Qunibi Wajeh, Moustafa Moustafa, Muenz Larry R, He David Y, Kessler Paul D, Diaz-Buxo Jose A, Budoff Mathew
Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center, San Antonio, TX 78229-3900, USA.
Am J Kidney Dis. 2008 Jun;51(6):952-65. doi: 10.1053/j.ajkd.2008.02.298. Epub 2008 Apr 18.
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.
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.
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.
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).
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.
With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.
既往临床试验表明，与接受钙基磷结合剂治疗的血液透析患者相比，接受司维拉姆治疗的患者冠状动脉钙化（CAC）进展可能较慢。由于司维拉姆可降低低密度脂蛋白胆固醇（LDL-C）水平，我们推测，在接受醋酸钙治疗的血液透析患者中，使用阿托伐他汀强化降低LDL-C水平将导致CAC进展率与接受司维拉姆治疗的患者相似。
随机、对照、开放标签的非劣效性试验，非劣效性界值上限为1.8。
26个透析中心的203例维持性血液透析患者，血清磷水平大于5.5mg/dL，LDL-C水平大于80mg/dL，通过电子束计算机断层扫描评估的基线CAC评分为30至7000单位。
103例患者随机分配至醋酸钙组，100例患者分配至司维拉姆组，治疗12个月以将磷水平控制在3.5至5.5mg/dL。两组均加用阿托伐他汀以使血清LDL-C水平低于70mg/dL。
主要终点为通过电子束计算机断层扫描评估的CAC评分变化。
12个月后，醋酸钙组平均血清LDL-C水平降至68.8±22.0mg/dL，司维拉姆组降至62.4±23.0mg/dL（P = 0.3）。醋酸钙组CAC评分的几何平均增幅为35%，司维拉姆组为39%，协变量调整后的醋酸钙-司维拉姆比值为0.994（95%置信区间，0.851至1.161）。
治疗分配未设盲。先验界值1.8较大，CAC为替代结局，治疗持续时间短，且失访率高。
强化降低LDL-C水平1年，接受醋酸钙或司维拉姆治疗的血液透析患者经历了相似的CAC进展。
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