Real-world impact of intermittent levosimendan on survival, hospitalizations, and healthcare costs in advanced heart failure

Abstract Introduction Advanced heart failure (HF) is a major healthcare challenge leading to high morbidity, frequent hospitalizations, and significant economic burden. Intermittent levosimendan (iLev) has been associated with a reduction in HF admissions, however its impact on survival outcomes and economic burden is still not well established in a real-world setting. Purpose To assess the prognostic impact of iLev in advanced HF patients by evaluating its effects on survival, hospitalizations, emergency room (ER) visits, and overall healthcare costs. Methods This single-center, prospective, one-arm study included consecutive advanced HF patients receiving iLev in a tertiary hospital. The number of HF-related admissions and ER visits after iLev was compared to the same period before treatment. Survival analysis was performed comparing baseline predicted life expectancy (PLE) using the Seattle Heart Failure Model (SHFM) with observed survival. For patients who neither surpassed their PLE nor died at follow-up, a recalculated PLE was used to estimate survival benefit. Cost analysis was based on standardized Ministry of Health rates for hospitalizations, ER visits, and outpatient iLev administrations. Statistical analysis included the Wilcoxon Signed-Rank Test, Kaplan-Meier survival analysis, and Cox regression. Results A total of 34 advanced HF patients (79.4% male; median age 68 years and baseline LV ejection fraction 24%; 82,4% in NYHA class III) were included, with a median follow-up of 1.3 years (IQR 0.7–2.7). Survival analysis showed that 35.3% exceeded their baseline PLE, 32.4% died before reaching it, and 32.3% remained alive but had not reached it at follow-up. The median baseline PLE was 30.5 months (IQR 21–44), while observed survival or recalculated PLE was 39.5 months (IQR 11–54.25). Survival probability significantly improved compared to baseline PLE (HR 0.409; 95% CI 0.224–0.747; p=0.004 – Figure 1). The median number of HF admissions per patient decreased from 4 (IQR 2–5) to 2 (IQR 1–3) (p0.001), while ER visits dropped from 5 (IQR 3–14) to 2 (IQR 1–5) (p0.001). A total of 283 iLev infusions were administered (142 inpatient 24-hour and 141 outpatient 6-hour). Mean cost per patient before iLev was €17,298.00 (IQR €8,957–23,696), decreasing to €10,682.50 (IQR €6,268–18,540) post-treatment initiation (p=0.010). The average savings per patient was €4,112.76, primarily due to fewer hospitalizations. Conclusion Intermittent levosimendan was associated with improved survival, fewer hospitalizations and ER visits, and significant cost savings in advanced HF patients. These findings support its role as an effective adjunctive therapy even in a real-world setting.