The EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials have significant implications in the United States, where the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors has increased by more than 40% in patients with heart failure (HF) and left ventricular ejection fraction (LVEF).  The goal of this study was to determine the population-level effect of lowering worsening HF episodes with SGLT-2 inhibitors in people with LVEF greater than 40% in the United States. Using an analytic decision model, researchers mapped newly eligible LVEF distributions from the Get With The Guidelines-Heart Failure registry onto self-reported HF data from the National Health and Nutrition Examination Survey between 2015 and 2018.

For the National Health and Nutrition Examination Survey, patients over 18 who were diagnosed with HF were split into 2 groups, according to their LVEF: those with an LVEF of 40% or more and those with an LVEF between 30% and 40%. From the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction), EMPEROR-Preserved, DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), and DELIVER trials, we estimated the number of patients who would need to be treated over a 3-year period to prevent one adverse event. The number of persons with HF who could benefit from SGLT-2 inhibitors is estimated to be 4,794,524 (95% CI, 3,997,363-5 591,684). It is estimated that 2,619,248 (95% CI, 2,183,759,3,054,737) of these people are newly eligible because their LVEF is greater than 40%. A total of 624,247 (95% CI, 520,457-728,037) to 627,124 (95% CI, 522,855-731,392) worsening HF events could be prevented across the LVEF spectrum with SGLT-2 inhibitors over 3 years, with 232 589 (95% CI, 193 918-271,260) to 282,879 (95% CI, 235,846-329,912) events prevented in individuals with LVEF greater than 40%.

Overall, the number of HF hospitalizations that could be avoided is estimated to range from 468,904 (95% CI, 390,942-546,867) to 499,110 (95% CI, 416,125-582,094); of this number, estimated 172,870 (95% CI, 144,128-201,613) to 231 018 (95% CI, 192 608-269 428) would be avoided in people with an LVEF of 40% or higher. Optimal adoption of SGLT-2 inhibitor therapy for HF with LVEF greater than 40% has the potential to prevent/postpone an additional 250,000 worsening HF episodes over 3 years in the United States, in addition to the demonstrated benefit in HF with a LVEF of 40% or less.