Clinical Outcomes in Secondary Hyperparathyroidism and the Potential Role of Calcimimetics

Cinacalcet, a type II calcimimetic agent that interacts with the calcium-sensing receptor on the parathyroid gland and increases its sensitivity to calcium, has proved an effective therapy for the treatment of the biochemical derangements that comprise uraemic secondary hyperparathyroidism. These patients experience high cardiovascular attrition with evidence that this is associated with vascular calcification, arterial stiffening and increased pulse wave velocity, and with some of the disturbances of bone and mineral metabolism in uraemia. Thus, it is possible that improved biochemical control in calcimimetic-treated patients might lead to better clinical outcomes. This hypothesis was investigated by retrospective analyses of randomized placebo-controlled phase 3 studies. The addition of cinacalcet to standard therapy with active vitamin D and phosphate binders was found to result in a 93% reduction in the rate of parathyroidectomy, a 54% reduction in fracture rate and 39% reduction in the rate of cardiovascular hospitalization, as well as improvements in some measures of quality of life. These encouraging results point to the need for a more robust assessment of the impact of cinacalcet on cardiovascular and skeletal outcomes.