SGLT2 inhibitors optimal for treating HF with preserved and mildly reduced ejection fraction: JAMA

The study, published in JAMA Network Open, further showed that the incremental use of the combination of SGLT2 inhibitors, β-blockers, and ACE inhibitors, or ARBs provided accumulative benefits in heart failure (HF) hospitalizations rather than all-cause mortality among HFmrEF and HFpEF patients.

Heart failure impacts about 64 million people globally, with considerable mortality and morbidity. Recent guidelines, based on the left ventricular ejection fraction (LVEF), classified HF into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF).

Pharmacologic therapy for HFrEF has continued to improve for 30 years. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), β-blockers, and angiotensin-converting enzyme (ACE) inhibitors have been recommended by the US and European clinical guidelines as disease-modifying treatments for HFrEF patients.

The increasing use of combinations of these drugs has contributed to progressive benefits for HFrEFpatients, but still, evidence for drug therapy for HFpEF and HFmrEF is insufficient. To fill this knowledge gap, Boyang Xiang, Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China, and colleagues aimed to compare the outcomes associated with different drug combinations for treating HFpEF and HFmrEF.

For this purpose, the researchers searched online databases for studies published from inception to October 9, 2021. Randomized controlled trials (RCTs) on ARBs, ACE inhibitors, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, SGLT2 inhibitors, and β-blockers for patients with HFpEF or HFmrEF. Primary outcomes included the first hospitalization for HF, cardiovascular, and all-cause mortality.

A total of 19 randomized clinical trials were included in the analysis, including 20 633 patients with HF and an ejection fraction of 40% or more, without a significant risk of bias.

The study's main findings were as follows:

• No treatments were associated with a significant reduction in the risk of all-cause death or cardiovascular death compared to placebo.
• SGLT2 inhibitors, MRAs, and ARNIs, were associated with a significant decrease in the risk of HF hospitalization compared with placebo (SGLT2 inhibitors: HR, 0.71; ARNIs: HR, 0.76; MRAs: HR, 0.83), and SGLT2 inhibitors were the optimal drug class in terms of reducing the risk for HF admission.
• Sensitivity analysis results demonstrated a progressive decrease in the risk of HF admission and an advance in mean rank associated with the increasing use of drug classes.

"Our findings are consistent with the latest guideline recommendations," the authors wrote. "If indicated, SGLT2 inhibitors should be preferred for patients with HFpEF or HFmrEF."

"The increasing use of combination therapies may be linked with accumulative benefits in terms of HF hospitalization than all-cause death for HF patients having an LVEF of 40% or more," they explained.

"There is a requirement for more research to explore the phenotypic classification and the LVEF cutoff for the effectiveness of drug therapies for patients with HFpEF or HFmrEF," the authors wrote in their conclusion.

Reference:

Xiang B, Zhang R, Wu X, Zhou X. Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction: A Meta-analysis. JAMA Netw Open. 2022;5(9):e2231963. doi:10.1001/jamanetworkopen.2022.31963