Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction A Meta-analysis

By Dr. Vinayak S Hiremath, MD, MRCP(Endocrinology & Diabetes), KMK Hospital Cochin,

Heart Failure (HF) affects 64 million people around the world, and it is a major cause of death and disability. Based on the left ventricular ejection fraction (LVEF), new guidelines divide HF into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). 


Since the 1980s, drug therapy for HFrEF has been getting better. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) were all linked to a lower risk of HF hospitalisation than placebo.


The results of this study suggest that using combinations of SGLT2 inhibitors, angiotensin-converting enzyme inhibitors–angiotensin receptor blockers, and -blockers led to benefits in HF hospitalisation rather than all-cause death among patients with HFpEF and HFmrEF. 


A previous network meta-analysis showed that ARNIs and angiotensin-converting enzyme (ACE) inhibitors were linked to a significant decrease in the risk of hospitalisation for HF in patients with HF and an LVEF of 40% or more, but MRAs were not. 


To learn more about this treatment, SGLT2 inhibitors need to be tested on more people with HFpEF or HFmrEF who are also taking MRAs and ARNIs. This network meta-analysis found that none of the drug classes were significantly linked to a lower risk of death for people with HFpEF or HFmrEF. But SGLT2 inhibitors, ARNIs, and MRAs were linked to a much lower risk of HF admission.


Based on the results of this study, sodium-glucose cotransporter 2 inhibitors seem to be the best class of drugs for HF with preserved ejection fraction and HF with mildly reduced ejection fraction.  This is in line with what the most recent guidelines suggest.


Reference: Boyang Xiang, Ruiqi Zhang, Xiaoguang Wu, et al. 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


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