Shoji T, et al. - Among 976 patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, researchers determined whether vitamin D receptor activators reduce cardiovascular events and mortality. They observed that oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. The use of vitamin D receptor activators for patients without secondary hyperparathyroidism receiving maintenance hemodialysis was not supported in this investigation.

Methods

• It was a randomized, open-label, blinded end point multicenter study.
• The study sample consisted of 1289 patients in 207 dialysis centers in Japan.
• Eligible participants were 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL.
• The first and last participants were registered on August 18, 2008, and January 26, 2011.
• The final follow-up date was April 4, 2015.
• Interventions included treatment with 0.5 μg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481).
• A composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up was the primary outcome.
• All-cause death was the secondary outcome.

Results

• Of the 976 patients randomized from 108 dialysis centers, 964 were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial.
• The primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, −1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P=.13) during follow-up (median, 4.0 years).
• No significant difference was found in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P=.46).
• Of the 488 participants in the intervention group, 199 (40.8%) experienced serious cardiovascular adverse events, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced serious adverse events related to malignancy.
• Of the 476 control group participants, 191 (40.1%) experienced serious cardiovascular adverse events, 63 (13.2%) experienced serious adverse events related to infection and 21 (4.4%) experienced adverse events related to malignancy.