OBJECTIVES:

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are now recommended for the management of heart failure with preserved ejection fraction (HFpEF), but little is known about their in-class comparative effectiveness in real-world settings. To fill this knowledge gap, we assessed the comparative effectiveness of SGLT2i for preventing HF-related and all-cause hospitalizations among patients with HFpEF.

METHODS:

We conducted a retrospective cohort study of patients with diagnosed HFpEF who initiated SGLT2i using MarketScan® Commercial and Medicare Supplemental databases (2012–2020). Stabilized inverse probability treatment weighted Cox proportional hazards regression was used to compare HF-related and all-cause hospitalizations in three pairwise comparisons: dapagliflozin vs. canagliflozin; empagliflozin vs. canagliflozin; and dapagliflozin vs. empagliflozin. Subgroup and sensitivity analyses were conducted to assess robustness of the main analysis.

RESULTS:

3,629 new users with SGLT2i (881 dapagliflozin, 1,120 canagliflozin, and 1,628 empagliflozin) were identified. Compared with canagliflozin use, dapagliflozin use was associated with decreased risk of HF-related hospitalization (adjusted hazard ratio [aHR], 0.75; 95% confidence interval [CI], 0.56–1.01) and all-cause hospitalization (aHR, 0.84; 95% CI, 0.73–0.97). Compared with canagliflozin use, empagliflozin use was associated with 55% decreased risk of HF-related hospitalization (aHR, 0.45; 95% CI, 0.34–0.59) and 18% decreased risk of all-cause hospitalization (aHR, 0.82; 95% CI, 0.73–0.93). Compared with empagliflozin use, dapagliflozin use was associated with 50% increased risk of HF-related hospitalization (aHR, 1.50; 95% CI, 1.09–2.07) but no differences in the risk of all-cause hospitalization (aHR, 1.05; 95% CI, 0.92–1.20).

CONCLUSIONS:

Compared with canagliflozin or dapagliflozin use, empagliflozin use was associated with decreased risk of HF-related and all-cause hospitalizations. Compared with canagliflozin, dapagliflozin was associated with decreased risk of HF-related and all-cause hospitalizations.