Abstract
<title>Abstract</title> <p> <bold>Background</bold> Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases, and its prevalence continues to rise with population aging. However, evidence on recombinant human brain natriuretic peptide (rhBNP; nesiritide) for HFpEF has not been systematically synthesized. We therefore performed a systematic review and meta-analysis to evaluate the efficacy and safety of rhBNP in patients with HFpEF. <bold>Methods</bold> PubMed, Europe PMC, ClinicalTrials.gov, CNKI, Wanfang and VIP databases were searched on August 10, 2026 without language restrictions. Controlled clinical studies of intravenous nesiritide/rhBNP in adult patients with HFpEF or diastolic heart failure were included. Odds ratios (OR) and mean differences (MD) or standardized mean differences (SMD) were pooled using DerSimonian-Laird random-effects models, followed by leave-one-out sensitivity analyses. Risk of bias was assessed with the Cochrane RoB 2 tool or the Newcastle-Ottawa Scale. <bold>Results</bold> Of 82 deduplicated records, 7 studies with 1,314 patients were included (2 English, 5 Chinese). Compared with control, rhBNP significantly improved the overall clinical response rate (OR 2.97, 95% CI 1.40–6.28, I²=0%), left ventricular ejection fraction (MD 5.82%, 95% CI 4.07–7.57, I²=0%), E/A ratio (MD 0.27, 95% CI 0.21–0.33, I²=0%) and 6-minute walk distance (MD 26.56 m, 95% CI 12.98–40.13, I²=4.6%), and reduced NT-proBNP (SMD −2.49, 95% CI −4.29 to −0.69). No significant differences were found for death or heart failure rehospitalization (OR 0.79, 95% CI 0.22–2.82) or worsening renal function (OR 1.32, 95% CI 0.38–4.60), and sensitivity analyses indicated unstable results for these hard endpoints. No serious adverse events were reported; hypotension was more frequent with nesiritide in one study. <bold>Conclusions</bold> rhBNP may improve clinical efficacy, cardiac function and exercise capacity in HFpEF, whereas benefits on hard endpoints remain unproven. Given the predominance of small, short-term studies, large prospective randomized trials are warranted. </p>