#4406 increase in hospitalized days after hyperkalemia-related reduction in raasi use: an observational study on cardiorenal patients in sweden and japan

Abstract Background and Aims Guidelines recommend renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at the maximum tolerated dose to achieve optimal treatment benefits in chronic kidney disease (CKD) and heart failure (HF). However, hyperkalemia (HK) is a barrier to achieving guideline-directed target dosing, with RAASi treatment often down-titrated or discontinued in patients who experience HK. Current international guidelines recommend novel oral anti-HK treatments to manage HK and facilitate optimization of RAASi therapy. The aim of this study was to describe the extent of RAASi reduction (down-titration or discontinuation) following an HK episode, and the associated change in inpatient days, in patients with cardiorenal disease in Sweden and Japan. Methods This observational study used data from health registers and hospital records in Sweden (national registers linked with health records from two large regions) and Japan (Medical Data Vision). Patients with an index HK episode, defined as ICD-10 code E87.5 (Japan and Sweden) or potassium >5.0 mmol/L (Sweden only), during March 2018 to July 2020 (Sweden) or May 2020 to February 2022 (Japan), with a prior diagnosis of CKD and/or HF, and RAASi use at index were included. RAASi classes included angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), and an angiotensin receptor-neprilysin inhibitor (ARNi). Patients were defined as having reduced or maintained their pre-HK RAASi treatment based on filled prescriptions, or lack thereof, within 90 (Japan) or 120 (Sweden) days before versus after the index HK episode. Propensity score matching (1:1) was applied to balance the cohorts who reduced versus maintained their pre-HK RAASi treatment on demographics, comorbidities, baseline medications (including RAASi), and inpatient days prior to index. The change in number of all-cause, CKD-, and HF-related inpatient days (per person-years of follow-up) was described from 6 months before to 6 months after the index HK episode. Results In total, 20,824 patients from Sweden and 7789 from Japan were included. The mean age was 76 (Sweden) and 74 (Japan) years; 57% and 65%, respectively, were male. In Sweden, 86% had CKD and 57% had HF; in Japan, 49% had CKD and 75% had HF. The most common RAASi classes in Sweden were ACEi (used by 49%), ARB (44%), and MRA (30%). In Japan, ARB was the most common class (73%), followed by MRA (28%), and ACEi (17%). Overall, 42% (n = 8716) of patients in Sweden and 38% (n = 2976) in Japan reduced their RAASi treatment after the HK episode. In the propensity score matched cohorts, the increase in number of all-cause inpatient days following an HK episode in those with reduced RAASi treatment was 18.2 days in Sweden (n = 6998) and 17.9 days in Japan (n = 2092) (Figure A and B). For reference, the increase in those who maintained their RAASi treatment was 9.4 and 8.5 days in Sweden and Japan, respectively. Similar patterns were observed for CKD- and HF-related inpatient days. Conclusion In clinical practice, an episode of hyperkalemia was often followed by reduced RAASi treatment. Reduced RAASi treatment was associated with a greater increase in the number of inpatient days, compared with maintained RAASi treatment. A better understanding of how guideline adherence can be increased to maintain RAASi treatment in patients experiencing HK is needed to achieve optimal treatment benefits in chronic kidney disease (CKD) and heart failure (HF).