title: Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism.
abstract: BACKGROUND
  Secondary hyperparathyroidism (HPT) and abnormal mineral metabolism are thought to play an important role in bone and cardiovascular disease in patients with chronic kidney disease. Cinacalcet, a calcimimetic that modulates the calcium-sensing receptor, reduces parathyroid hormone (PTH) secretion and lowers serum calcium and phosphorus concentrations in patients with end-stage renal disease (ESRD) and secondary HPT.
  
  
  METHODS
  We undertook a combined analysis of safety data (parathyroidectomy, fracture, hospitalizations, and mortality) from 4 similarly designed randomized, double-blind, placebo-controlled clinical trials enrolling 1184 subjects (697 cinacalcet, 487 control) with ESRD and uncontrolled secondary HPT (intact PTH > or =300 pg/mL). Cinacalcet or placebo was administered to subjects receiving standard care for hyperphosphatemia and secondary HPT (phosphate binders and vitamin D). Relative risks (RR) and 95% CI were calculated using proportional hazards regression with follow-up times from 6 to 12 months. Health-related quality-of-life (HRQOL) data were obtained from the Medical Outcomes Study Short Form-36 (SF-36), and the Cognitive Functioning scale from the Kidney Disease Quality of Life instrument (KDQOL-CF).
  
  
  RESULTS
  Randomization to cinacalcet resulted in significant reductions in the risk of parathyroidectomy (RR 0.07, 95% CI 0.01-0.55), fracture (RR 0.46, 95% CI 0.22-0.95), and cardiovascular hospitalization (RR 0.61, 95% CI 0.43-0.86) compared with placebo. Changes in HRQOL favored cinacalcet, with significant changes observed for the SF-36 Physical Component Summary score and the specific domains of Bodily Pain and General Health Perception.
  
  
  CONCLUSIONS
  Combining results from 4 clinical trials, randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization, along with improvements in self-reported physical function and diminished pain. These data suggest that, in addition to its effects on PTH and mineral metabolism, cinacalcet had favorable effects on important clinical outcomes.
authors.affiliation: University College London, The Middlesex Hospital, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Cunningham
authors.forename: Mark
authors.initials: M
authors.lastname: Danese
authors.forename: Kurt
authors.initials: K
authors.lastname: Olson
authors.forename: Preston
authors.initials: P
authors.lastname: Klassen
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality*; D000069449:Cinacalcet; D005260:Female; D050723:Fractures, Bone / Q000401:mortality*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000401:mortality*; D007676:Kidney Failure, Chronic / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D009281:Naphthalenes; D000069449:Cinacalcet