CBS 2019
CBSMD教育中心
English

科学研究

科研文章

荐读文献

Effect of a Home-Based Wearable Continuous ECG Monitoring Patch on Detection of Undiagnosed Atrial Fibrillation The mSToPS Randomized Clinical Trial Select Drug-Drug Interactions With Direct Oral Anticoagulants Generalizing Intensive Blood Pressure Treatment to Adults With Diabetes Mellitus Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials 2019 ESC Guidelines for the management of patients with supraventricular tachycardia The Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC): Developed in collaboration with the Association for European Paediatric and Congenital Cardiology (AEPC)he management of patients with) Variation in Revascularization Practice and Outcomes in Asymptomatic Stable Ischemic Heart Disease Non-cardiac surgery in patients with coronary artery disease: risk evaluation and periprocedural management ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2019 Appropriate Use Criteria for Multimodality Imaging in the Assessment of Cardiac Structure and Function in Nonvalvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and the Society of Thoracic Surgeons A Novel Familial Cardiac Arrhythmia Syndrome with Widespread ST-Segment Depression Screening for Cardiovascular Disease Risk With Electrocardiography: US Preventive Services Task Force Recommendation Statement

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 .).