Effects of Cinacalcet on Atherosclerotic and Nonatherosclerotic Cardiovascular Events in Patients Receiving Hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial

Abstract

BackgroundPremature cardiovascular disease limits the duration and quality of life on long‐term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial.Methods and ResultsEVOLVE was a randomized, double‐blind, placebo‐controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.ConclusionsAccepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.Clinical Trials RegistrationUnique identifier: NCT00345839. URL: ClinicalTrials.gov.

Prognostic Value of Serial Changes in High-Sensitivity Cardiac Troponin I and T over 3 Months Using Reference Change Values in Hemodialysis Patients

“…Furthermore, in the HEMO (Hemodialysis) and 4D (Deutsche Diabetes Dialyse Studie) trials, 22% and 26% of deaths, respectively, were sudden (20,21 ). In the EVOLVE [EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events] trial, the largest randomized dialysis trial, which enrolled 3883 hyperparathyroid HD patients, 25% of deaths were adjudicated as sudden deaths (22 ). The recently initiated WED-HED (Wearable Cardioverter Defibrillator in Hemodialysis Patients; NCT02481206) study is a randomized controlled trial testing the efficacy of wearable defibrillators for the prevention of SCD in incident HD patients.…”

Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment

“…Although the EVOLVE trial has not shown that cinacalcet improves survival in ESRD patients, a post hoc analysis suggests that this drug that lowers PTH may also lower the risk of sudden cardiac death and/or cardiac failure [69]. …”

Coronary artery disease screening and prognosis in incident dialysis patients

“…3 Hirahata Clinic, Tokyo, Japan. 4 Department of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan.…”

“…Although the underlying mechanism of the cardio-renal axis in patients with chronic kidney disease (CKD) has been determined in considerable detail over the past decade [1], cardiovascular disease is still a leading cause of death in maintenance dialysis patients worldwide [2,3] and also in Japan [4]. The accelerated progression of atherosclerosis during the conservative phase of CKD, before starting dialysis therapy [5], is thought to be one of the causes of the high incidence of cardiovascular events in the dialysis phase [6,7].…”