Drug Therapy Combinations Could Reduce Hospitalization Among Heart Failure Patients with Higher Ejection Farction


The incremental use of drug combinations could prevent hospitalizations from heart failure among those who have higher ejection farction, a subgroup that struggles with insufficient data on treatments.

Researchers suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors are the most effective drug to lower the risk of hospitalization due to heart failure (HF) among patients who have preserved ejection fraction (HFpEF) and mildly reduced ejection farction (HFmrEF)—both of which have a left ventricular ejection fraction (LVEF) that is 40% or greater.

“The findings of this study suggest that SGLT2 inhibitors were the optimal drug class for HFpEF and HFmrEF, consistent with the most recent guideline recommendation,” the study authors wrote in their report, recently published in JAMA Open Network.

Heart failure affects 64 million people worldwide, causing severe associated morbidity and mortality risks. LVEF measures function of heart system, and based on this measurement, new guidelines have divided HF into 3 groups—HFmrEF, HFpEF, and HF with reduced ejection fraction (HFrEF). HF therapy has improved over the past 3 decades, particularly for HFrEF, which has a score of less than 39% on the LVEF.

Current US and European guidelines recommend treatment options such as SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRAs), angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and angiotensin receptor-neprilysin inhibitors (ARNIs), to treat HFrEF. However, medical therapy for the higher ejection fraction has not been proven to benefit patients yet.

Using a Bayesian network meta-analysis, researchers sought to compare outcomes of HF drugs among patients with HFmrEF or HFpEF. The researchers also wanted to understand whether the benefits were accumulated.

The team compared the outcome of these various treatment options against a placebo on 20,633 HF patients with at least a 40% ejection fraction from 19 randomized clinical trials (RCTs). The researchers followed up with patients after 3 months to evaluate the results.

Compared to the placebo group, the researchers found a significant reduction in hospitalizations due to HF with the drugs. However, no drug significantly reduced the risk of all-cause or cardiovascular death compared to the placebo.

“The probability that the therapy was associated with a greater decrease in HF hospitalization compared with placebo increased gradually with the increasing use of drug classes, reinforcing the viewpoint that the incremental benefits associated with treatment were not accidental,” the researchers wrote in the report.

This also indicates that HFmrEF and HFpEF patients with LVEF above 40% could benefit from these medical therapies similarly to people who have HFrEF, according to the study.

The investigators noted that the results of the RCTs cannot be translated among all HF patients because of internal selection biases. Additionally, few previous studies limited analyses on HFmrEF and HFpEF subgroups. Further, the study was limited because specific drug combinations were not studied.

“SGLT2 inhibitors were the optimal drug class. Our results are consistent with the latest guideline recommendations. If indicated, SGLT2 inhibitors may be preferentially recommended for patients with HFpEF or HFmrEF,” the study authors wrote in the report.


Xiang, Boyang,Zhang, Ruiqi, Wu, Xiaoguang, et al. Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction. September 20, 2022. JAMA Netw Open. 2022;5(9):e2231963. doi:10.1001/jamanetworkopen.2022.31963

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