Abstract Body (Do not enter title and authors here): Background: Heart failure is the leading cause of death in patients with congenital heart disease (CHD). We used longitudinal health insurance data and robust statistical methods to emulate randomized trials and examine the prognostic impact of Sodium-glucose cotransporter 2 inhibitors (SGLT-2I) and Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in CHD patients.


Methods: All CHD patients treated with SGLT-2/ARNIs in a nationwide health insurance dataset were included. The prognostic impact of SGLT-2/ARNIs was assessed using propensity score matching and multivariable time-dependent Cox analysis in comparison to an untreated control group and a cohort of patients commenced on mineralocorticoid antagonists (MRAs). Multivariable adjusting was performed for underlying disease complexity, co-morbidities, diabetes and heart failure medication. The primary outcome was all-cause mortality, the secondary outcome emergency hospital admission free survival.


Results: In total 1,049 CHD patients were treated with SGLT-2I and/or ARNIs (59.2% male, CHD complexity: 71 % mild, 20% moderate, and 9% complex CHD). Of these, 838 patients received ARNIs and 639 SGLT-2 inhibitors (57% empagliflozin, 39% dapagliflozin). In comparison with a propensity score matched untreated control group (n=333), patients with SGLT-2 therapy had a significantly lower all-cause mortality (Hazard-ratio [HR] 0.5; 95% CI 0.28-0.91; p=0.02). Compared to patients commenced on MRAs, patients treated with SGLT-2I or ARNIs had a significantly lower mortality rate (HR 0.73; 95% CI 0.59-0.91; p=0.005) and a superior emergency admission free survival rate (HR 0.69; 95% CI 0.60-0.80; p<0.001) after multivariable adjustment for demographics, pre-existing conditions, CHD complexity, diabetes and concomitant medication. This effect was most pronounced for SGLT-2 inhibitors (HR for mortality 0.47, p<0.001; emergency admission free survival 0.63, p<0.001 vs. MRA) and consistent across complexity groups, being most evident in CHD patients of moderate complexity: HR for mortality 0.5, p=0.015; emergency admission free survival 0. 47, p<0.001 vs. MRA)

Conclusion: SGLT-2 inhibitors/ARNIs are associated with significantly reduced all-cause mortality and risk of death or emergency admission in CHD regardless of disease complexity, co-morbidities, diabetes, and co-existing heart failure medication and should be considered for routine treatment of CHD heart failure patients.