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

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are effective across the spectrum of left ventricular ejection fraction (LVEF) in heart failure (HF); however, population-wide medication use in eligible patients remains suboptimal. We evaluated the potential implications of optimal global implementation of SGLT-2 inhibitors in HF.

A decision analytical study was performed using the global prevalence of HF from the Global Burden of Disease 2017 report. Exclusion criteria were applied using the NHANES to ascertain an SGLT-2 inhibitor-eligible population, which was mapped onto global LVEF distributions from the REPORT-HF registry. The number needed to treat for 3 years for the composite of worsening HF events and cardiovascular deaths was calculated from estimated event rates in the DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and DELIVER trials and projected onto the eligible population. An estimated 49 329 000 (95% confidence interval [CI] 43 882 000-54 929 000) HF patients would be eligible for SGLT-2 inhibitors across all LVEFs, including 25 651 000 (95% CI 22 818 000-28 563 000) with LVEF ≤40% and 23 678 000 (95% CI 21 063 000-26 366 000) with LVEF >40%. Optimal implementation of SGLT-2 inhibitors would be projected to prevent/postpone 4 512 011 (95% CI 4 013 686-5 024 232) to 5 986 943 (95% CI 5 325 721-6 666 604) total worsening HF events and cardiovascular deaths over 3 years in patients with LVEF <40%. An additional 2 102 606 (95% CI 1 870 394-2 341 301) to 2 557 224 (95% CI 2 274 804-2 847 528) total worsening HF events and cardiovascular deaths would be prevented/postponed in patients with LVEF >40%. Among all eligible HF patients, irrespective of LVEF, 7 069 235 (95% CI 6 288 490-7 871 760) to 8 089 549 (95% CI 7 196 115-9 007 905) total worsening HF events and cardiovascular deaths would be prevented/postponed over this period.

Optimal implementation of SGLT-2 inhibitors globally in HF is projected to prevent/postpone approximately 7-8 million worsening HF events and cardiovascular deaths over 3 years.