Optimal implementation of sodium-glucose cotransporter-2 inhibitors in US patients with heart failure estimated to cause a significant reduction in worsening heart failure events over 3 years

1. In this decision analytical model study among 4.8 million adults with heart failure in the United States, optimal implementation of sodium-glucose cotransporter-2 (SGLT-2) inhibitors over 3 years was estimated to prevent or postpone 630 000 worsening heart failure events across the left ventricular ejection fraction (LVEF) spectrum, of which approximately 230 000 to 280 000 preventable events were in patients with an LVEF greater than 40%.

2. An estimated 468 904 to 499 110 total heart failure hospitalizations could be prevented across the LVEF spectrum, of which 172 870 to 231 018 could be prevented in individuals with an LVEF greater than 40%.

Evidence Rating Level: 2 (Good)

Study Rundown: THE EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) and the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials have had major implications in the United States and have expanded the use of sodium-glucose cotransport-2 (SGLT-2) inhibitors in patients with heart failure (HF). The objective of this study was to estimate the potential US-population level implications of SGLT-2 inhibitor therapy in patients with HF by performing a decision analytical model study of all participants included in the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, and DELIVER trials. A secondary objective was to assess the benefit of SGLT-2 inhibitor therapy in patients with HF and LVEF greater than 40%. The main outcomes were worsening HF events, including unplanned HF hospitalizations, urgent HF visits requiring intravenous therapy, or cardiovascular death. A total of 4 794 524 adults with HF were eligible for SGLT-2 inhibitors, of which 2 619 248 were estimated as newly eligible with LVEF greater than 40%. Based on estimates from the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, and DELIVER trials, 624 247 worsening HF events were projected to be prevented across the LVEF spectrum with SGLT-2 inhibitor therapy over 3 years, of which 232 589 to 282 879 events were deemed preventable in individuals with LVEF greater than 40%. Furthermore, an estimated 468 904 to 499 110 total hospitalizations could be prevented across the LVEF spectrum, of which 172 870 to 231 018 could be prevented in individuals with an LVEF greater than 40%. A major strength of this study was its considerably large sample size. A limitation, however, was that the projected estimates neglect to consider adherence patterns, medication costs and potential perceived or true adverse reactions leading to drug discontinuation while on SGLT-2 inhibitor therapy for HF.

Click to read the study in JAMA Cardiology

Relevant Reading: SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: A systematic review and meta-analysis

In-Depth [retrospective cohort]: This study quantified the estimated US population-level implications of reducing worsening HF events with SGLT-2 inhibitor therapy in individuals with an LVEF greater than 40%. A projected total of 4 794 524 (95% CI, 3 997 363-5 591 684) adults (57% male; mean age, 66 years) with HF were eligible for SGLT-2 inhibitors, of which 2 619 248 (95% CI, 2 183, 759-3 054 737) were estimated as newly eligible with LVEF greater than 40%. The National Health and Nutritional Examination Survey (NHANES) was used to estimate the weighted prevalence of patients with HF in the US. Numbers needed to treat estimations over a period of 3 years were obtained for outcome measures from the following trials: EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, and DELIVER. Based on estimates from these trials, a projected 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, of which 232 589 (95% CI, 193 918-271 260) to 282 879 (95% CI, 235 846-329 912) events were deemed preventable in individuals with LVEF greater than 40%. Furthermore, an estimated 468 904 (95% CI, 390 942-546 867) to 499 110 (95% CI, 416 125-582 094) total hospitalizations could be prevented across the LVEF spectrum, of which 172 870 (95% CI, 144 128-201 613) to 231 018 (95% CI, 192 608-269 428) could be prevented in individuals with an LVEF greater than 40%. The numbers needed to treat (NNT) for 3 years of treatment for all efficacy endpoints were similar across the LVEF spectrum and ranged from 9 to13 for the composite endpoint of total HF hospitalizations and CV deaths and 10 to 16 for total HF hospitalizations.

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