(B52) Preventing Heart Failure Admissions with Sodium-Glucose Cotransporter-2 Inhibitors versus Angiotensin Receptor-Neprilysin Inhibitors: A Target Trial Emulation Study

Publication Number: 662

Background: Recent guidelines for heart failure (HF) management now recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i), in addition to conventional HF drugs (incl. angiotensin receptor-neprilysin inhibitors [ARNi]), as guideline-directed medical therapy. Yet, the direct, comparative effectiveness of SGLT2i versus ARNi remain unknown as existing data are limited to network meta-analysis of trials, which were also inconsistent.

Objectives: To assess the risk of HF admissions with SGLT2i vs. ARNi in real-world settings.

Methods: We emulated a hypothetical target trial using Korea’s nationwide claims data between 2015 and 2020 and an active comparator, new-user design. Individuals newly prescribed a SGLT2i or an ARNi in 2020 were eligible for cohort entry (first prescription date), given the publication of DAPA-HF trial results in 2019. The outcome of interest was first hospitalization for HF, with patients followed up from cohort entry until the earliest of outcome occurrence, switch to a comparator drug, treatment discontinuation (30-day grace period), death, or end of the study; as-treated approach. We matched 1:1 between SGLT2i and ARNi using propensity scores that accounted for 56 baseline covariates, and estimated the incidence rate of outcome per 100 person-years and HRs with 95% CIs using proportional subdistribution hazards model of Fine and Gray (death considered a competing event). We also conducted an intention-to-treat analysis that did not censor follow-up at treatment interruption. We considered CIs that did not overlap 1 as statistically significant.

Results: Of 12,868 new users of SGLT2i or ARNi, we identified 496 patient-pairs with a mean age of 73.1 (SGLT2i) and 72.0 years (ARNi). All baseline covariates, except for baseline use of β-blockers, achieved balance between groups after matching (absolute standardized differences < 0.1). In the matched cohort, the rate of HF admission was lower with SGLT2i than ARNi (27.3 vs. 35.6 per 100 person-years), corresponding to a HR of 0.71 (95% CI 0.48-1.04); intention-to-treat analysis was consistent (0.71, 0.49-1.02). Results of subgroup analyses found significantly lower risk of HF admissions with SGLT2i in those with a history of hospitalization for HF (0.58, 0.37-0.91; p-for-interaction=0.002) and current users of renin-angiotensin-system inhibitors without a neprilysin inhibitor (0.55, 0.33-0.92; 0.005).

Conclusions: With future studies using more contemporary data warranted, these preliminary findings in the meantime support current recommendations, thereby suggesting that SGLT2i may offer similar benefits for HF management when compared with ARNi, which may help healthcare providers with their clinical decision making.