Cinacalcet for secondary hyperparathyroidism: from improved mineral levels to improved mortality?

Abstract

Secondary hyperparathyroidism is an almost inevitable complication of advanced kidney failure. The introduction of the calcimimetic cinacalcet for the treatment of secondary hyperparathyroidism in patients on dialysis was based on its ability to reduce elevated levels of parathyroid hormone (PTH). Subsequent clinical studies confirmed the beneficial effects of cinacalcet on biochemical parameters reflecting mineral disturbances and bone disease. In this review we summarise the impact of cinacalcet on biochemical, intermediate and clinical outcomes. We also present previously unpublished mineral metabolism data from 144 Dutch dialysis patients treated with cinacalcet who participated in the pan-European ECHO observational study. Although secondary hyperparathyroidism tended to be more severe in our Dutch cohort, compared with the entire ECHO cohort, cinacalcet was nevertheless effective in reducing PTH in these patients. Two recent clinical studies evaluated, respectively, the efficacy of cinacalcet in improving the intermediate endpoint of cardiovascular calcifications (ADVANCE trial), and its impact on clinical outcomes, including all-cause mortality and cardiovascular events (EVOLVE trial). The ADVANCE trial provided evidence that cinacalcet may indeed improve calcification in both large arteries and cardiac valves. The EVOLVE trial, however, did not meet its clinical primary endpoint (time to all-cause mortality, myocardial infarction, hospitalisation for unstable angina, heart failure or a peripheral vascular event), although secondary and sensitivity analysis suggested a beneficial effect. The clinical implications of these important studies are also addressed in this review.