Cinacalcet and Clinical Outcomes in Dialysis

Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal disease and is one of the most prominent causes of a markedly increased risk of death and cardiovascular disease in this patient population. Cinacalcet hydrochloride is a new option for the treatment of SHPT, and the efficacy and effectiveness to lower parathyroid hormone levels and to improve control of mineral metabolism, even in patients with severe disease, has been well established in many clinical trials and observational studies. Currently, the focus has moved to the impact of cinacalcet on hard clinical outcomes, and two randomized controlled trials, ADVANCE and EVOLVE, have been performed to assess the effects of cinacalcet on cardiovascular calcification and the risk of cardiovascular events and mortality, respectively. Although the primary analysis of both trials did not find significant effects of cinacalcet, the benefit of cinacalcet was suggested in the subanalyses in which the potential problems of the trials were taken into account. These positive results are consistent with experimental studies showing favorable effects of cinacalcet on bone metabolism and vascular calcification, providing plausibility to support the beneficial effects of cinacalcet. Definitive evidence is, however, still lacking, and further efforts should be made to establish the optimal role of cinacalcet in the treatment of SHPT.