Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age

Abstract

Importance: Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use.

Objective: To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age.

Design, setting, and participants: Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level.

Exposure: Dispensed sodium polystyrene sulfonate in an outpatient setting.

Main outcomes and measures: The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription.

Results: From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury.

Conclusions and relevance: The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Carrero reported receiving grants from AstraZeneca and Vifor Pharma. Dr Tangri reported receiving personal fees from Tricida Inc, and Otsuka and reported receiving grants and personal fees from AstraZeneca. Dr Komenda reported being chief medical officer at Quanta Dialysis Technologies. Dr Sood reported receiving a grant from Otsuka. No other disclosures were reported.

Figures

Figure.. 30-Day Probability of Gastrointestinal (GI) Injury Requiring Hospitalization or Emergency Department Visit Associated With Sodium Polystyrene Sulfonate Use Compared With Nonuse

Results presented are for the matched analysis of sodium polystyrene sulfonate users to nonusers on the logit of the high-dimensional propensity score (±0.2 of the standard deviation) and the following: age, sex, diabetes, congestive heart failure, prior acute kidney injury, chronic dialysis, history of hyperkalemia, previous nephrologist visit, medication use (β-blocker or renin-angiotensin-aldosterone system blockade), and index date (within 1 year). Additional adjustment was for place of residence.