Anti-IL1β Therapy Lowers Cardiovascular Risk after MI

Anti-inflammatory therapy with canakinumab—targeting the interleukin-1β (IL-1β) innate immunity pathway—reduces cardiovascular events in patients with previous myocardial infarction (MI), reports a trial in The New England Journal of Medicine.

The industry-sponsored “Canakinumab Antiinflammatory Thrombosis Outcome Study” (CANTOS) enrolled 10,061 adults with a history of MI. All had a persistent proinflammatory response, with high-sensitivity C-reactive protein of 2 mg/L or higher. Patients were randomly assigned to receive canakinumab every 3 months, 50, 150, or 300 mg sc; or placebo. Rates of nonfatal MI or stroke or cardiovascular death were compared between groups.

All three canakinumab doses reduced high-sensitivity C-reactive protein, with no effect on lipid levels. Primary outcome incidence rates at 3.7 years of follow-up were 4.50 events per 100 person-years in the placebo group, 4.11 events with canakinumab 50 mg, 3.86 events with the 150 mg dose, and 3.90 events with the 300 mg dose. Hazard ratios compared to placebo were 0.80 (not significant), 0.85, and 0.86, respectively.

A prespecified analysis combined the primary outcome with a secondary endpoint of hospitalization for unstable angina leading to urgent revascularization. For the composite outcome, only canakinumab 150 mg was superior to placebo: hazard ratio 0.83. All-cause mortality was not significantly different for canakinumab versus placebo. Rates of neutropenia and death from infections or sepsis were higher with canakinumab.

This clinical trial supports the hypothesis that treatment to reduce inflammation but not lipid levels can reduce cardiovascular events in patients with previous MI. Other approaches to anti-inflammatory therapy might also be effective in lowering cardiovascular risks. Anti-IL1β therapy with canakinumab is associated with an increased risk of serious infections and sepsis [Ridker PM, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; DOI: 10.1056/NEJMoa1707914].

October/November 2017 (Vol. 9, Number 10 & 11)