Real-World Use of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Heart Failure and Hypertension Initiating Sodium Zirconium Cyclosilicate: The Optimize Study

Introduction: Renin-angiotensin-aldosterone system inhibitors (RAASis) in patients (pts) with heart failure (HF) and hypertension (HTN) are associated with a reduced risk of death or disease progression, but increased risk of hyperkalemia (HK) with RAASis may lead to discontinuation and reduced benefit. This real-world study evaluated RAASi use patterns in pts who initiated sodium zirconium cyclosilicate (SZC) for HK. Methods: Adult (≥18 years) outpatients who initiated SZC (index date) while on RAASis were retrospectively identified from a large US claims database (Jan 2018 to Jun 2020). Analyses were conducted among all pts with HK and separately in those with HF or HTN. Outcomes included the proportion of pts with a new RAASi script (different or refill RAASi within 90 days of ending their index RAASi) and median time from index to RAASi discontinuation. A multivariable logistic regression assessed predictors of a new RAASi script among all pts. Results: Of 589 pts who initiated SZC during RAASi therapy (mean age 61.0 years, male 65%), 487 (83%) received a new RAASi script post index. In the HF (n=149) and HTN (n=538) cohorts, 120 (81%) and 446 (83%) received a new RAASi script. At index, the most common RAASi prescribed were ACE inhibitors (51%) and ARBs (42%). Among pts with a new RAASi script, median time from index to RAASi discontinuation was not reached ( Figure ), whereas in pts with no new RAASi script, median time from index to RAASi discontinuation was 29 days. Significant predictors of a new RAASi script (vs no new RAASi script) after SZC initiation were fewer prior hospitalizations (adjusted OR 0.77; 95% CI 0.60-0.98; P <0.05) and fewer ED visits (0.78; 0.63-0.97; P <0.05). Conclusions: Consistent with clinical trial findings, >80% of pts on RAASi therapy who initiated SZC for HK had a new RAASi script; similar results were observed in pts with HF or HTN. Pts with inpatient and ED visits may require additional follow-up care to encourage continuation of RAASi therapy.