"Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS)". The New England Journal of Medicine. 2017. 377(12):1119-1131. PubMed
Links to original sources: Wiki Journal Post Full Journal Article
Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading
Does canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, lead to a lower rate of recurrent cardiovascular events in patients with a previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter?
Canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events compared to placebo, independent of lipid-level lowering.
The CANTOS trial was designed to test the inflammatory hypothesis of atherothrombosis by evaluating the efficacy of canakinumab, an interleukin-1β blocker, in reducing recurrent cardiovascular events post-myocardial infarction in patients with elevated high-sensitivity C-reactive protein levels.
As of the knowledge cutoff date, no guidelines have been updated to reflect the results of this trial.
- Multicenter, double-blind, randomized, placebo-controlled trial - N=10,061 - Intervention: Three doses of canakinumab (50 mg, 150 mg, and 300 mg injected subcutaneously every 3 months) versus placebo - Setting: 27 centers - Enrollment: April 2011 to March 2014 - Mean follow-up: 3.7 years - Analysis: Intention-to-treat - Primary outcome: A composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death
- Inclusion Criteria: Patients with a history of myocardial infarction and high-sensitivity C-reactive protein levels ≥2 mg per liter - Exclusion Criteria: Chronic or recurrent infection, history of cancer except basal-cell skin carcinoma, immunocompromised state, high risk of tuberculosis, or on other systemic anti-inflammatory treatments - Baseline Characteristics: Mean age 61 years, 25.7% female, 40.0% with diabetes
- Canakinumab: 50 mg, 150 mg, or 300 mg subcutaneous injection every 3 months - Placebo: Subcutaneous injection every 3 months
- Primary Outcome: The 150-mg dose showed a significant reduction in the rate of the primary efficacy endpoint compared to placebo, with hazard ratios of 0.85 (P=0.021) for the primary endpoint and 0.83 (P=0.005) for the key secondary cardiovascular endpoint that additionally included hospitalization for unstable angina leading to urgent revascularization. - Secondary Outcomes: Canakinumab was associated with a higher incidence of fatal infections compared to placebo and did not significantly reduce all-cause mortality. There was no significant increase in the risk of neutropenia, thrombocytopenia, or hemorrhage. The cancer mortality rate was significantly lower among those receiving canakinumab.
- The trial showed a higher incidence of fatal infections with canakinumab use. - There was no significant difference in all-cause mortality, and only the 150 mg dose met the significance threshold for the primary endpoint.
- Funded by Novartis.
- The full article with additional details and results can be found at NEJM.org.