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.

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.

Index Words: Cardiovascular disease, hyperphosphatemia, dialysis, vascular calcification, secondary hyperparathyroidism, electron-beam computed tomography (EBCT), low-density lipoprotein, statins, atorvastatin, cholesterol, dyslipidemia