Oral alfacalcidol did not reduce the risk for a composite outcome of cardiovascular (CV) events in patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, according to study results published in JAMA.
Tetsuo Shoji and his team of J-DAVID investigators set out to determine whether vitamin D receptor activators were helpful in reducing CV events and mortality in patients not suffering from secondary hyperparathyroidism undergoing hemodialysis.
Patients with chronic kidney disease are known to be at higher risk for CV events as a result of impaired vitamin D activation. Observational studies have shown that patients undergoing hemodialysis treatment who used vitamin D sterols were at lower risk for mortality regardless of parathyroid hormone levels.
Investigators conducted a randomized, open-label, blinded end point, multicenter study, drawing data from 1289 patients across 207 Japanese dialysis centers. Of the patients included in the study, 976 received maintenance hemodialysis with serum intact parathyroid hormone levels of ≤180 pg/mL. Of the total number of participants, 97.9% completed the trial.
The treatment consisted of 0.5 μg micrograms of oral alfacalcidor per day and was administered to 495 patients; the group of 481 control patients received no treatment. Participants were enrolled in the trial between August of 2008 and January of 2011, with a final follow-up date in April 2015. The result of the trial was a “composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalization for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death.”
The primary composite outcome of CV events occurred in 103 of 488 patients receiving the intervention treatment (21.1%) and 85 of 476 control patients (17.9%) at a confidence level of P =.13. There was no significant difference found in an analysis of the secondary outcome, all-cause mortality, between the intervention and control groups (P =.46).
Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events classified as CV, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. The 476 participants in the control group experienced the similar adverse events at rates of 40.1%, 13.2%, and 4.4%, respectively.
Given the apparent lack of difference in outcomes between the intervention group and the control group, the investigator’s findings do not support the use of vitamin D receptor activators for patients such as the individuals chosen for this study.
The J-DAVID Investigators, Shoji T, Inaba M, et al. Effect of oral alfacalcidol on clinical outcomes in patients without secondary hyperparathyroidism receiving maintenance hemodialysis: the J-DAVID randomized clinical trial. JAMA. 2018;320(22):2325.