Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients.

BACKGROUND The relative effectiveness and safety of sevelamer for treatment of hyperphosphataemia in dialysis patients is uncertain, as compared with calcium-based phosphate binders. METHODS We conducted a comprehensive search to identify all randomized cross-over or parallel group studies comparing sevelamer to any other therapy or placebo in adult dialysis patients. Study quality was assessed using the Chalmers Index. Data was extracted and checked using a standardized form and combined using a random effects model. RESULTS We identified 14 primary publications of randomized trials (3193 participants) that were eligible for efficacy analysis. In analyses pooling, the 10 studies reporting on serum phosphate and calcium (2501 participants), serum phosphate was significantly lower with calcium-based phosphate binders by 0.12 mmol/l [95% confidence interval (CI) 0.05-0.19], compared with sevelamer. On-treatment calcium-phosphate product was not significantly lower in patients receiving calcium-based phosphate binders (0.12 mmol(2)/l(2), -0.05 to 0.29), compared with sevelamer. Overall mean difference in serum calcium was significantly lower with sevelamer therapy by 0.10 mmol/l (-0.12 to -0.07) and pooled on-treatment decrease in serum bicarbonate was significantly greater with sevelamer therapy by 2.8 mmol/l (2.2 to -3.5). In the five trials which reported all-cause mortality (2429 participants), the overall risk difference for all cause mortality in these five trials was similar between therapies (-2%, 95% CI -6-2). In the three trials which reported serious adverse events (2185 participants), there was a trend towards a lower risk in patients receiving calcium-based phosphate binders (13% lower, 95% CI -2-29). CONCLUSIONS Compared with calcium-based phosphate binders, use of sevelamer in dialysis patients is associated with similar to slightly higher phosphate levels, similar calcium phosphate product, and slightly lower serum calcium levels. There was no evidence that sevelamer reduced all-cause mortality, cardiovascular mortality, the frequency of symptomatic bone disease or health-related quality of life.