Canakinumab lowers CVD risk independent of lipid level
Anti-inflammatory injections lower the risk of cardiovascular disease in patients with previous myocardial infarction independently of lowering lipid levels, in a recent study reported in the New England Journal of Medicine.
The study randomised 10,061 patients with a previous history of MI to receive the anti-inflammatory monoclonal antibody canakinumab (50, 150 or 300 mg every 3 months) or placebo. Patients who received 150 mg of canakinumab had a 15% reduction in risk of subsequent cardiovascular events after 48 months of follow up compared to those who took a placebo (Table). The 150 mg dose met the pre-specified threshold for statistical significance. Lipid levels in treated patients did not reduce significantly from baseline, suggesting that the benefits of the drug in reducing cardiovascular disease risk occur independently of lipid-lowering action.
Interestingly, cancer mortality in patients who received canakinumab was also significantly lower than in patients who had the placebo. There were, however, significantly more deaths from infection or sepsis in the canakinumab group compared to the placebo, and no significant difference between the groups in deaths from any cause.
The study results provide further interesting evidence in the debate over the inflammatory hypothesis of atherothrombosis.Table: Summary of study results
|Canakinumab 50 mg||Canakinumab 150 mg||Canakinumab 300 mg|
|Mean reduction from baseline in CRP vs placebo||26%||37%||41%|
|Incidence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death * (events/100 person-years)||4.11||3.86||3.9|
|Hazard ratios (95% CI), p||0.93 (0.80, 1.07), 0.30||0.85 (0.74,0.98), 0.021||0.86 (0.75,0.99), 0.031|
CRP – high sensitivity C-reactive protein; * 3.7 years median follow-up (placebo group incidence rate 4.50 events/100 person-years)
Although this study is another confirmation of the importance of inflammation in atherosclerotic disease, further studies are required before this approach becomes a regular feature of clinical practice. However it opens up the idea of using inflammatory markers as a potential way of risk-stratifying patients.Ridker P, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. New Engl J Med 2017; 27 August: DOI: 10.1056/NEJMoa170791