Issue: 2013 > September > review

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

M.G. Vervloet, P.W.G. du Buf-Vereijken, B-J. Potter van Loon, N. Manamley, L.J.M. Reichert, P.J.H. Smak Gregoor


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present previously unpublished mineral metabolism data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.