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.

Efeitos de exercícios aquáticos sobre a aptidão cardiorrespiratória e a pressão arterial em hipertensas Effects of aquatic exercise on cardiorespiratory fitness and blood pressure in hypertensive women

O estudo visou avaliar a influência de um programa de exercícios aquáticos sobre a aptidão cardiorrespiratória e a pressão arterial em mulheres hipertensas. Dez hipertensas participaram do programa de exercícios aquáticos - aeróbicos, de fortalecimento, alongamento e relaxamento - duas vezes por semana durante 7 semanas, totalizando 14 sessões. Foram avaliadas pelo teste de esforço cardiorrespiratório antes e após o desenvolvimento do programa. A pressão arterial foi mensurada ao repouso e aos 10, 20 e 30 minutos após o exercício em cada sessão. As variáveis cardiorrespiratórias não apresentaram alterações significativas após o programa, tanto dos valores de limiar de anaerobiose quanto os do pico de esforço. As pressões arteriais sistólica, diastólica e média de repouso permaneceram estáveis no decorrer do programa. Entretanto, no período pós-exercício, os níveis da pressão arterial sistólica (PAS) e média (PAM) foram significativamente menores, quando comparados aos valores pré-exercício: houve redução média de 6,43 mmHg da PAS e 3,08 mmHg da PAM aos 30 minutos pós-exercício. Assim, o programa de exercícios aquáticos proposto não promove ganho aeróbico efetivo, mas os resultados sugerem que exercícios aquáticos como os propostos, em intensidade próxima ao limiar de anaerobiose, desencadeiam redução dos níveis de pressão arterial no período pós-exercício, em mulheres hipertensas.<br>The aim of this study was to assess the influence of an aquatic exercise program on cardiorespiratory fitness and blood pressure in hypertensive women. Ten hypertensive women took part in the study. The program consisted of aquatic aerobic, strengthening, and stretching exercises in intensity near the anaerobic threshold, besides relaxation, twice a week during 7 weeks, totalling 14 sessions. They were assessed by cardiorespiratory exercise testing before and after program development. Blood pressure was measured at rest before and at 10, 20, and 30 minutes after exercise, at the end of each session. After the hydrotherapy program, cardiorespiratory ranges did not show significant changes, neither at the anaerobic threshold nor at the effort peak. Systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure at rest remained stable all through the program. However, SBP and MBP levels at 30-minute rest after exercises, at the end of the program, were significantly lower when compared to pre-exercise ones: there was a mean 6,43 mmHg SBP decrease and a 3,08 mmHg MBP decrease. The hydrotherapy program thus did not promote effective aerobic increase, but results suggest that the proposed exercises, performed at near-anaerobic threshold, may reduce post-exercise SBP and MBP levels in hypertensive women