ESC Congress 2026 Abstract · Oct 26, 2026

Association between sodium-glucose cotransporter 2 inhibitor therapy and outcome in 1,775 congenital heart disease patients – Application of an active comparator new user design

By Benesch Vidal ML, Strotmann S, Orwat S et al.

Background: Heart failure (HF) is highly prevalent in congenital heart disease (CHD), driving morbidity and mortality. Evidence supporting sodium–glucose cotransporter-2 inhibitors (SGLT2i) in CHD remains scarce, largely due to the absence of randomised trials in this specific patient group. Purpose: To evaluate the prognostic association of SGLT2i use in CHD using an active comparator new user design (ACNUD). Methods: Within a nationwide administrative database, CHD patients newly initiated on SGLT2i were identified and compared with active new users of mineralocorticoid receptor antagonists (MRAs). Propensity-score matching and multivariable time-dependent Cox regression were applied, adjusting for age, gender, CHD complexity, comorbidities, diabetes, prior emergency admissions, and concomitant HF therapy. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of all-cause mortality or cardiac-related emergency admission. Results: A total of 1,775 CHD patients received SGLT2i (median age 68 [IQR 57–79] years; 44% women) and were compared with 4,460 new MRA users (median age 67 [48-79] years; 50% female). SGLT2i recipients more frequently had diabetes (68% vs. 30%), obesity (56% vs. 36%), renal dysfunction (44% vs. 37%), and arterial hypertension, whereas heart failure and prior emergency admissions were more prevalent among MRA users (Table 1). Median follow-up was 445 [IQR 409–501] days and 1,565 [1,502–1,616] days in the SGLT2i and MRA group, respectively. In the SGLT2i cohort, 197 patients died and 697 experienced cardiac-related emergency admissions, compared with 1,200 deaths and 2,663 admissions among MRA users. After multivariable adjustment, SGLT2i therapy was associated with significantly lower all-cause mortality (HR 0.60; 95% CI 0.49–0.74; p<0.001) and reduced risk of the composite endpoint (HR 0.72; 95% CI 0.65–0.80; p<0.001) compared with new MRA users (Figure 1). Independent predictors of mortality included increasing age, heart failure, renal dysfunction (HR 1.50, p<0.001), prior diuretic therapy, and cardiac glycoside use. Female gender, arterial hypertension (HR 0.58; all p<0.001), prior ARB therapy, beta-blocker use, and implantable cardioverter-defibrillator implantation were associated with lower mortality risk. For the composite endpoint, age, stroke, heart failure, diabetes, renal dysfunction (HR 1.29; p<0.001), and prior diuretic therapy were independently associated with increased risk, whereas ARB therapy and ICD implantation were protective. Conclusions: In this nationwide CHD cohort analysed using an ACNUD, initiation of SGLT2i therapy was independently associated with improved survival and fewer cardiac-related emergency admissions compared with new MRA use. These findings demonstrate the feasibility of robust comparative effectiveness research in CHD and provide real-world evidence addressing the persistent lack of randomised trial data in this high-risk population.

doi.org/10.1093/eurheartj/ehag785.2490 Open access Interventions