SEVELAMER ATTENUATES CV MORTALITY IN INCIDENT HEMODIALYSIS PATIENTS: OPEN LABEL, RANDOMIZED CLINICAL TRIAL OF EFFICACY AND SAFETY (INDEPENDENT STUDY)

INTRODUCTION AND AIMS: Whether the choice of sevelamer (SV) compared to calcium-based phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis still remains to be elucidated. We herein report on an open label, blocked-randomized, multi-centered controlled trial with masked allocation, aimed at evaluating the impact of SV on CV survival in incident dialysis patients. METHODS: A total of 466 individuals were randomized to receive either SV or calcium salts (CS) as phosphate binders (figure 1). All individuals were followed until study completion or CV death occurrence. All-cause mortality and non-CV mortality were investigated as secondary endpoints. The Independent study was registered on ClinicalTrials.Gov as the Reduce Cardiovascular Calcifications to Reduce QT Interval in Dialysis (INDEPENDENT) Study, number NCT00710788 RESULTS: Overall, we recruited middle-age (mean age 65+14 years) men (49%) and women (51%). Hypertension (79%), CV disease (36%) and diabetes (29%) were the most common comorbid conditions. At baseline, patients allocated to SV had higher serum phosphorus levels and lower CAC scores (CACS) compared to patients allocated to CS. After a mean follow-up of 28 (10) months, SV treated patients experienced a 10-fold lower CV mortality compared to patients treated with CS as binders (p<0.001) (figure 2). Similar results were noted for the allcause but not for the non-CV mortality. Adjustments for potential confounders did not affect these results (Table 1). Further analyses stratifying for CACS at baseline did not attenuate the survival benefit of SV that persisted in all CACS strata. CONCLUSIONS: This study shows that SV increases significantly CV survival in a population of incident hemodialysis patients. The large survival benefit demonstrated with the intervention evaluted in this RCT contrasts with the absense of benefit reported for other interventions in this patient population. Thus, this study demonstrates that a simple relatively inexpensive treatment decision may significantly improve patient survival in incident dialysis patients.