S2I2N0–3 score predicts short‐ and long‐term mortality and morbidity in HFrEF: a post‐hoc analysis of the GUIDE‐IT trial

Abstract

Abstract Aims This study investigated the S2I2N0–3 score, a simple tool comprising stroke history, insulin‐treated diabetes, and N‐terminal pro‐brain natriuretic peptide, for forecasting mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Analysing 890 GUIDE‐IT HFrEF trial participants, we stratified them by baseline S2I2N0–3 risk score into three risk groups. We examined the score's association with five adverse outcomes over short (90 days) and extended periods (median follow‐up of 15 months) using Cox and competing risk models. Our analysis revealed significant positive associations between the S2I2N0–3 strata and adverse outcomes. When analysed as a continuous variable, each point increment of the S2I2N0–3 score was associated with a higher risk of short‐ and long‐term cardiovascular death [short term: hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.03–1.98; long term: HR 1.18, 95% CI 1.02–1.38], all‐cause death (HR 1.52, 95% CI 1.12–2.07; HR 1.18, 95% CI 1.03–1.36), HF hospitalization (HR 1.39, 95% CI 1.20–1.62; HR 1.18, 95% CI 1.06–1.31), any hospitalization (HR 1.19, 95% CI 1.06–1.34; HR 1.09, 95% CI 1.00–1.19), and the composite outcome of cardiovascular death and HF hospitalization (HR 1.39, 95% CI 1.21–1.60; HR 1.17, 95% CI 1.06–1.30). The S2I2N0–3 demonstrated reliable prognostic value, with C‐indices ranging from 0.619 to 0.753 across outcomes and time points. When compared with the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score using Z‐statistics, net reclassification index, and integrated discrimination improvement, the S2I2N0–3 showed comparable predictive power for all outcomes during both short‐ and long‐term follow‐ups. Conclusions The S2I2N0–3 risk score had modest predictive values for both short‐ and long‐term clinical outcomes in HFrEF patients, offering equivalent performance to the established MAGGIC score.

Keywords

• Heart failure
• S2I2N0–3
• Risk score
• Risk stratification
• Predictive value