A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study

Am J Kidney Dis. 2008 Jun;51(6):952-65. doi: 10.1053/j.ajkd.2008.02.298. Epub 2008 Apr 18.


Background: Previous clinical trials showed that progression of coronary artery calcification (CAC) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders. Because sevelamer decreases low-density lipoprotein cholesterol (LDL-C) levels, we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients.

Study design: Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8.

Setting & participants: 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL, LDL-C levels greater than 80 mg/dL, and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography.

Interventions: 103 patients were randomly assigned to calcium acetate, and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups.

Outcomes & measurements: The primary end point was change in CAC score assessed by means of electron-beam computed tomography.

Results: After 12 months, mean serum LDL-C levels decreased to 68.8 +/- 22.0 mg/dL in the calcium-acetate group and 62.4 +/- 23.0 mg/dL in the sevelamer group (P = 0.3). Geometric mean increases in CAC scores were 35% in the calcium-acetate group and 39% in the sevelamer group, with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 (95% confidence interval, 0.851 to 1.161).

Limitations: Treatment assignment was not blinded. The 1.8 a priori margin is large, CAC is a surrogate outcome, duration of treatment was short, and dropout rate was high.

Conclusions: With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.

Trial registration: ClinicalTrials.gov NCT00211939.

Publication types

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

MeSH terms

  • Acetates / therapeutic use*
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Calcinosis / prevention & control*
  • Calcium Compounds / therapeutic use
  • Chelating Agents / therapeutic use*
  • Coronary Artery Disease / prevention & control*
  • Disease Progression
  • Female
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Polyamines / therapeutic use*
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Renal Dialysis*
  • Sevelamer
  • Time Factors


  • Acetates
  • Anticholesteremic Agents
  • Calcium Compounds
  • Chelating Agents
  • Heptanoic Acids
  • Polyamines
  • Pyrroles
  • Sevelamer
  • Atorvastatin
  • calcium acetate

Associated data

  • ClinicalTrials.gov/NCT00211939