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Observational Study
. 2019 Jun 1;179(6):741-749.
doi: 10.1001/jamainternmed.2019.0045.

Cardiovascular Outcomes of Calcium-Free vs Calcium-Based Phosphate Binders in Patients 65 Years or Older With End-stage Renal Disease Requiring Hemodialysis

Julia Spoendlin  1 , Julie M Paik  2   3   4 , T Tsacogianis  1 , Seoyoung C Kim  1 , Sebastian Schneeweiss  1 , Rishi J Desai  1
Affiliations
Observational Study

Cardiovascular Outcomes of Calcium-Free vs Calcium-Based Phosphate Binders in Patients 65 Years or Older With End-stage Renal Disease Requiring Hemodialysis

Julia Spoendlin et al. JAMA Intern Med. .

Abstract

Importance: 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.

Objective: 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).

Exposures: 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.

Results: 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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Spoendlin reported receiving grants from Swiss National Science Foundation during the conduct of the study. Dr Kim reported receiving grants from Pfizer and grants from Bristol-Myers Squibb outside the submitted work. Dr Schneeweiss reported receiving personal fees from WHISCON LLC, personal fees and other support from Aetion, Inc, and grants from Bohringer-Ingelheim, Bayer, Vertex outside the submitted work. Dr Desai reported receiving grants from Merck, grants from Bayer, and grants from Vertex outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Weighted Kaplan-Meier Curves for Cardiovascular Events
Figure 2.
Figure 2.. Results of Subgroup Analyses for the Outcome Cardiovascular Events Primary As-Treated Analysis
Error bars indicate 95% CI. CV indicates cardiovascular.
See this image and copyright information in PMC

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