Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview.
OBJECTIVE
The dramatically high rates of mortality and cardiovascular morbidity observed among dialysis patients highlights the importance of identifying and implementing strategies to lower cardiovascular risk in this population. Results from clinical trials undertaken thus far, including trials on lipid reduction, normalization of hematocrit, and increased dialysis dosage, have been unsuccessful. Available data indicate that abnormalities in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism alone or the therapeutic measures used to manage secondary hyperparathyroidism, are associated with an increased risk for death and cardiovascular events. However, no prospective trials have evaluated whether interventions that modify these laboratory parameters result in a reduction in adverse cardiovascular outcomes.


METHODS
Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events is a global, phase 3, double-blind, randomized, placebo-controlled trial evaluating the effects of cinacalcet on mortality and cardiovascular events in hemodialysis patients with secondary hyperparathyroidism. Approximately 3800 patients from 22 countries will be randomly assigned to cinacalcet or placebo. Flexible use of traditional therapies will be permitted. The primary end point is the composite of time to all-cause mortality or first nonfatal cardiovascular event (myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular disease, including lower extremity revascularization and nontraumatic amputation).


RESULTS
The study will be event driven (terminated at 1882 events) with an anticipated duration of approximately 4 yr.


CONCLUSIONS
Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events will determine whether management of secondary hyperparathyroidism with cinacalcet reduces the risk for mortality and cardiovascular events in hemodialysis patients.
Chertow
Glenn M
GM
Department of Medicine, University of California at San Francisco, San Francisco, California, USA.
Pupim
Lara B
LB
Block
Geoffrey A
GA
Correa-Rotter
Ricardo
R
Drueke
Tilman B
TB
Floege
Jürgen
J
Goodman
William G
WG
London
Gerard M
GM
Mahaffey
Kenneth W
KW
Moe
Sharon M
SM
Wheeler
David C
DC
Albizem
Moetaz
M
Olson
Kurt
K
Klassen
Preston
P
Parfrey
Patrick
P
D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control*; D000069449:Cinacalcet; D004311:Double-Blind Method; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications* / Q000188:drug therapy*; D009281:Naphthalenes / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D006435:Renal Dialysis
D009281:Naphthalenes; D000069449:Cinacalcet