Anti-inflammatory therapy with canakinumab was found to reduce the total number of cardiovascular events in patients with prior myocardial infarction and evidence of residual inflammatory risk, according to a published study in the Journal of the American College of Cardiology.

A total of 10,061 patients with a prior history of myocardial infarction and a high-sensitivity C-reactive protein (hsCRP) levels ≥2 mg/L were enrolled in the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS; ClinicalTrials.gov Identifier: NCT01327846). Participants were randomly assigned to received placebo or the interleukin (IL)-1β inhibitor canakinumab at 50 mg, 150 mg, or 300 mg once every 3 months. The study’s primary endpoint was a composite of all serious cardiovascular events (myocardial infarction, stroke, coronary revascularization, and cardiovascular death).

During a median of 3.7 years of follow-up, 3417 serious cardiovascular events occurred in 2003 participants. Of participants who survived their first serious cardiovascular event, 73% had at ≥1 additional treatment.

Canakinumab reduced the rates of total serious cardiovascular events, with rates per 100 person-years in the placebo, 50-mg, 150-mg, and 300-mg canakinumab groups of 10.4, 8.4, 8.3, and 8.2, respectively. The corresponding rate ratios compared with placebo were: 0.80 (95% CI, 0.69-0.93) for 50 mg canakinumab, 0.79 (95% CI, 0.68-0.92) for 150 mg canakinumab, and 0.78 (95% CI, 0.67-0.91) for 300 mg canakinumab.


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“This study made the novel observation that canakinumab produced benefits on the total number of serious cardiovascular events regardless of whether patients receiving active therapy achieved reductions in hsCRP to <2 mg/L or reductions in IL-6 to <1.65 ng/L after adjusting for potential confounders,” noted the investigators.

Study limitations include the use of first-event analysis rather than of all serious cardiovascular events which would provide a more accurate assessment of the health burden caused by cardiovascular disease

“This analysis of the total burden of serious cardiovascular events in patients randomized in the CANTOS trial demonstrates that therapy with canakinumab leads to significant reductions in the rates of serious cardiovascular events in men and women with prior myocardial infarction and evidence of residual inflammatory risk,” concluded the study authors. “These reductions were observed among all participants who were allocated to IL-1β inhibition with canakinumab, including among those randomized to the lowest dose, and were sustained throughout the trial. In the appropriate patient population, IL-1β inhibition may offer the opportunity to reduce the burden of cardiovascular events experienced by high-risk patients.”

Reference

Everett BM, MacFadyen JG, Thuren T, et al. Inhibition of interleukin-1β and reduction in atherothrombotic cardiovascular events in the CANTOS trial. J Am Coll Cardiol. 2020;76:1660-1670.