There are no prospective RCTs specifically designed for patients with mid-range EF (EF of 41-49%). All data we have at this time has come from post-hoc or subset analyses from other heart failure trials. That being said, evidence suggests that at the lower end of this spectrum (closer to 41%), patients may respond to therapies similarly as those with a reduced EF <40%. The trajectory of these patients also matters, and it is dynamic – some will progress over time to overt HFrEF, while others may improve their ejection fraction. Guidelines now recommend initiating SGLT2 inhibitors in patients with HFmrEF as a Class 2a recommendation. In patients who are currently or have previously been symptomatic, there is a Class 2b recommendation for the use of beta blockers, ARNI, ACE/ARB, and MRAs, particularly those at the lower end of the spectrum. This is an evolving pathology, but the evidence suggests we should be thinking about them differently than patients with HFpEF and and EF of 50% or greater.
References: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure