Renal Effects of Combination Phosphodiesterase V Inhibition and Low-Dose B-Type Natriuretic Peptide in Acute Heart Failure: A Randomized Clinical Trial.

Abstract

Cardiorenal dysfunction with impaired cyclic GMP (cGMP) response is common in patients presenting with acute heart failure (HF). Type V phosphodiesterase (PDEV) is known to be upregulated in HF and may explain the dysfunction of renal response. The aim of this study was to determine whether B-type natriuretic peptide (BNP) alone or in combination with PDEV inhibition improves renal function and increases urinary sodium and cGMP excretion in acute HF. This open-label study included 67 patients hospitalized with acute HF and renal dysfunction. Patients were randomized to standard care, low-dose intravenous BNP (0.005 µg/kg per minute), or combination BNP/PDEV inhibition with sildenafil (25 mg q12 hours) for 48 hours. The coprimary end points were the percent change in estimated glomerular filtration rate and blood urea nitrogen from baseline to 48 hours. Treatment with BNP and BNP/PDEV inhibitor significantly increased plasma cGMP at 24 hours (+25.6% [+9.8%, +84.7%] and +60.8% [+32.3%, +103.8%] for BNP and BNP/PDEV versus -13.5% [-29.1%, +14.2%] with standard care; P=0.001). However, there was no significant change in estimated glomerular filtration rate 0 (-10.8%, +12.7%) for standard care versus 0 (-15.3%, +11.8%) for the BNP group versus -8.8% (-14.3%, +8.3%) for the BNP/PDEV group (P=0.60) or blood urea nitrogen -1.4% (-10.7%, +12.0%) for standard care versus -5.9% (-14.6%, +9.4%) for the BNP group versus +6.9% (-5.3%, +18.8%) for the BNP/PDEV group (P=0.38) between groups. Hypotension was more common in the BNP/PDEV inhibitor group. BNP and combination BNP/PDEV inhibition increased plasma cGMP in patients with acute HF but did not improve renal function or urinary sodium/cGMP excretion. Our study does not support the use of intravenous low-dose BNP with or without PDEV inhibition to enhance renal function in patients admitted with acute HF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00972569.