Meta-Analysis Indicates SGLT2 Inhibitors Optimal for Heart Failure Treatment

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SGLT2 inhibitors, ARNIs, and MRAs were associated with a significant decrease in hospital admission for heart failure.

Consistent with guideline recommendations, a recent meta-analysis indicated that sodium-glucose cotransporter 2 (SGLT2) inhibitors were the optimal drug class for treatment of heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF).

Both SGLT2 inhibitors, as well as angiotensin receptor-neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs), were associated with a significant reduction in the risk of HF admission compared with placebo in the patient population.

However, no included drug classes were significantly associated with a reduced risk of death.

“The results of the sensitivity analysis showed that the incremental use of the included drug classes was probably associated with a progressive decrease in the risk of HF hospitalization among patients with HF and an left ventricular ejection fraction of 40% or more,” wrote study author Xiang Zhou, PhD, Department of Cardiology, The Second Affiliated Hospital of Soochow University.

Large-scale clinical trials on medical therapy for HF with higher ejection fraction have been neutral on the primary composite of death or hospitalization, but guidelines continue to recommend due to marginal benefits observed. Recently, SGLT2 inhibitors have been recommended for the patient population in guidelines due to positive findings in a large clinical trial.

However, no head-to-head studies have compared SGLT2 inhibitors with other HF drug classes. This bayesian network meta-analysis aimed to compare the outcomes, including all-cause death, cardiovascular death, and first hospital admission, associated with different drug combinations for the treatment of HFpEF and HFmrEF.

Investigators performed a search of PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) database published from inception to October 2021. The analysis then included randomized clinical trials with follow-up of more than 3 months of adult patients with symptomatic HF and LVEF of 40% or more. It assessed interventions including ARNIs, MRAs, ACE inhibitors. ARBs, SGLT2 inhibitors, and β-blockers.

A total of 19 randomized clinical trials with over 20,000 patients with HF and an ejection fraction of 40% or more without significant risk of bias were included after screening. Population characteristics, including age, sex, obesity degree, hemodynamics, and LVEF, were considered similar across the 7 different intervention classes.

In comparison to placebo, no treatments were associated with a significant reduction in the risk of all-cause death or cardiovascular death.

Still, investigators observed SGLT2 inhibitors, ARNIs, and MRAs all had significant associations with a decreased risk of hospital admission for HF compared with placebo.

  • SGLT2 inhibitors: HR, 0.71 (95% CrI, 0.60 - 0.83)
  • ARNIs: HR, 0.76 (95% CrI, 0.61 - 0.95)
  • MRAs: HR, 0.83 (95% CrI, 0.69 - 0.99)

They noted that SGLT2 inhibitors were the most optimal drug class in terms of reducing the risk for HF admission, followed by ARNIs and MRAs.

In sensitivity analysis, no intervention was associated with a significant reduction in all-cause death or HF hospitalization, but the probability that therapy was associated with greater decrease than placebo increased gradually with the incremental use of drug classes.

The study, “Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction A Meta-analysis,” was published in JAMA Network Open.