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.
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.


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


METHODS
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Qunibi
Wajeh
W
Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center, San Antonio, TX 78229-3900, USA. qunibi@uthscsa.edu
Moustafa
Moustafa
M
Muenz
Larry R
LR
He
David Y
DY
Kessler
Paul D
PD
Diaz-Buxo
Jose A
JA
Budoff
Mathew
M
D000085:Acetates / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002114:Calcinosis / Q000517:prevention & control*; D017610:Calcium Compounds / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000627:therapeutic use*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D006435:Renal Dialysis; D000069603:Sevelamer; D013997:Time Factors
D000085:Acetates; D000924:Anticholesteremic Agents; D017610:Calcium Compounds; D002614:Chelating Agents; D006538:Heptanoic Acids; D011073:Polyamines; D011758:Pyrroles; D000069603:Sevelamer; D000069059:Atorvastatin; C120662:calcium acetate