title: The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial.
abstract: Patients with end-stage renal disease often have derangements in calcium and phosphorus homeostasis and resultant secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and hypertension. We conducted a secondary analysis of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving hemodialysis with sHPT were randomly assigned to receive cinacalcet or placebo. We sought to examine whether the effect of cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal myocardial infarction, heart failure, hospitalization for unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4-20%) of the primary composite end point. The effect of cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: T I
authors.initials: TI
authors.lastname: Chang
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Abdalla
authors.affiliation: Hôpital Manhes, Paris, France.
authors.forename: G M
authors.initials: GM
authors.lastname: London
authors.affiliation: Denver Nephrology, Denver, CO, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Block
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Correa-Rotter
authors.affiliation: Picardie University School of Medicine and Pharmacy, Amiens, France.
authors.forename: T B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Floege
authors.affiliation: University of Minnesota, Minneapolis, MN, USA.|Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Herzog
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Indiana University School of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Health Sciences Center, St. John's, Newfoundland, Canada.
authors.forename: P S
authors.initials: PS
authors.lastname: Parfrey
authors.affiliation: University College London, London, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Dehmel
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Chertow
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D057966:Calcimimetic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D000069449:Cinacalcet / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059289:Vascular Stiffness
chemical_list: D057966:Calcimimetic Agents; D000069449:Cinacalcet