Effect of pharmacological treatment on outcomes of heart failure with preserved ejection fraction: an updated systematic review and network meta-analysis of randomized controlled trials

BACKGROUND: Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF. METHODS: Randomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis. RESULTS: Fifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 − 0.96), OR = 0.73, (95%CI 0.61 − 0.86), and OR = 0.74, (95%CI 0.66 − 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 − 0.83)]. CONCLUSIONS: No treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01679-2.