Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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.

Inter-instrument reliability and agreement of fitbit charge measurements of heart rate and activity at rest, during the modified Canadian aerobic fitness test, and in recovery

© 2019, University of Toronto Press Inc.. All rights reserved. Purpose: We determined the inter-instrument reliability and agreement parameters of the Fitbit Charge Heart Rate (Charge HR) device during three phases: rest, modified Canadian Aerobic Fitness Test (mCAFT), and recovery. Method: We recruited 60 participants for this cross-sectional measurement study using convenience and snowball sampling approaches. The performance of the Charge HR was assessed throughout the rest, mCAFT, and recovery phases. To establish inter-instrument reliability, the Charge HR variables – heart rate, steps taken, and energy expenditures – were compared with those for two other devices: the Zephyr BioHarness (ZB) for heart rate and the Fitbit One for steps taken and energy expenditure. Measurements were recorded every 30 seconds. Results: At rest, the inter-instrument intra-class correlation coefficient (ICC) (standard error of measurement [SEM]) for the Charge HR versus the ZB was \u3e 0.97 (range, min–max, 1.02–1.32). During the mCAFT and in recovery, the ICCs (SEMs) for the Charge HR and the ZB were \u3e 0.89 (range, min–max, 1.30–3.98) and \u3e 0.68 (range, min–max, 3.58–8.35), respectively. During the mCAFT only, the number of steps taken and the energy expenditure recorded by the Charge HR and the Fitbit One displayed ICCs (SEMs) of 0.97 (83.00) and 0.77 (14.70), respectively. The average agreement differences in heart rate in this pair-wise device comparison indicated mean differences of –0.20, 4.00, and 1.00 beats per minute at rest, during the mCAFT, and in recovery, respectively. Conclusions: The Charge HR heart rate variable demonstrated excellent inter-instrument reliability compared with the ZB and provided good levels of agreement. The steps taken and energy expenditure variables displayed excellent reliability measures between Charge HR and Fitbit One. Our findings may be used to capture field-based wireless measures of heart rate in various phases and provide information about possibly using the Charge HR and ZB devices interchangeably