#3303 SUBOPTIMAL EXTENT OF RAASI RE-INITIATION AFTER DISCONTINUATION FOLLOWING HYPERKALEMIA: AN OBSERVATIONAL STUDY OF CARDIORENAL PATIENTS IN THE US AND JAPAN
Authors: Kanda Eiichiro , Pollack Jr Charles , Rastogi Anjay , Lesén Eva , Agiro Abiy , Arnold Matthew , Chen Gengshi , Morita Naru , Järbrink Krister , Murohara Toyoaki 
Published: June 2023

Abstract

Background and Aims
Guidelines recommend renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at the maximal 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 and RAASi treatment is often compromised in patients who experience HK. Current international guidelines recommend novel oral anti-HK treatments to manage HK and facilitate RAASi therapy. This study assessed the extent of both temporary and longer-term discontinuation of RAASi following an HK episode, and the magnitude of RAASi re-initiation, in cardiorenal patients in the US and Japan.

Method
This observational study used data from hospital records and claims from the US (Optum's de-identified Market Clarity Data) and Japan (Medical Data Vision). Patients with an index HK event (ICD-10 code E87.5) during July 2019–September 2021 (US) or May 2020–February 2022 (Japan) with a prior diagnosis of CKD and/or HF and use of RAASi in the preceding 6 months were included. RAASi classes included angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor neprilysin inhibitors (ARNi). In patients who discontinued RAASi treatment following their index HK episode, duration of discontinuation was described within a time frame of 6 months from the date of discontinuation (those with &lt;6 months follow-up time were excluded). The RAASi dose prior to discontinuation versus at re-initiation was also assessed.

Results
In total, 25,963 patients from the US and 8,722 from Japan were included. The mean age was 68.3 (US) and 74.8 (Japan) years; 53% and 65% were male; and 30% and 12% of patients had a recorded history of HK prior to their index event. In the US, 85% filled a RAASi prescription in the 3 months prior to HK episode; the most common RAASi classes were ACEi (used by 46% of the overall cohort), ARB (27%), and MRA (19%). In Japan, 91% filled a RAASi prescription in the 3 months prior to HK episode; ARB was the most common (67%), followed by MRA (25%), and ACEi (16%). ARNi was used by &lt;5% of patients in the US and &lt;2% in Japan; it was not assessed further due to low patient numbers. Following the HK episode, ACEi/ARB were discontinued in 23–26% of patients, while MRA was discontinued in 33–46% (Table 1). In those who discontinued, re-initiation within 6 months occurred among 10–15% of patients in the US and among 6–8% of patients in Japan. In those who re-initiated, 17–37% of patients in the US and Japan had their dose reduced by &gt;25%.

Conclusion
In clinical practice, HK leads to discontinuation of RAASi treatment despite guidelines recommending maintained treatment. Re-challenge of RAASi treatment is uncommon and, when re-introduced, the dose is commonly reduced. These findings emphasize the need for improved guideline adherence in managing HK to facilitate continued RAASi therapy.