Clinical Question

Do sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve cardiovascular outcomes in patients who have heart failure with preserved ejection fraction (HFpEF)?

Evidence-Based Answer

SGLT-2 inhibitors can reduce hospitalizations from heart failure but do not significantly reduce cardiovascular-related mortality. (Strength of Recommendation [SOR]: A, based on three meta-analyses of seven randomized controlled trials [RCTs] and one high-quality RCT.) Dapagliflozin (Farxiga) decreases symptoms of heart failure and improves distance walked in a six-minute walk test (mean increase = 8.3%). (SOR: B, based on one good-quality RCT.)

Evidence Summary

A 2020 systematic review and meta-analysis included two RCTs and a pooled analysis of two additional RCTs evaluating the effect of SGLT-2 inhibitors compared with placebo in patients who had heart failure with reduced ejection fraction and HFpEF.¹ The authors performed subgroup analyses of patients with preserved ejection fraction (n = 2,554). Patients (average age = 64 to 70 years) with diabetes mellitus and an ejection fraction greater than 45% were randomized to treatment with ertugliflozin (Steglatro), 5 or 15 mg per day; dapagliflozin, 10 mg per day; sotagliflozin (Zynquista; not available in the United States), 200 or 400 mg per day; or placebo with a follow-up of nine to 50 months. The primary outcome, a composite of hospitalization for heart failure and cardiovascular mortality, was not significantly different between the SGLT-2 inhibitors and placebo (four studies; n = 2,554; hazard ratio [HR] = 0.80; 95% CI, 0.63 to 1.00; P = .05). The SGLT-2 inhibitors did reduce the first hospitalization from heart failure (two studies; n = 1,815; HR = 0.71; 95% CI, 0.52 to 0.97; P = .03) but did not decrease cardiovascular mortality (two studies; n = 1,815; HR = 1.27; 95% CI, 0.92 to 1.76; P = .15). The validity of the primary outcome was limited by significant heterogeneity (I² = 63.9%).