Meta-analysis of biochemical and patient-level effects of calcimimetic therapy

Background: Many randomized trials have now evaluated the effects of calcimimetics in patients with chronic kidney disease and secondary hyperparathyroidism (SHPT) on standard therapy with vitamin D and/or phosphate binders. We conducted a meta-analysis to evaluate outcomes of therapy with these novel agents. Methods: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and conference proceedings were searched for randomized controlled trials evaluating any calcimimetic against placebo or another agent in predialysis or dialysis patients with chronic kidney disease. Data were extracted for all relevant patient-centered and surrogate outcomes. Analysis was by means of a random-effects model, and results are expressed as relative risk or weighted mean difference (WMD) with 95% confidence intervals (CIs). Results Eight trials (1,429 patients) were identified that compared a calcimimetic agent plus standard therapy with placebo plus standard therapy. End-of-treatment values for parathyroid hormone (4 trials; 1,278 patients; WMD, -290.49 pg/mL; 95% Cl, -359.91 to -221.07), serum calcium (3 trials; 1,201 patients; WMD, -0.85 mg/dL; 95% Cl, -1.14 to -0.56), serum phosphorus (3 trials; 1,195 patients; WMD, -0.29 mg/dL; 95% Cl, -0.50 to -0.08), and calcium x phosphorus product (3 trials; 1,194 patients; WMD, -7.90 mg(2)/dL(2); 95% Cl, -10.25 to -5.54) were significantly lower with calcimimetic therapy compared with placebo. No significant effects on patient-based end points were shown. Conclusion: Calcimimetic treatment of patients with SHPT leads to significant improvements in biochemical parameters that observational studies have associated with increased mortality, cardiovascular risk, and osteitis fibrosa, but patient-based benefits have not yet been shown. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until additional randomized trials become available.