Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial

Am J Kidney Dis. 2013 Oct;62(4):771-8. doi: 10.1053/j.ajkd.2013.03.023. Epub 2013 May 16.


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.

Keywords: Cardiovascular mortality; chronic kidney disease; coronary artery calcification; sevelamer.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Calcium Carbonate / therapeutic use*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Coronary Artery Disease
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polyamines / therapeutic use*
  • Renal Dialysis*
  • Sevelamer
  • Single-Blind Method
  • Survival Rate
  • Time Factors


  • Polyamines
  • Sevelamer
  • Calcium Carbonate