OBJECTIVES:

Newer treatments, e.g., sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin-receptor-neprilysin inhibitors (ARNi), have emerging evidence showing efficacy in improving health outcomes for patients with heart failure with preserved ejection fraction (HFpEF). However, there is no consensus on the most effective treatment for HFpEF. Thus, we aim to evaluate the comparative efficacy of pharmacological treatments in patients with HFpEF.

METHODS:

We systematically searched MEDLINE, EMBASE, and CENTRAL until February 2022 for randomized controlled trials (RCTs) assessing the efficacy of pharmacologic treatments among adult patients with HFpEF (defined as left ventricular ejection fraction ≥45%). Study outcomes included (1) all-cause mortality, (2) cardiovascular death, (3) hospitalization for heart failure (HHF), and (4) a composite endpoint of the three. A random network meta-analysis using a frequentist framework model was employed to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI). Treatments were ranked using the surface under the cumulative ranking curve score (P-score).

RESULTS:

We identified 11 eligible RCTs, including 30,621 participants with HFpEF. For the risk of HHF, ARNi (P-score: 0.85; RR [95% CI]: 0.73 [0.61-0.87]) and SGLT2i (0.83; 0.74 [0.66-0.83]) were both effective treatments, followed by mineralocorticoid receptor antagonists (MRA) (0.61; 0.82 [0.67-1.00]). Results were similar for the composite outcome, and ARNi (0.85; 0.75 [0.64-0.87]) and SGLT2i were both effective (0.83; 0.80 [0.72-0.87]), followed by MRA (0.61; 0.89 [0.75-1.06]). None of the following four treatments investigated (beta-blockers, MRA, ARNi, and SGLT2i) showed significant benefits in lowering the risks of all-cause death or cardiovascular death.

CONCLUSIONS:

Among participants with HFpEF, ARNI and SGLT2i were the most effective treatments for reducing the risks of HHF and the composite end point of all-cause death, cardiovascular death, hospitalization, and HHF. None of the treatments significantly decreased the risk for all-cause death or cardiovascular death.