The Association of Heart Failure and Edema Events between Patients Initiating Sodium Zirconium Cyclosilicate or Patiromer

Key Points One previous study using claims data reported signals for higher hospitalizations for heart failures and severe edema in patients prescribed a potassium binder using sodium exchange. In this study, sodium zirconium cyclosilicate use was associated with increased risk of prespecified encounters of hospitalizations for heart failure and major edema encounters. Our findings highlight the need to weigh the benefits and risks of sodium zirconium cyclosilicate and patiromer in routine clinical practice. Background Sodium zirconium cyclosilicate (SZC) and patiromer (PAT) are potassium binders that differ by exchange ion, sodium, and calcium, respectively. There are limited data on whether using sodium exchange could affect the risks of hospitalizations for heart failure (HHF) or severe edema in patients with hyperkalemia. The goal of this study was to assess the occurrence rates of prespecified major encounters potentially related to electrolyte-/fluid-related imbalances (including HHF, edema) among new users of PAT or SZC. Methods Using Cerner Real World Data, we conducted a retrospective cohort study among adults (≥18 years) who were newly initiated on SZC or PAT between June 1, 2018, and December 31, 2021. Based on baseline demographic and clinical characteristics, one PAT initiator was propensity score matched with two SZC initiators. Primary outcomes were any HHF, primary HHF, major edema encounter, or death. Cox proportional hazard regression models were used to estimate the association between SZC or PAT use and each outcome in the overall population and subgroups with/without prior heart failure (HF). Results The final cohort included 9929 PAT initiators matched to 19, 849 SZC initiators. The mean age was 66 years; about 50% had a history of CKD stages 3–5 and 34% a history of HF. Incidence rates were significantly higher in the SZC cohort when compared with the PAT cohort for all outcomes. Risks of HHF (any/primary) (adjusted hazard ratios [HRs], 1.373; 95% confidence interval [CI], 1.337 to 1.410), major edema encounter (HR, 1.330; 95% CI, 1.298 to 1.363), and death (HR, 1.287; 95% CI, 1.255 to 1.320) were also significantly higher in the SZC cohort compared with the PAT cohort ( P < 0.05). These findings were consistent among subgroups with/without prior HF. Conclusions SZC use (versus PAT) was associated with an increased risk of prespecified encounters that were potentially sodium-/fluid-related, including among patients with/without preexisting HF.