Ridker PM, Everett BM, Thuren T et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Aug 27 [Epub ahead of print].
Pablo Avanzas, Consultant in Interventional Cardiology, Hospital Universitario Central de Asturias
CANTOS was designed to test directly the inflammatory hypothesis of atherothrombosis. In this trial, in patients with a history of myocardial infarction, the levels of high-sensitivity C-reactive protein and interleukin-6 were significantly reduced from baseline by canakinumab, as compared with placebo, with no significant reduction in lipid levels from baseline. Although the 50-mg dose of canakinumab did not have a significant effect on the primary cardiovascular end point as compared with placebo, patients in the 150-mg group had a risk of the primary end point that was 15% lower than the risk in the placebo group (3.86 vs. 4.50 events per 100 person-years) and a risk of the key secondary cardiovascular end point that was 17% lower than that in the placebo group (4.29 vs. 5.13 events per 100 person-years).
Although the patients in CANTOS had well-controlled levels of LDL cholesterol, rates of both the primary end point and the secondary cardiovascular end point in the placebo group were high, with cumulative incidences of more than 20% at 5 years. These data thus affirm that statin-treated patients with residual inflammatory risk as assessed by means of a high-sensitivity C-reactive protein level of 2 mg or more per liter at baseline have future event rates that are at least as high as, if not higher than, those among statin-treated patients with a residual risk due to LDL cholesterol level. The authors suggest that these two groups of patients may differ and may require personalized approaches to treatment.
The authors also found a significantly higher incidence of fatal infection and sepsis with canakinumab than with placebo, as well as a reduction in platelet counts with no increase in bleeding risk. By contrast, cancer mortality was significantly lower among patients assigned to receive canakinumab than among those in the placebo group. There was no significant difference between the canakinumab groups and the placebo group in all-cause mortality.
The findings of this proof of concept paper are of major importance as it opens a new avenue for the management of patients with ischaemic heart disease, namely addressing the inflammatory component of the disease. Whether, when and how these findings will translate into practical clinical recommendations is not known at this point in time. Undoubtedly, however, this study will represent a major paradigm change regarding the pathogenesis and treatment of IHD. The implications of the study in relation to the effects of canakinumab on cancer variables is also of potentially major clinical relevance.