SGLT-2 Inhibitor Use for Heart Failure With LVEF of More Than 40% May Reduce Worsening Events

In patients with heart failure and an LVEF of more than 40%, use of SGLT-2 inhibitors can reduce risk for worsening heart failure events over 3 years.

Optimal use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors for heart failure (HF) with left ventricular ejection fraction (LVEF) of greater than 40% can potentially prevent or postpone approximately an additional 250,000 worsening HF events for 3 years in the United States, according to a study published in JAMA Cardiology.

Investigators aimed to determine the potential US population-level effects of SGLT-2 inhibitor therapy in HF in a decision analytical model study of participants in the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, and DELIVER trials, as well as evaluate the benefit of additional SGLT-2 inhibitor therapy to patients with HF and an LVEF of greater than 40% for rates of worsening HF events.

Estimates of self-reported HF from 2015 to 2018 (n=19,255) were obtained from the National Health and Nutritional Examination Survey (NHANES). Data were collected from the American Heart Association Get With The Guidelines-Heart Failure (GWTG-HF) registry to identify LVEF distribution in patients aged 18 years and older who were hospitalized from January 1, 2014, to September 30, 2019, at 529 US hospitals.

The assessment of population-level impact was evaluated with the following endpoints, standardized for 1 and 3 years:

  • Total (first and recurrent) HF hospitalizations
  • Composite of total (first and recurrent) HF hospitalizations and cardiovascular (CV) deaths
  • Composite of worsening HF event (expanded composite including urgent HF visits and total HF hospitalizations) or CV death

Numbers needed to treat were computed for each CV endpoint according to patient-year observed with use of data at 1 and 3 years.

The projected decrease in HF-associated morbidity that could be achieved with optimal implementation of SGLT-2 inhibitors could substantially reduce the economic burden of HF events on the US health care system.

A total of 4,794,524 (95% CI, 3,997,363-5,591,684) patients with HF were identified (mean age, 66.4 [95% CI, 64.8-68.0] years; 56.5% men; 67.3% non-Hispanic White). An estimated 2,175,276 (45.3%) of patients with HF and an LVEF of 40% or less already would have achieved the LVEF criteria of the previous indication for SGLT-2 inhibitors. Expanded treatment eligibility to patients with HF and LVEF of greater than 40% led to an additional 2,619,248 (95% CI, 2,183,759-3,054,737) individuals who were eligible to receive SGLT-2 inhibitors.

Optimal administration of SGLT-2 inhibitor therapy for all LVEF values was estimated to prevent or postpone 499,110 (95% CI, 416,125-582,094) to 468,904 (95% CI, 390,942-546,867) total HF hospitalizations, 562,397 (95% CI, 468,890-655,905) to 591,165 (95% CI, 492,875-689,455) total HF hospitalizations and CV deaths, and 624,247 (95% CI, 520,457-728,037) to 627,124 (95% CI, 522,855-731,392) worsening HF events or CV deaths for 3 years.

Optimal use of SGLT-2 inhibitors in HF with LVEF of greater than 40% was estimated to prevent or delay 172,870 (95% CI, 144,128-201,613) to 231,018 (95% CI, 192,608-269,428) total HF hospitalizations, 202,730 (95% CI, 169,023-236,437) to 265,592 (95% CI, 221,433-309,750) total HF hospitalizations and CV deaths, and 232,589 (95% CI, 193,918-271,260) to 282,879 (95% CI, 235,846-329,912) worsening HF events or CV deaths for 3 years.

The 3-year numbers needed to harm for symptomatic hypotension and genital infections were 52 and 42, respectively. Optimal use of SGLT-2 inhibitors could result in an estimated 56,578 (95% CI, 47,170-65,985) patients having a symptomatic hypotension event and 64,434 (95% CI, 53,721-75,147) having a genital infection in 3 years.

Among several limitations, the projected estimates assume that patients will adhere to therapy for 3 years and do not account for adherence patterns, medication costs, and potential perceived or true adverse reactions causing drug discontinuation. Also, the projected HF population from the NHANES registry is a weighted mean of self-reported HF data and may not be a true estimate of HF prevalence, and heterogeneity occurred in the safety endpoint definition in the DAPA-HF and DELIVER trials.

“The projected decrease in HF-associated morbidity that could be achieved with optimal implementation of SGLT-2 inhibitors could substantially reduce the economic burden of HF events on the US health care system,” wrote the researchers.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.