Intensified background therapy enhances mortality benefit of SGLT2 inhibitors in heart failure: a retrospective cohort study

SGLT2 inhibitors (SGLT2is) improve outcomes in patients with heart failure (HF), but their effects may depend on background medical therapy. The Heart Failure Collaboratory score, which incorporates medication type and dose, may modify the benefit of SGLT2is. To evaluate the association between the scoring system and the mortality benefit of SGLT2 inhibitors in patients with heart failure. This retrospective multicenter cohort study used real-world data from the Chinese Cardiovascular Association Database–HF Center (HFC) Registry. 52 hospitals were selected with 26 HFCs and 26 NHFCs. Patients with a diagnosis of HF and one-year follow-up from July 1, 2022, to March 31, 2023, were included. The primary outcome was one-year all-cause mortality. Cox regression and multivariable fractional polynomial interaction (MFPI) models were used to assess the effect of SGLT2is on mortality risk across Heart Failure Collaboratory scores. A total of 4,077 patients (median age 70.0 years; 60.1% male) were included. SGLT2is was associated with reduced mortality risk in the overall population (adjusted hazard ratio (aHR) 0.71, 95% CI 0.60–0.85). A significant interaction was observed with the score (P interaction = 0.009), with SGLT2is therapy associated with a greater reduction in mortality risk among patients scoring ≥ 5 (aHR 0.60, 95% CI 0.46–0.78), whereas no significant association was observed in those scoring < 5 (aHR 0.98, 95% CI 0.76–1.26). MFPI analysis further demonstrated greater mortality risk reduction in SGLT2is user than nonuser, as the score increased (P interaction = 0.003), and also in patients with LVEF > 40% (P interaction = 0.021). The mortality benefit was more pronounced when other triple therapy agents were adequately applied. ChiCTR1800017226