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Meta-Analysis
. 2018 Feb 15;8(1):3111.
doi: 10.1038/s41598-018-21397-8.

Cinacalcet versus Placebo for secondary hyperparathyroidism in chronic kidney disease patients: a meta-analysis of randomized controlled trials and trial sequential analysis

Guoqi Wang  1 , Hongyan Liu  2 , Chengzhi Wang  2 , Xiaojian Ji  3 , Weijun Gu  4 , Yiming Mu  5
Affiliations
Meta-Analysis

Cinacalcet versus Placebo for secondary hyperparathyroidism in chronic kidney disease patients: a meta-analysis of randomized controlled trials and trial sequential analysis

Guoqi Wang et al. Sci Rep. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow diagram for study selection.
Figure 2
Figure 2
Forest plot (A) and trial sequential analysis (B) on all-cause mortality in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 3
Figure 3
Forest plot (A) and trial sequential analysis (B) on cardiovascular mortality in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 4
Figure 4
Forest plot (A) and trial sequential analysis (B) on parathyroidectomy in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 5
Figure 5
Forest plot (A) and trial sequential analysis (B) on fractures in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 6
Figure 6
Forest plot (A) and trial sequential analysis (B) on all adverse events in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 7
Figure 7
Forest plot (A) and trial sequential analysis (B) on hypocalcaemia in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 8
Figure 8
Forest plot (A) and trial sequential analysis (B) on hypercalcaemia in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 9
Figure 9
Forest plot (A) and trial sequential analysis (B) on nausea in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 10
Figure 10
Forest plot (A) and trial sequential analysis (B) on vomiting in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 11
Figure 11
Forest plot (A) and trial sequential analysis (B) on diarrhoea in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 12
Figure 12
Forest plot (A) and trial sequential analysis (B) on muscle cramp or spasms in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
Figure 13
Figure 13
Forest plot (A) and trial sequential analysis (B) on hypotension in cinacalcet group versus control group. RRR: relative risk reduction, Pc: event proportion in control group.
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