Population-Level Implications of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Preserved Ejection Fraction in the US

Abstract

ImportanceThe expansion of sodium-glucose cotransporter-2 (SGLT-2) inhibitor use in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) more than 40% following 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 major implications in the US.ObjectiveTo quantify the estimated US population-level impact of reducing worsening HF events with SGLT-2 inhibitors in individuals with LVEF more than 40%.Design, Setting, and ParticipantsThis decision analytical model study used self-reported HF data from the National Health and Nutritional Examination Survey from 2015 to 2018, which was weighted across the entire US population and subsequently mapped onto newly eligible LVEF distributions from the Get With The Guidelines–Heart Failure registry. All patients older than 18 years with HF from the National Health and Nutritional Examination Survey were grouped into the following categories: all LVEF and LVEF more than 40%. Numbers needed to treat estimations over 3 years were obtained for outcome measures 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.Main Outcomes and MeasuresWorsening HF events (unplanned HF hospitalizations, urgent HF visits requiring intravenous therapy, or cardiovascular death).ResultsA projected 4 794 524 (95% CI, 3 997 363-5 591 684) adults (57% male; 67% White; mean age, 66 years) with HF would be eligible for SGLT-2 inhibitors. Of this total population, 2 619 248 (95% CI, 2 183 759-3 054 737) would be estimated as newly eligible with LVEF more than 40%. Based on estimates from the EMPEROR-Reduced/EMPEROR-Preserved and DAPA-HF/DELIVER 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 could be prevented in individuals with LVEF more than 40%. Moreover, an estimated 468 904 (95% CI, 390 942-546 867) to 499 110 (95% CI, 416 125-582 094) total HF 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 LVEF more than 40%.Conclusions and RelevanceIn addition to the proven benefit in HF with LVEF of 40% and less, optimal implementation of SGLT-2 inhibitor therapy for HF with LVEF more than 40% can potentially prevent/postpone an additional approximately 250 000 worsening HF events over 3 years in the US.

Modifiability of Composite Cardiovascular Risk Associated With Chronic Kidney Disease in Type 2 Diabetes With Finerenone

“…Therefore, HHF would likely account for a large proportion of the cardiovascular events prevented with finerenone at a population level as estimated in this analysis. Similar simulation analyses based on NHANES data estimated that in treatment-eligible patients with HF in the US, up to 250 000 and 180 000 worsening HF events could be prevented over 3 years of treatment by sodium-glucose cotransporter-2 inhibitors and sacubitril/valsartan, respectively . However, these did not specifically consider patients with CKD and T2D.…”

Potential global impact of sodium–glucose cotransporter‐2 inhibitors in heart failure

“…We designated the following endpoints for assessment of population-level impact, standardized over 1 and 3 years: (i) total (first and recurrent) HF hospitalizations, (ii) composite of total (first and recurrent) HF hospitalizations and CV deaths, and (iii) composite of worsening HF event (expanded composite inclusive of urgent HF visits and total HF hospitalizations) or CV death, as done in a prior similar study. 7 Urgent HF visits were defined as urgent outpatient or emergency room visits for worsening HF that required intravenous therapy. Event rates for these endpoints were obtained from the DAPA-HF and EMPEROR-Reduced trials for LVEF ≤40% and from the EMPEROR-Reduced and DELIVER trials for LVEF >40%.…”

“…were projected to be prevented over 3 years. 7 Global uptake of SGLT-2 inhibitors for HF would also lead to major patient and population-level benefits in the setting of a nearly two-fold increase in global HF cases from 1990 to 2017, 8 especially in low-and middle-income countries but represents a major challenge with regional variation in health system infrastructure, health policy, and access to healthcare. In this decision analytical model study, we sought to examine the potential global impact of optimal implementation of SGLT-2 inhibitor therapy in HF across the LVEF spectrum.…”

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

“…Dapagliflozin’s effect was evident as early as 2 weeks after initiation [ 158 ], was more pronounced in subjects with a worse baseline symptom burden [ 159 ], and was consistent irrespective of age, body mass index, frailty, baseline glycemic status, or MRA/ARNI use [ 160 , 161 , 162 , 163 , 164 ]. The expected addition of SGLT2i in the societal guidelines of HFpEF/HFmrEF management may result in a significant alleviation of HF burden, with a recent study indicating 250,000 fewer hospitalizations for worsening HF in this group of patients [ 165 ].…”