Phosphate Binders and Mortality: There Is a Need for More Evidence.

To the Editor: Mineral and bone disorder of chronic kidney disease has been linked to mortality. The meta-analysis by Palmer et al concluded that phosphate binders, whether calcium based or non–calcium based, did not reduce all-cause mortality compared to placebo. However, all-cause mortality was lower with sevelamer compared with calcium-based binders, which appears to have been driven by a single long-term study. Another network meta-analysis of randomized trials demonstrated higher all-cause mortality associated with calcium-based binders compared with non–calcium-based binders, specifically when compared to sevelamer. As the authors note, it is difficult to say whether the difference in mortality is due to harmful effects of calcium-based binders or beneficial effects of sevelamer. These results indicate the need for trials of sufficient power and duration to address whether phosphate binders reduce mortality and, if they do, whether there is a difference between different types of binders. In all 3 recent meta-analyses, calcium acetate and calcium carbonate have been lumped together as calcium-based binders. Calcium carbonate contains higher elemental calcium than calcium acetate. Multiple treatment comparisons used to inform the National Institute for Health and Care Excellence (NICE) guideline showed calcium acetate to be as effective as any other binder at various time points (3, 6, and 12 months). The health economic model reflected a probable survival benefit of non–calcium-based binders, but this came at a great expense. The incremental cost-effectiveness ratio for sevelamer was £90,000 per quality-adjusted life-year compared to £8,000 for calcium acetate when used as a first-line binder. Thus, calcium acetate was recommended as first-line treatment. Until sevelamer is available at a significantly lower price, it would be difficult to justify using it as a first-line phosphate binder.