Eplerenone in patients with systolic heart failure and mild symptoms: analysis of repeat hospitalizations

Background—Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with heart failure and mild symptoms. In chronic diseases such as heart failure, characterized by repeat hospitalizations, analyzing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits. Methods and Results—The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (interquartile range, 1.08–3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient-years, respectively. Allowing for skewness in the frequency of hospitalizations by using the negative binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval, 0.42–0.66; P<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made a negligible difference in these findings. Conclusions—Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with heart failure and mild symptoms to a greater extent than is captured by only studying the time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects

Vascular and neuronal development: Intersecting parallelisms and rossroads

Two key events during evolution allowed vertebrates to develop specialized tissues able to perform complex tasks: the formation of a highly branched vascular system ensuring that all tissues receive adequate blood supply, and the development of a nervous system in which nerves branches to transmit electrical signal to peripheral organs. Both networks are laid down in a complex and stereotyped manner, which is tightly controlled by a series of shared developmental cues. Vessels and nerves use similar signals and principles to grow, differentiate and navigate toward their final targets. Moreover, the vascular and the nervous system cross-talk and, when deregulated, they contribute to medically relevant diseases. The emerging evidence that both systems share several molecular pathways not only provides an important link between vascular biology and neuroscience, but also promises to accelerate the discovery of new pathogenetic insights and therapeutic strategies