Abstract

Abstract Background and Aims Guidelines recommend renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at the maximum tolerated dose in patients with chronic kidney disease (CKD) and/or heart failure (HF). Hyperkalaemia (HK) may be a barrier to achieving guideline-directed targets, with RAASi treatment often being down-titrated or discontinued in patients who experience HK. Guidelines suggest targeted anti-HK management with potassium binders to facilitate maintained RAASi. In patients with CKD and/or HF, we describe the extent of HK-related RAASi reduction. To provide clinicians with a sense of magnitude of impact, we estimate the ‘number needed to treat’ (NNT) to avoid a first hospitalisation if RAASi had been maintained at prior dose. Method This observational cohort study used contemporary data from four European countries (Germany, Spain, Sweden, UK). The population included non-dialysis patients diagnosed with CKD and/or HF who had an index HK episode (defined as a recorded HK diagnosis or potassium >5.0 mmol/L) while on RAASi therapy. Patients were defined as having reduced (down-titrated or discontinued) vs maintained RAASi treatment based on their most recent prescriptions, or lack thereof, within 120 days before vs after the index HK episode. Those who died within the first 120 days post index HK were excluded to avoid misclassification bias. Propensity score (PS) matching was applied to balance the groups on baseline characteristics. Patients were followed for 6 months after the index HK event. The risk of an all-cause hospitalisation in patients who reduced vs maintained RAASi was assessed at 6 months using the Kaplan–Meier method. The NNT framework was applied to estimate the number of patients who would need to have maintained instead of reduced their RAASi therapy to avoid a firsthospitalisation during this period. Results By Dec 2023, the study includes a total of 33,009 patients with CKD and/or HF from Germany (N = 11,199), Spain (N = 4406) and Sweden (N = 17,404); UK data extraction is in progress. Presence of CKD at baseline was similar across countries (77–85%), while HF was more common in Germany (70%) and Sweden (55%) than in Spain (18%). After the index HK episode, RAASi therapy was reduced (down-titrated or discontinued) in 25–44% of patients. Following PS matching (available from Spain and Sweden), the 6-month risk of at least one all-cause hospitalisation was consistently higher in those with reduced relative to maintained RAASi (Table). Data suggest that a first hospitalisation within 6 months could potentially have been avoided if 20–24 patients had maintained instead of reduced their RAASi. Conclusion Despite current guidelines recommending targeted anti-HK management with potassium binders to facilitate maintained RAASi treatment, HK is still associated with frequent down-titration or discontinuation of RAASi therapy in clinical practice. Following PS matching and using the NNT framework, our data suggest a potential for avoiding a firsthospitalisation, even within a short time frame, by increasing guideline adherence to maintain instead of reducing RAASi after a HK episode.

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