Yokoyama Keitaro
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Japan.
Clin Calcium. 2015 May;25(5):729-36.
Cinacalcet acts on calcium receptors (CaR) expressed on chief cells of the parathyroid gland to inhibit the secretion of parathyroid hormone (PTH) . This drug inhibits PTH secretion without causing an elevation of serum calcium and phosphorus, unlike active vitamin D. Several experimental studies demonstrated an inhibitory effect of calcimimetics on the progression of vascular calcification in animals with chronic kidney disease (CKD), in keeping with the expression of the calcium-sensing receptor (CaSR) in vascular tissue. The EVOLVE, evaluated in patients with CKD 5D the effects of the cinacalcet on the progression of vascular calcification and hard cardiovascular outcomes, respectively. The EVOLVE trials missed their respective primary end point by intent-to-treat analysis. However, recently, in order to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, post hoc analysis using adjudicated data collected during the EVOLVE Trial were perfomed. In this trial, combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events, while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.
西那卡塞作用于甲状旁腺主细胞上表达的钙受体（CaR），以抑制甲状旁腺激素（PTH）的分泌。与活性维生素D不同，这种药物抑制PTH分泌而不会导致血清钙和磷升高。多项实验研究表明，拟钙剂对慢性肾脏病（CKD）动物的血管钙化进展具有抑制作用，这与血管组织中钙敏感受体（CaSR）的表达情况相符。EVOLVE研究分别评估了西那卡塞对CKD 5D患者血管钙化进展和严重心血管结局的影响。通过意向性分析，EVOLVE试验未达到各自的主要终点。然而，最近，为了确定归因于动脉粥样硬化和非动脉粥样硬化机制的致命和非致命心血管事件的发生率、这些事件的危险因素以及西那卡塞的作用，利用在EVOLVE试验期间收集的经裁定的数据进行了事后分析。在该试验中，将致命和非致命心血管事件合并后，随机分配至西那卡塞组可降低猝死和心力衰竭的发生率。随机分配至西那卡塞组的患者发生非动脉粥样硬化心血管事件的情况较少，而西那卡塞对动脉粥样硬化事件的影响未达到统计学显著性。
