Preventing Heart Failure Admission with Sodium-Glucose Cotransporter-2 Inhibitors versus Angiotensin Receptor-Neprilysin Inhibitor: A Target Trial Emulation Study

Little is known on the real-world comparative effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus angiotensin receptor-neprilysin inhibitor (ARNi) used for heart failure (HF) management. This study used South Korea’s nationwide claims data from 2015 to 2020 to construct a population-based cohort of new users of SGLT2is or ARNi. Individuals were followed from the first prescription date of SGLT2is or ARNi until outcome occurrence, treatment switch or discontinuation, death, or end of the study period. Within the 1:1 propensity score-matched cohort, we estimated hazard ratios (HR) with 95% confidence intervals (CI) for the risk of HF admission with SGLT2is compared with ARNi using proportional subdistribution hazards model of Fine and Gray. We identified 496 propensity-score matched patient-pairs of SGLT2is and ARNi; with a mean age of 72.5 years and a male representation of 57.6%. Incidence rate of HF admission was 27.3 and 35.6 per 100 person-years in SGLT2is and ARNi group. When comparing the risk of HF admission associated with SGLT2is group with ARNi group, HR was 0.71 (95% CI 0.48-1.04). Effect modifications were observed by history of hospitalization for HF (p-for-interaction=0.002) and by recent use of renin-angiotensin-system inhibitors (p-for-interaction= 0.005). With future studies using more recent data warranted to corroborate our study results, these preliminary findings support current guideline recommendations for HF management and further, suggest similar effectiveness between SGLT2is and ARNi in routine care settings.