Cinacalcet Versus Placebo for Secondary Hyperparathyroidism in Chronic Kidney Disease Patients: a Meta-analysis of Randomized Controlled Trials and Trial Sequential Analysis

To assess the efficacy and safety of cinacalcet on secondary hyperparathyroidism in patients with chronic kidney disease, Pubmed, Embase, and the Cochrane Central Register of Controlled Trials were searched until March 2016. Trial sequential analysis (TSA) was conducted to control the risks of type I and II errors and calculate required information size (RIS). A total of 25 articles with 8481 participants were included. Compared with controls, cinacalcet administration did not reduce all-cause mortality (RR = 0.97, 95% CI = 0.89-1.05, P = 0.41, TSA-adjusted 95% CI = 0.86-1.08, RIS = 5260, n = 8386) or cardiovascular mortality (RR = 0.95, 95% CI = 0.83-1.07, P = 0.39, TSA-adjusted 95% CI = 0.70-1.26, RIS = 3780 n = 5418), but it reduced the incidence of parathyroidectomy (RR = 0.48, 95% CI = 0.40-0.50, P < 0.001, TSA-adjusted 95% CI = 0.39-0.60, RIS = 5787 n = 5488). Cinacalcet increased the risk of hypocalcemia (RR = 8.48, 95% CI = 6.37-11.29, P < 0.001, TSA-adjusted 95% CI = 5.25-13.70, RIS = 6522, n = 7785), nausea (RR = 2.12, 95% CI = 1.62-2.77, P < 0.001, TSA-adjusted 95% CI = 1.45-3.04, RIS = 4684, n = 7512), vomiting (RR = 2.00, 95% CI = 1.79-2.24, P < 0.001, TSA-adjusted 95% CI = 1.77-2.26, RIS = 1374, n = 7331) and diarrhea (RR = 1.17, 95% CI = 1.05-1.32, P = 0.006, TSA-adjusted 95% CI = 1.02-1.36, RIS = 8388, n = 6116). Cinacalcet did not significantly reduce the incidence of fractures (RR = 0.58, 95% CI = 0.21-1.59, P = 0.29, TSA-adjusted 95% CI = 0.01-35.11, RIS = 76376, n = 4053). Cinacalcet reduced the incidence of parathyroidectomy, however, it did not reduce all-cause and cardiovascular mortality, and increased the risk of adverse events including hypocalcemia and gastrointestinal disorders.