The effect of icodextrin on peritoneal dialysis patients with congestive heart failure: a time-varying exposure design and target trial emulation approach

Introduction Icodextrin is an alternative peritoneal dialysis (PD) solution with favorable fluid management and metabolic properties. Given the limited evidence regarding the use of icodextrin in patients with pre-existing congestive heart failure (CHF), this study aimed to examine the association between icodextrin use and clinical outcomes in PD patients. Methods We conducted a retrospective cohort study using the Chang Gung Research Database (CGRD), including 1 800 eligible PD patients with CHF from 2005 to 2022 in Taiwan, followed through June 2023. Icodextrin users (≥50% of PD duration) were compared with non-users. Primary outcomes included all-cause mortality, cardiovascular mortality, sudden death, and major adverse cardiovascular events (MACE). Multivariable Cox proportional hazards models incorporating time-varying exposure to icodextrin were applied. To evaluate the robustness of our primary analysis, we conducted a target trial emulation framework and an alternative time-dependent data structure as sensitivity analyses. Results Icodextrin use was associated with lower risks of all-cause mortality (adjusted hazard ratio [HR]: 0.16, 95% confidence interval [CI]: 0.13–0.20), cardiovascular mortality (HR: 0.20, 95% CI: 0.13–0.30), sudden death (HR: 0.15, 95% CI: 0.11–0.19), and MACE (HR: 0.68, 95% CI: 0.58–0.80). Icodextrin users also showed associations with reduced risks of encapsulating peritoneal sclerosis and transition to hemodialysis but lower transplantation rates. Conclusions In PD patients with CHF, icodextrin use was independently associated with better survival and cardiovascular outcomes. These findings support its preferential use in high-risk PD populations and warrant further prospective investigation.