Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Angiogenic cytokines in induced sputum of patients with sarcoidosis

Angiogenic cytokines in induced sputum of patients with sarcoidosis FIREMAN E, GILBURD D, MARMOR S. Respirology 2008 Background and objective: Sarcoidosis is a systemic granulomatous disorder of unknown aetiology involving multiple organs and often associated with non-granulomatous microangiopathic lesions in various organs. Increased angiogenesis-inducing ability of activated alveolar macrophages was found in bronchoalveolar specimens from patients with pulmonary sarcoidosis and from patients with extrapulmonary involvement. In contrast, decreased levels of vascular endothelial growth factor (VEGF) were found in BAL fluid recovered from sarcoid-associated pulmonary fibrosis. This study evaluated whether sarcoidosis is associated with abnormalities of VEGF and IL-8 in induced sputum (IS) samples. Methods: Twenty-three sarcoid patients and 13 controls performed IS. CD4/CD8 T-cell subsets were measured, as were pulmonary function tests and VEGF and IL-8. Results: Sarcoid patients showed significantly higher mean %lymphocytes (P = 0.04), significantly higher mean CD4/CD8 ratio (P = 0.0001) and significantly lower VEGF levels (P = 0.03) than controls. Patients with stages III-IV sarcoidosis showed a lower level of VEGF compared with those with stages I-II sarcoidosis (P = 0.048). IL-8 was detected in 10/35 samples and positively correlated with % neutrophils (P = 0.054) and eosinophils (P = 0.045). VEGF immunohistochemical staining showed a mixed pattern of expression in the same tissue samples and was low in fibrotic tissue areas. Conclusion: VEGF in IS samples may reflect impairment in angiogenesis associated with the extent of sarcoid fibrosis and functional disorders