Sevelamer Versus Calcium Carbonate in Incident Hemodialysis Patients: Results of an Open Label 24-Month Randomized Clinical Trial.

Background: Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis remains to be elucidated. Study Design: Open-label randomized controlled trial with parallel groups. Settings & Participants: 466 incident hemodialysis patients recruited from 18 centers in Italy. Intervention: Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate) for 24 months. Outcomes: All individuals were followed up until completion of 36 months of follow-up or censoring. CV death due to cardiac arrhythmias was regarded as the primary end point. Measurements: Blind event adjudication. Results: At baseline, patients allocated to sevelamer had higher serum phosphorus (mean, 5.6 ± 1.7 [SD] vs 4.8 ± 1.4 mg/dL) and C-reactive protein levels (mean, 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL) and lower coronary artery calcification scores (median, 19 [IQR, 0-30] vs 30 [IQR, 7-180]). At study completion, serum phosphate levels were lower in the sevelamer arm (median dosages, 4,800 and 2,000 mg/d for sevelamer and calcium carbonate, respectively). After a mean follow-up of 28 ± 10 months, 128 deaths were recorded (29 and 88 due to cardiac arrhythmias and all-cause CV death). Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate (HR, 0.06; 95% CI, 0.01-0.25; P < 0.001). Similar results were noted for all-cause CV mortality and all-cause mortality, but not for non-CV mortality. Adjustments for potential confounders did not affect results. Limitations: Open-label design, higher baseline coronary artery calcification burden in calcium carbonate-treated patients, different mineral metabolism control in sevelamer-treated patients, overall lower than expected mortality. Conclusions: These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients. However, the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load