Modulation of novel cardiorenal and inflammatory biomarkers by intravenous nitroglycerin and nesiritide in acute decompensated heart failure: an exploratory study.

BACKGROUND: Modulation of novel cardiorenal and inflammatory markers may provide insight into the disease process and outcomes of patients with acute decompensated heart failure. METHODS AND RESULTS: In this open-labeled, prospective, randomized study, 89 patients received either nesiritide (NES) or nitroglycerin (NTG) infusion by standard protocol. The serum or plasma concentrations of cystatin-C and inflammatory markers (high-sensitivity C-reactive protein, tumor necrosis factor-α, transforming growth factor-ß1, and interleukin-6) were measured in 66 patients with acute decompensated heart failure at baseline and during drug infusion. Mean baseline values for demographics were not significantly different between NTG and NES groups; however, baseline inflammatory markers were elevated on admission. In NES compared with NTG groups, lower cystatin-C (1449 versus 2739 ng/mL, P<0.05) and IL-6 (25 versus 50 pg/mL, P<0.05) were observed. There were no significant differences in concentrations of high-sensitivity C-reactive protein, tumor necrosis factor-α, and transforming growth factor-ß1 between groups over time. CONCLUSIONS: The differential modulation effects of cystatin-C and interleukin-6 but not other inflammatory markers, in response to NES compared with NTG therapy, may provide important implications for vasodilator therapy. Further studies are warranted to confirm these findings. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842023.

Renal function and neurohormonal changes following intravenous infusions of nitroglycerin versus nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Rises in serum creatinine and efficacy have been reported as dose-related effects of nesiritide and nitroglycerin in acute decompensated heart failure (ADHF). However, no study has evaluated the comparative safety, efficacy, and biomarkers of optimally dosed nesiritide versus nitroglycerin in ADHF. METHODS AND RESULTS: Eighty-nine ADHF patients were prospectively randomized to receive either nesiritide (0.01 µg kg(-1) min(-1) ± bolus) or nitroglycerin (maximally tolerated doses by standard protocol). Blood urea nitrogen (BUN), and creatinine were obtained during 48 hours of intravenous infusion. B-Type natriuretic peptide (BNP) and N-terminal (NT) proBNP concentrations were measured during hospitalization. There were no significant differences in BUN, serum creatinine, creatinine clearance, or hospitalization and mortality. Although concentrations of BNP and NT-proBNP were significantly decreased over time, the comparative reductions between the 2 vasodilators were similar. CONCLUSIONS: Nesiritide and nitroglycerin produce similar hemodynamic effects, do not worsen markers of renal function, and produce significant, yet similar, reductions in neurohormones over time. Both nitroglycerin at maximally titrated doses and nesiritide at standard doses are safe and effective in patients with ADHF who require vasodilator therapy.