Real-World Evidence for Sevelamer vs Calcium-Containing Phosphate Binders in Long-Term Effectiveness and Safety Among Patients with Non-Dialysis CKD: The REVEAL Study

INTRODUCTION: Elevated serum phosphate is a major risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). Both calcium- and non-calcium-containing phosphate binders (CPBs and NCPBs) are effective at lowering serum phosphate in patients with non-dialysis-dependent CKD (ND-CKD). The critical knowledge gap is whether CPBs or NCPBs provide meaningful long-term benefits for patients with ND-CKD, including slowing progression to end-stage renal disease (ESRD) and reducing cardiovascular events. METHODS: administrative claims data from between 1 August 2000 and 30 November 2021. Adults with ND-CKD and hyperphosphataemia or serum phosphorus ≥ 1.78 mmol/L (≥ 5.5 mg/dL) who had received either sevelamer (a NCPB) or a CPB for ≥ 90 days underwent propensity score matching (PSM) to balance baseline characteristics. The primary endpoint was initiation of renal replacement therapy (RRT) over 3 years. Secondary composite endpoints were the incidence of major adverse cardiovascular events (MACE; myocardial infarction, stroke and all-cause death) and MACE plus (MACE, unstable angina pectoris and heart failure). RESULTS: Of 9047 patients who underwent PSM (sevelamer, n = 6644; CPBs, n = 2403), data from 4798 were analysed (2399 in each group). Over 3 years, RRT initiation had significantly lower incidence with sevelamer than CPBs (65.0% vs 70.3%; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.79-0.91, P < 0.0001). MACE (44.9% vs 50.7%; HR 0.91, 95% CI 0.84-0.99, P = 0.0249) and MACE plus (51.9% vs 59.1%; HR 0.88, 95% CI 0.81-0.95, P = 0.0009) also had significantly lower incidence with sevelamer than CPBs. RRT initiation had significantly lower incidence with sevelamer versus CPB in subgroup analyses by age, sex, race, disease stage and medical history. CONCLUSION: In this real-world long-term study, sevelamer was associated with beneficial outcomes over CPBs for hyperphosphataemia treatment in patients with ND-CKD. Further definitive studies are needed to confirm this finding.