CBS - The 17th Left Main & Coronary Bifurcation Summit, CBS2025

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Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis Right ventricular function and outcome in patients undergoing transcatheter aortic valve replacement Anticoagulation After Surgical or Transcatheter Bioprosthetic Aortic Valve Replacement Regurgitant Volume/Left Ventricular End-Diastolic Volume Ratio: Prognostic Value in Patients With Secondary Mitral Regurgitation Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation Association of White Matter Hyperintensities and Cardiovascular Disease: The Importance of Microcirculatory Disease 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Long-Term All-Cause and Cause-Specific Mortality in Asymptomatic Patients With CAC ≥1,000: Results From the CAC Consortium Prospective application of pre-defined intravascular ultrasound criteria for assessment of intermediate left main coronary artery lesions results from the multicenter LITRO study Impact of Staging Percutaneous Coronary Intervention in Left Main Artery Disease: Insights From the EXCEL Trial

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Clinical Trial2017 Sep 21;377(12):1119-1131.

JOURNAL：N Engl J Med. Article Link

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Ridker PM, Everett BM, CANTOS Trial Group et al. Keywords: Antiinflammatory Therapy; canakinumab; high-sensitivity C-reactive protein; therapeutic monoclonal antibody targeting interleukin-1β

ABSTRACT

BACKGROUND - Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.

METHODS - We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.

RESULTS - At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).

CONCLUSIONS - Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).

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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

ABSTRACT