n engl j med 368;19 nejm.org may 9, 2013 1842 The new england journal of medicine correspondence Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis To the Editor: The EVOLVE (Evaluation of Cina- calcet Hydrochloride Therapy to Lower Cardio- vascular Events) trial described by Chertow et al. (Dec. 27 issue) 1 regrettably is an addition to many negative studies involving patients with end-stage renal disease. These studies include the Hemodialysis (HEMO) Study, the 4D Study (Randomized Controlled Trial on the Efficacy and Safety of Atorvastatin in Patients with Type 2 Diabetes on Hemodialysis), AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Sur- vival and Cardiovascular Events), and SHARP (Study of Heart and Renal Protection). In the EVOLVE trial, cinacalcet reduced levels of parathyroid hormone effectively but did not lead to a statistically significant reduction in the risk of death or cardiovascular events. We think that this trial failed because of the insufficient definition of secondary hyperparathyroidism as an indication for cinacalcet (parathyroid hormone level >300 pg per milliliter). Levels of parathy- roid hormone were measured with second-gener- ation assays, which interfere with N-terminally truncated parathyroid hormone fragments. 2 A total of 30 to 50% of these patients may not have had histologic signs of secondary hyperpara- thyroidism, as suggested by their normal bone- specific alkaline phosphatase values. 3 Parathyroid hormone values greater than 600 pg per milli- liter are incidentally associated with adynamic bone disease in patients undergoing dialysis who are treated with high doses of active vitamin D analogues (12 to 24 μg per week), as were 70% of patients in this study. 4 Adynamic bone disease is due, in part, to vitamin D–induced skeletal parathyroid hormone receptor down-regulation and accumulation of N-terminally truncated para- thyroid hormone fragments. We wonder whether the results of this trial would have been different if all enrolled patients had had true secondary hyperparathyroidism (parathyroid hormone level >300 pg per milliliter and a bone alkaline phos- phatase level >20 ng per milliliter) or a parathy- roid hormone level measured by means of third- generation assays. Both factors are associated with a risk of death that is higher than the risk associated with parathyroid hormone levels mea- sured by means of second-generation assays. 5 Pablo Urena-Torres, M.D., Ph.D. Clinique du Landy Saint Ouen, France urena.pablo@wanadoo.fr Dominique Prié, M.D., Ph.D. Jean-Claude Souberbielle, M.D., Ph.D. Hôpital Necker Paris, France Dr. Urena-Torres reports receiving consulting fees from Am- gen, Abbott, Novartis, and Fresenius. No other potential con- flict of interest relevant to this letter was reported. this week’s letters 1842 Cinacalcet for Cardiovascular Disease in Patients Undergoing Dialysis 1845 Autophagy in Human Health and Disease 1846 Tragedy’s Legacy 1848 Pooled Platelet Concentrates or Apheresis Platelets? 1850 HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression 1852 Revision The New England Journal of Medicine Downloaded from nejm.org by PABLO URENA on May 11, 2013. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved.