Abstract

Beneficial effects of therapeutic drugs are controversial for heart failure with preserved ejection fraction (HFpEF). This meta-analysis aimed to evaluate and compare the interactive effects of different therapeutic drugs and placebo in patients with HFpEF. A comprehensive search was conducted using PubMed, Google Scholar, and Cochrane Central Register to identify related articles published before March 2021. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure (HF) hospitalization, and worsening HF events. A total of 14 randomized controlled trials, comprising 19,573 patients (intervention group, n = 9,954; control group, n = 9,619) were included in this network meta-analysis. All-cause mortality, cardiovascular mortality, and worsening HF events among therapeutic drugs and placebo with follow-up of 0.5–4 years were not found to be significantly correlated. The angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin-converting enzyme inhibitor (ACEI) significantly reduced the HF hospitalizations compared with placebo (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.60–0.87 and HR 0.64, 95% CI 0.43–0.96, respectively), without heterogeneity among studies. The ARNI was superior to angiotensin receptor blocker (ARB) in reducing HF hospitalizations (HR 0.80, 95% CI 0.71–0.91), and vericiguat 10 mg ranked worse than beta-blockers for reducing all-cause mortality in patients with HFpEF (HR 3.76, 95% CI 1.06–13.32). No therapeutic drugs can significantly reduce mortality, but the ARNI or ACEI is associated with the low risk of HF hospitalizations for patients with HFpEF. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021247034

Highlights

  • The angiotensin receptor neprilysin inhibitor (ARNI) was superior to angiotensin receptor blocker (ARB) in reducing heart failure (HF) hospitalizations (HR 0.80, 95% confidence intervals (CIs) 0.71–0.91), and vericiguat 10 mg ranked worse than beta-blockers for reducing all-cause mortality in patients with Heart failure with preserved ejection fraction (HFpEF) (HR 3.76, 95% CI 1.06–13.32)

  • Heart failure with preserved ejection fraction (HFpEF), referred to as diastolic heart failure, is a heterogeneous clinical syndrome defined by the presence of signs and symptoms of heart failure (HF) with normal left ventricular ejection fraction (LVEF)

  • A previous study compared the effects of propranolol against placebo on mortality in elderly patients with HFpEF, and the results showed low mortality, with less nonfatal myocardial infarction and higher LVEF in the propranolol group (Aronow et al, 1997)

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Summary

Introduction

Heart failure with preserved ejection fraction (HFpEF), referred to as diastolic heart failure, is a heterogeneous clinical syndrome defined by the presence of signs and symptoms of heart failure (HF) with normal left ventricular ejection fraction (LVEF) (typically considered as ≥50%). The HFpEF constitutes greater than 50% of all HF diagnoses and is associated with considerable morbidity and mortality (Redfield, 2017). A previous study compared the effects of propranolol against placebo on mortality in elderly patients with HFpEF, and the results showed low mortality, with less nonfatal myocardial infarction and higher LVEF in the propranolol group (Aronow et al, 1997). The PARAGON HF trial results showed that the use of ARNI in HFpEF did not result in a significantly lower rate of HF hospitalization and cardiovascular mortality. The PEP-CHF trial of perindopril and TOPCAT trial of spironolactone in patients with HFpEF showed a significantly lower rate of HF hospitalization in the perindopril and spironolactone groups (Cleland et al, 2006; Pitt et al, 2014)

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