Is the calcium-free phosphate binder sevelamer carbonate associated with superior cardiovascular end points compared with calcium acetate in patients 65 years or older with end-stage renal disease who are undergoing dialysis?
In this cohort study of data from 2639 patients 65 years or older with end-stage renal disease in the United States Renal Data System, a similar risk of cardiovascular events and death between sevelamer and calcium acetate initiators was noted after adjusting for 78 potential confounders, including serum calcium and phosphorous levels.
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.
Guidelines restricting use of calcium-based phosphate binders in all patients with end-stage renal disease owing to their potential contribution to increased cardiovascular risk shifted prescribing from calcium acetate toward the costlier sevelamer carbonate products.
To compare cardiovascular events and mortality between patients with end-stage renal disease (ESRD) undergoing hemodialysis receiving sevelamer vs calcium acetate in real-world practice.
Design, Setting, and Participants
An observational cohort study was conducted using the United States Renal Data System linked to Medicare claims data (May 1, 2012, to December 31, 2013). Data analysis was performed from October 2017 to September 2018. Participants included patients 65 years or older with ESRD within 180 days after starting hemodialysis (sevelamer, 2647; calcium acetate, 2074).
New use of sevelamer (calcium-free phosphate binder) vs calcium acetate (calcium-based phosphate binder).
Main Outcomes and Measures
Hazard ratios (HRs) with 95% CIs were estimated for fatal or nonfatal cardiovascular events (myocardial infarction or ischemic stroke: primary outcome) and all-cause mortality (secondary outcome) using Cox proportional hazards regression with fine stratification on the propensity score to control for potential confounders, including phosphorus and calcium levels.
After propensity score weighting, 2639 patients initiating sevelamer treatment (1184 men [44.9%]; mean [SD] age, 75.6 [6.9] years) and 2065 patients initiating calcium acetate treatment (930 men [45.0%]; mean [SD] age, 75.5 [7.1] years) were included in the analysis. Crude incidence rates (IRs) for cardiovascular events of 458 per 1000 person-years for sevelamer and 464 per 1000 person-years for calcium acetate were observed. After propensity score fine-stratification weighting, HRs of 0.96 (95% CI, 0.84-1.10) for cardiovascular events were observed. Results were consistent within subgroups of age (<75 y: primary outcome, HR, 1.02; 95% CI, 0.85-1.24; vs ≥75 years: primary outcome, HR, 0.83; 95% CI, 0.69-1.01) and sex (primary outcome in men: HR, 1.02; 95% CI, 0.83-1.26).
Conclusions and Relevance
The results of the study do not suggest increased cardiovascular safety of sevelamer in the routine clinical practice of patients with ESRD compared with calcium acetate; this study’s findings suggest that well-designed, long-term, randomized clinical trials are needed.
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Spoendlin J, Paik JM, Tsacogianis T, Kim SC, Schneeweiss S, Desai RJ. 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. Published online May 06, 2019. doi:10.1001/jamainternmed.2019.0045
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