Effect of nesiritide in patients with acute decompensated heart failure

Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.

Implications of serial measurements of natriuretic peptides in heart failure: insights from BIOSTAT‐CHF

No abstract available

Effects of adrenomedullin on angiotensin II stimulated atrial natriuretic peptide and arginine vasopressin secretion in healthy humans

Aims Adrenomedullin is a newly described peptide that has widespread tissue distribution. Its presence in cardiovascular (including vascular endothelial cells, smooth muscle cells, and cardiac atria and ventricles) and renal tissues, together with its vasodilatory and natriuretic properties, suggest a role in blood pressure regulation and fluid and electrolyte balance. Methods Nine normal volunteers were studied to determine whether or not adrenomedullin influenced plasma atrial natriuretic peptide and arginine vasopressin concentrations during systemic angiotensin II infusion. Results A significant (P = 0.02) augmentation of atrial natriuretic peptide concentrations, but no suppression of arginine vasopressin concentrations, was found with coinfusion of adrenomedullin and angiotensin II when compared with vehicle and angiotensin II. Conclusions Despite its vasodilator and natriuretic action, adrenomedullin significantly augmented angiotensin II-stimulated plasma atrial natriuretic peptide concentrations in healthy humans. This provides further evidence of a synergistic interaction between adrenomedullin and atrial natriuretic peptide and suggests that adrenomedullin may have a role in fluid and electrolyte balance and blood pressure regulation

Part-time medical practice: where is it headed?

One of the fundamental tenets of medicine has been the centrality of the profession as a life calling; physicians work long hours and routinely sacrifice personal interests for professional demands. In 1993, only 13% of clinical faculty and 6% of basic science faculty members of U.S. medical schools worked part-time.1 Historically, female physicians have been more likely than their male counterparts to work less than full time. Yet, despite increasing numbers of women in medicine and increased interest in personal time for self and family, U.S. medical workforce projections have forecast only a 3% decrease in the anticipated full-time equivalent of physicians over the next 10 years. (aut. ref.