.

Trial investigators noted that among CANTOS CKD patients, the largest benefits of canakinumab accrued among those who had the most robust anti-inflammatory response. Results showed those who achieved on-treatment hsCRP levels <2 mg/L after the first dose of canakinumab had a 31 percent reduction in MACE. No clinically meaningful benefits nor substantive harms with respect to adverse clinical renal events were seen with canakinumab.

"Canakinumab, an IL-1β inhibitor, represents a new class of therapy for atherosclerotic disease that lowers hsCRP and IL-6 with no effect on lipid levels and no hemodynamic effects," said investigators. "The current data demonstrate that anti-inflammatory therapy – at least with canakinumab – has considerable cardiovascular efficacy in high risk patients with moderate to severe CKD."

Looking ahead, the investigators suggest it will be important to extend these data and test the efficacy of canakinumab in patients with end-stage renal failure and/or those undergoing dialysis. "In that setting, hsCRP and IL-6 are powerful predictors of risk while LDL-C is not, and dialysis is one of the few settings where LDL reduction with statins has not been highly effective," they said. They recommend a new clinical trial of canakinumab in patients with severe renal failure recently initiating hemodialysis – an area where there is considerable unmet need.

Keywords: ACC18, ACC Annual Scientific Session, Primary Prevention, Inflammasomes, Creatinine, Interleukin-1, Research Personnel, Antibodies, Monoclonal, Renal Insufficiency, Chronic, Proteinuria, Thrombosis, Myocardial Infarction, Stroke, Inflammation, Hospitalization, Albumins

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