OBJECTIVES : The landmark Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial demonstrated the efficacy of dapagliflozin for the treatment of heart failure with reduced ejection fraction (HFrEF) when used in addition to standard therapy (ST). The objective of this study was to indirectly compare the efficacy of adding dapagliflozin to ST versus switching to sacubitril/valsartan for the treatment of HFrEF.

METHODS : Patient data from DAPA-HF and summary data from PARADIGM-HF were utilized to conduct a matching-adjusted indirect comparison. Matching variables were selected based on their treatment modifying effect in DAPA-HF and comparisons were anchored via the control arms of the trials. Primary analysis was conducted on the subgroup of DAPA-HF patients whose ST included an angiotensin converting enzyme inhibitor for consistency with the control arm of PARADIGM-HF who received enalapril. Sensitivity analysis was conducted for patients receiving angiotensin II receptor blockers (ARBs). The hazard ratio (HR) of dapagliflozin+ST versus sacubitril/valsartan was estimated for the composite and individual components of time to first hospitalization for HF (HHF) or cardiovascular (CV) death, and all-cause death.

RESULTS : The estimated HR of dapagliflozin+ST versus sacubitril/valsartan on the composite of time to HHF or CV death was 0.94 (95% confidence interval: 0.77-1.15) based on a naïve comparison between trials; after matching the estimated effect of dapagliflozin+ST versus sacubitril/valsartan increased to 0.91 (0.68-1.21). Similar results were observed for individual components of the composite and all-cause death after matching, with HRs of 0.93 (0.66 -1.32), 0.93 (0.63-1.36) and 0.92 (0.65-1.31) for time to HHF, CV death and all-cause death, respectively. Results were consistent for patients receiving ARBs as part of ST in DAPA-HF.

CONCLUSIONS : Based on an indirect comparison of the results of DAPA-HF and PARADIGM-HF, treatment with dapagliflozin+ST was nominally superior to sacubitril/valsartan for the treatment of HFrEF, however no statistically significant differences were observed between treatment groups.