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CANTOS

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

Clinical Question

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?

Bottom Line

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.

Major Points

Guidelines

As of the knowledge cutoff date, no guidelines have been updated to reflect the results of this trial.

Design

- 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

Population

- 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

Interventions

- Canakinumab: 50 mg, 150 mg, or 300 mg subcutaneous injection every 3 months
- Placebo: Subcutaneous injection every 3 months

Outcomes

- 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.

Criticisms

- 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.

Funding

- Funded by Novartis.