Low-dose intravenous BNP with or without sildenafil did not improve estimated glomerular filtration rate (P=0.60) or blood urea nitrogen (P=0.38) compared to standard care in acute heart failure.
RCT (n=67)
Open-label
randomized
Does low-dose intravenous BNP alone or in combination with sildenafil improve renal function in patients hospitalized with acute heart failure and renal dysfunction?
Low-dose intravenous BNP, with or without sildenafil, successfully increases plasma cGMP but fails to improve renal function in patients with acute heart failure.
p-value: p=0.60 for eGFR, 0.38 for BUN
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00972569.
Hubers et al. (Fri,) conducted a rct in acute heart failure and renal dysfunction (n=67). low-dose intravenous BNP alone or with sildenafil vs. standard care was evaluated on percent change in estimated glomerular filtration rate and blood urea nitrogen from baseline to 48 hours (p=0.60 for eGFR, 0.38 for BUN). Low-dose intravenous BNP with or without sildenafil did not improve estimated glomerular filtration rate (P=0.60) or blood urea nitrogen (P=0.38) compared to standard care in acute heart failure.