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.

Psychometric testing of the Norwegian version of the questionnaire Family Satisfaction in the Intensive Care Unit (FS-ICU-24)

Bjørg Dale,1 Gro Frivold2 1Centre for Caring Research, Southern Norway, University of Agder, Faculty of Health and Sport Sciences, Grimstad, Norway; 2University of Agder, Faculty of Health and Sport Sciences, Grimstad, Norway Introduction: The questionnaire, Family Satisfaction in the Intensive Care Unit (FS-ICU-24), was developed to assess relatives’ satisfaction with care and involvement in decision-making processes when a close family member stays in the ICU Aim: This study was aimed at describing the translation and exploring the psychometric properties of the Norwegian version of the questionnaire. Methods: The study design was a cross-sectional survey. After translating the questionnaire according to recommended procedures, 123 close relatives of patients, recently treated in ICU, responded to a mailed questionnaire including the FS-ICU-24-No. Item-to-total correlations and Cronbach’s alpha coefficient were assessed for estimating reliability and construct validity was assessed by the “known groups” technique and explorative factor analysis. Results: The Cronbach’s alpha coefficient of 0.96 and significant item-to-total correlations supported the homogeneity of the instrument. The construct validity was reflected in significant differences in median scores on the total scale and subscales between the group reporting lower degrees of satisfaction and the group reporting higher degrees of satisfaction. Two fixed factors with an eigenvalue >1, and an explained variance of 62.5%, emerged from the factor analysis. Conclusion: The FS-ICU-24-No showed promising psychometric properties regarding reliability in this study group, which may indicate that the instrument is suitable for assessing family members’ satisfaction with care and decision making in Norwegian ICU. Keywords: decision making, family satisfaction, intensive care, reliability, validit