Physicians' Academy for Cardiovascular Education

Total burden of serious CV events reduced by IL-1β inhibition

Inhibition of Interleukin-1b and Reduction in Atherothrombotic Cardiovascular Events in the CANTOS Trial

Literature - Everett BM, MacFadyen JG, Thuren T, et al. - J Am Coll Cardiol 2020;76:1660–70,

Introduction and methods

In the primary analysis of the CANTOS trial, treatment with the interleukin IL-1β canakinumab reduced first MACE (major adverse CV event) in patients with prior myocardial infarction (MI) and evidence of subclinical inflammation [1]. More recently, the COLCOT trial showed reduction of the composite endpoint of nonfatal MI, nonfatal stroke, urgent hospitalization for angina leading to coronary revascularization, resuscitated cardiac arrest or CV death with the anti-inflammatory agent colchicine [2].

These trial evaluated reduction of first atherothrombotic events with anti-inflammatory therapies. However, approach of assessing first CV event often underestimates the burden of the disease on the patient and the health care system.

Patients in the CANTOS trial were followed for the total duration of the trial, and those with a trial endpoint were asked to remain on their treatment for the duration of the trial.

This analysis examined the effect of canakinumab compared to placebo on the total number of serious CV events, a composite of nonfatal MI, nonfatal stroke, coronary revascularization, and CV death.

The CANTOS trial enrolled 10,061 patients with a history of MI and hsCRP ≥ 2 mg/mL, who were randomized to canakinumab 50 mg, 150 mg, or 300 mg one every 3 months subcutaneously, or to placebo. HRs for the effect of canakinumab on primary endpoint ranged from 0.88 (0.78-0.99) for the 50 mg dose to 0.83 (0.73-0.93, P=0.002) for the 300 mg dose. For this analysis, all events were counted (clinical endpoint was total number of serious CV events). 8058 Patients experienced no serious CV events, 1093 a single serious CV event and 910 >1 serious adverse event. A total of 3417 serious CV events occurred, consisting of 2003 first events and 1414 subsequent events. Median follow-up was 3.7 years.

Main results


This analysis of the CANTOS trial demonstrated that IL-1β inhibition with canakinumab lowered total number of serious CV events compared to placebo in patients with prior MI and evidence of ongoing subclinical inflammation. These results indicate that canakinumab reduces the total burden of CV events experience by high-risk patients.


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