A randomised controlled trial to examine the effects of cinacalcet on bone, cardiovascular parameters and mortality in haemodialysis patients with secondary hyperparathyroidism

Abstract

Background Secondary hyperparathyroidism may lead to increased cardiovascular risk. The use of cinacalcet may improve bone and cardiovascular health with improved parathormone (PTH) and phosphate control. Methods This is an open-label prospective randomised controlled trial to compare progression of cardiovascular and chronic kidney disease mineral and bone disorder (CKD-MBD) parameters. Patients were randomised to receive cinacalcet alongside standard therapy or standard therapy alone. 36 haemodialysis patients who had >90 days on dialysis, iPTH >300pg/mL, calcium >2.1mmol/L and age 18-75 years were included. Following randomization, all 36 patients underwent an intensive 12-week period of bone disease management aiming for iPTH 150-300pg/mL. The primary outcome was change in vascular calcification using CT agatston score. Secondary outcomes included pulse wave velocity (PWV), left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), augmentation index (Aix) and bone measurements. The above measurements were obtained at baseline and 12 months. The difference in mortality between the groups was compared during long-term follow-up. Results There was no evidence of a group difference in the progression of calcification (median change (IQR) cinacalcet: 488 (0 to1539); standard therapy: 563 (50 to 1214)). In a post hoc analysis combining groups there was a mean (SD) phosphate reduction of 0.3mmol/L (0.7) and median (IQR) iPTH reduction of 380pg/mL (-754, 120). Regression of LVMI and CIMT was seen (P=0.03 and P=0.001) and was significantly associated with change of phosphate on multi-factorial analyses. Over a median follow-up of 32 months, there was no significant difference in the mortality between the two groups.Conclusions No significant benefit in bone and cardiovascular markers was seen with the addition of cinacalcet to standard therapy over one year. Tight control of hyperphosphataemia and secondary hyperparathyroidism may lead to a reduction in LVMI and CIMT but this needs further investigation. Although the sample size was small, meticulous trial supervision resulted in very few protocol deviations with therapy.