Suki WN et al. (2007) Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int 72: 1130–1137

Hyperphosphatemia and hypercalcemia are independently associated with an increased risk of cardiovascular calcification and mortality in patients on dialysis. Sevelamer hydrochloride has the potential to reduce serum phosphorus levels without promoting arterial calcification (which can result from use of calcium-based oral phosphate binders [OPBs]) and could contribute to lower all-cause mortality.

The Dialysis Clinical Outcomes Revisited trial randomized 2,103 prevalent hemodialysis patients to sevelamer or a calcium-based OPB; 1,068 patients completed the study (mean treatment time approximately 19 months). Adverse events that resulted in discontinuation were mainly hypercalcemia-related in the OPB group and gastrointestinal in the sevelamer group.

In the entire group, all-cause and cause-specific (e.g. cardiovascular and infection-related) mortality rates were not significantly different between the two treatments; the study was not, however, adequately powered to detect cause-specific differences. Kaplan–Meier analysis indicated a survival improvement with sevelamer in patients who participated in the trial for 2 years or more (time–treatment interaction; P = 0.02).

Sevelamer was associated with a significant reduction in all-cause mortality in patients over 65 years of age (P = 0.02 for comparison with OPB treatment); in younger patients, mortality was slightly but not significantly higher with sevelamer. Sevelamer also reduced the frequency of hospitalization among older patients. These findings could be a function of the greater pre-existing calcification burden in older patients on hemodialysis, which could more rapidly facilitate the effects of oral calcium on mortality.