Pharmacotherapy considerations for patients with heart failure with mildly reduced ejection fraction (HFmrEF) are discussed in a recent review published in the Journal of Pharmacy Practice.

Approximately one-quarter of heart failure (HF) patients have HFmrEF. Although first mentioned in the literature in 2014, HFmrEF was only recently defined by the Universal Definition and Classification of Heart Failure (HF) as HF with a left ventricular ejection fraction between 41% and 49%.

Despite an increasing emphasis on HFmrEF over the past several years, there is a lack of authoritative guidance surrounding therapeutic approaches for these patients, leaving a large portion of HF patients without a standard evidence-based approach. Because of this, the study authors aimed to review the epidemiology and pathophysiology of HFmrEF, as well as create a resource outlining the management and treatment of this condition.

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Several key principles on managing HFmrEF were obtained using subgroup analyses and meta-analyses. Because HF patients frequently oscillate between HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HFmrEF, it is recommended that therapy for HFmrEF be tailored based on the previous HF state of the specific patient. “For those improving from HFrEF, emphasis may be placed on the continuation of [guideline-directed medical therapy]; however, those patients worsening to HFmrEF from HFpEF, the initiation of medications more often used in HFrEF may be warranted,” the authors noted.

The use of specific medications for the management of HFmrEF is limited to subgroup analyses of trials involving HFrEF and HFpEF patients. Based on several analyses, initial consideration should be given to renin angiotensin aldosterone system blocking agents (eg, angiotensin converting enzyme inhibitors, angiotensin receptor blockers), as well as evidence-based beta blockers (eg, metoprolol succinate, carvedilol, bisoprolol).

Diuretic therapy should also be considered for symptom management. If symptoms persist and additional medications can be tolerated, spironolactone, digoxin, sodium-glucose co-transporter-2 inhibitors (in patients with type 2 diabetes), and calcium channel blockers may be added.

Currently, no therapies have been specifically analyzed in patients with HFmrEF. “The inclusion of patients with HFmrEF in future randomized controlled trials will ultimately be needed to gain further insight into appropriate medication management and optimization in this population within the changing landscape of chronic HF management,” the authors concluded.


  1. Baker C, Perkins SL, Schoenborn E, Biondi NL, Bowers RD. Pharmacotherapy considerations in heart failure with mildly-reduced ejection fraction. Journal of Pharmacy Practice. Published online June 24, 2021. doi: 10.1177/08971900211027315

2. Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure.  Universal Definition and Classification of Heart Failure. Journal of Cardiac Failure. doi: 10.1016/j.cardfail.2021.01.022

This article originally appeared on MPR