| [ Summary ] |
Cinacalcet acts on calcium-sensing receptors (CaR) expressed on the chief cells of the parathyroid gland to inhibit parathyroid hormone (PTH) secretion. Unlike active vitamin D, cinacalcet inhibits serum PTH secretion without elevating serum calcium and phosphorus levels. Several studies have demonstrated the inhibitory effect of calcimimetics on the progression of vascular calcification in animals with chronic kidney disease (CKD) due to the expression of CaR in vascular tissue. For example, the EVOLVE trial evaluated the effects of cinacalcet on the progression of vascular calcification and hard cardiovascular outcomes in patients with CKD stage 5D. This trial used an intent-to-treat analysis and missed its primary endpoint. However, in order to define the frequency of fatal and nonfatal cardiovascular events attributed to atherosclerotic and nonatherosclerotic mechanisms, the risk factors for these events, and the effects of cinacalcet, a post hoc analysis was recently performed using adjudicated data collected during the EVOLVE trial. In this trial, randomization to receive cinacalcet showed a reduction in the rates of sudden death and heart failure. Patients randomized to treatment with cinacalcet also experienced fewer nonatherosclerotic cardiovascular events, while the effect of cinacalcet on atherosclerotic events was not statistically significant. Although cinacalcet is the only approved oral calcimimetic and the first agent to lower serum intact parathyroid hormone (iPTH) level without increasing serum calcium and phosphorus levels, its clinical use has been limited because of a high frequency of nausea and vomiting. Therefore, novel CaR agonists have been developed. |