Maintained renin–angiotensin–aldosterone system inhibitor therapy with sodium zirconium cyclosilicate following a hyperkalaemia episode: a multi-country cohort study

Abstract Background This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin–angiotensin–aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the US, Japan, and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder. Methods Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the No K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus No K+ binder cohorts. Results The PS-matched SZC cohort included 565 (US), 776 (Japan), and 56 (Spain) patients; the No K+ binder cohort included 2068, 2629, and 203 patients, respectively. At 6 months, 68.9% (US), 79.9% (Japan), and 69.6% (Spain) in the SZC cohorts, versus 53.1% (US), 56.0% (Japan), and 48.3% (Spain) in the No K+ binder cohorts, had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus No K+ binder cohort was 2.56 (95% confidence interval 1.92–3.41; P < 0.0001). Conclusions In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment.