The noncalcium phosphate binder sevelamer has no advantage over the calcium-based binder calcium acetate with respect to cardiovascular (CV) events and death in older patients on hemodialysis (HD), new research suggests.

Using data from the US Renal Data System from May 1, 2012, to December 31, 2013, a team led by Rishi J. Desai, MS, PhD, of Brigham and Women’s Hospital in Boston conducted an observational cohort study of patients aged 65 years or older initiating HD and phosphate binder therapy. A total of 2639 patients received sevelamer and 2065 received calcium acetate. The investigators found no significant difference in the risks for CV events and death between the 2 groups, according to a report in JAMA Internal Medicine. The sevelamer group experienced 458 CV events per 1000 person-years and the calcium acetate group suffered 464 per 1000 person-years. The sevelamer and calcium acetate groups experienced 208 and 217 deaths per 1000 person-years, respectively. The risks for CV events (nonfatal and fatal) and all-cause mortality were 4% lower for sevelamer users. Subgroup analyses by age and sex yielded similar results.

The team adjusted for 78 potential confounders, most importantly serum calcium and phosphorus levels, CV disease, concomitant medications, socioeconomic status, and health care use.

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“The results of this observational cohort study do not suggest that sevelamer is associatedwith superior cardiovascular safety or survival compared with calcium acetate in a routine care setting of patients 65 years or older with ESRD requiring maintenance HD in the United States,” the authors concluded.

The 2017 update of the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline suggested restricting use of calcium-based phosphate binders in patients with end-stage renal disease based on results from 3 randomized controlled trials (RCTs). But these trials were graded as methodologically weak, the investigators explained.

“This null result suggests that any potential increased safety of sevelamer compared with calcium-based phosphate binders on cardiovascular events observed in previous small trials with nonrepresentative populations may not translate into routine clinical practice; this observation questions the high cost incurred to national budgets by use of sevelamer and calls for well-designed randomized clinical trials,” Dr Desai and his colleagues wrote.

The new study “provides evidence that calcium-based phosphate binders are unlikely to increase cardiovascular events or mortality to a meaningful degree compared with sevelamer, at least as initial therapy and up to 3 years of follow-up,” Bryan R. Kestenbaum, MD, MS, and Ian H. de Boer, MD, MS, of Kidney Research Institute in Seattle, commented in an accompanying editorial.

The editorialists noted that the study lacked information on phosphate binder doses, which is a limitation.

“The proposed mechanism by which calcium-based binders are suspected to cause harm is by contributing to calcium accumulation in soft tissues in the setting of impaired calcium excretion,” they wrote. “Dose assessment and longer follow-up in future studies could help shed light on this question.”


Spoendlin J, Paik JM, Tsacogianis T, et al. Cardiovascular outcomes of calcium-free vs calcium-based phosphate binders in patients 65 years or older with end-stage renal disease requiring hemodialysis. JAMA Intern Med. doi:10.1001/jamainternmed.2019.0045 (Published online May 6, 2019.)

Kestenbaum BR and de Boer IH. Comparative safety of phosphate binders without proven efficacy—How did we get here? JAMA Intern Med. doi:10.1001/jamainternmed.2019.0043 (Published online May 6, 2019.)