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

Yaowang Lin; Zhigang Cai; Jie Yuan; Huadong Liu; Xinli Pang; Qiuling Chen; Xinzheng Tang; Qingshan Geng; Shaohong Dong

doi:10.1186/s12933-022-01679-2

November 8, 2022Cardiovascular DiabetologyOpen Access

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

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Why the study?

Optimal treatment strategies for patients with heart failure with preserved ejection fraction remain uncertain.

Do pharmacological treatments (ACEIs, ARNIs, SGLT2 inhibitors) reduce mortality and heart failure events in patients with HFpEF compared to placebo?

Structured PICO

Do pharmacological treatments (ACEIs, ARNIs, SGLT2 inhibitors) reduce mortality and heart failure events in patients with HFpEF compared to placebo?

P

Population

15 RCTs including 31,608 patients with heart failure with preserved ejection fraction (HFpEF)

I

Intervention

Pharmacological treatments including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors

C

Comparator

Placebo

O

Outcome

All-cause deathhard clinical

In patients with HFpEF, SGLT2 inhibitors, ARNIs, and ACEIs reduce HF hospitalizations, but only SGLT2 inhibitors reduce worsening HF events, with no therapies showing a mortality benefit.

Implication

Supports prioritizing SGLT2 inhibitors to reduce HF events in HFpEF; extends meta-analytic confirmation of benefit without mortality reduction.

Abstract

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.