OBJECTIVES: This research investigated the relative efficacy, using indirect treatment comparison (ITC) methodology, of empagliflozin with that of sacubitril/valsartan among patients with heart failure with reduced ejection fraction (HFrEF). Empagliflozin + standard of care (SoC) and sacubitril/valsartan + SoC were investigated in separate, Phase 3, randomized controlled trials (EMPEROR-REDUCED and PARADIGM-HF, respectively).

METHODS: In the absence of direct evidence, ITCs were conducted to estimate the relative efficacy of empagliflozin with sacubitril/valsartan. It was assumed that the placebo + SoC arm in EMPEROR-REDUCED was comparable to the enalapril + SoC arm in PARADIGM-HF. Bucher ITC methodology used this common comparator arm. The primary endpoint (time to first event of adjudicated cardiovascular [CV] death or adjudicated hospitalization for heart failure [HHF]) was compared. Time to adjudicated CV death and time to adjudicated HHF were also analyzed individually, alongside a further time to event endpoint: time to all-cause mortality. Subgroup analyses and anchored matching-adjusted indirect comparisons were performed as sensitivity analyses.

RESULTS: For the composite primary endpoint, both empagliflozin and sacubitril/valsartan showed significant and similar improvements over placebo. The Bucher ITC based hazard ratio (HR) (95% confidence interval [CI]) for this endpoint comparing empagliflozin with sacubitril/valsartan was 0.94 (0.79, 1.11). Overall, results suggested similar efficacy between empagliflozin and sacubitril/valsartan. The Bucher ITC HRs (95% CI) for time to adjudicated HHF, time to adjudicated CV death, and time to all-cause mortality were 0.87 (0.72, 1.06), 1.15 (0.91, 1.45) and 1.10 (0.89, 1.34), respectively. The sensitivity analyses produced results consistent with the Bucher ITCs.

CONCLUSIONS: This indirect comparison suggests patients with HFrEF who are treated with empagliflozin have similar efficacy across key outcomes in heart failure compared with sacubitril/valsartan treated patients.