CBS 2019
CBSMD教育中心
English

科学研究

科研文章

荐读文献

Pathophysiology, diagnosis and new therapeutic approaches for ischemic mitral regurgitation Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis Transcatheter Interventions for Tricuspid Valve Disease: What to Do and Who to Do it On Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair: The Randomized MITHRAS Trial Venous and Arterial Thromboembolism in Patients With Cancer: JACC: CardioOncology State-of-the-Art Review Italian Society of Interventional Cardiology (GIse) Registry Of Transcatheter Treatment of Mitral Valve RegurgitaTiOn (GIOTTO): Impact of Valve Disease Etiology and Residual Mitral Regurgitation after MitraClip Implantation Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies The Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Artery Pressure Index: Association With All-Cause Mortality in Patients With Moderate or Severe Tricuspid Regurgitation Novel Transcatheter Mitral Valve Prosthesis for Patients With Severe Mitral Annular Calcification Five-Year Clinical Outcomes After Drug-Eluting Stent Implantation Following Rotational Atherectomy for Heavily Calcified Lesions

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


BACKGROUNDExperimental 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.


METHODSWe 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.

RESULTSAt 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).

CONCLUSIONSAntiinflammatory 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 .).