Cardiorenal risks increase following discontinuation or downtitration of renin-angiotensin-aldosterone system inhibitors (RAASi) due to hyperkalemia in patients with heart failure and/or stage 3-4 chronic kidney disease (CKD), investigators report.

Eiichiro Kanda, MD, PhD, MPH, of Kawasaki Medical School in Okayama, Japan, and colleagues identified 15,488 and 6020 patients who experienced a hyperkalemia episode during 2019-2021 from health registers in the United States (Optum’s de-identified Market Clarity Data) and Japan (Medical Data Vision), respectively. Before the hyperkalemia episode, 59% and 27% of patients from the US and Japan, respectively, had achieved more than 50% of the target RAASi dose. After the hyperkalemia episode, 33% and 32%, respectively, did not fill a new RAASi prescription, and 7% and 6%, respectively, downtitrated at least 1 RAASi dose by more than 25%. Only 1% of patients initiated a novel potassium binder such as sodium zirconium cyclosilicate or patiromer following hyperkalemia.

The cardiorenal composite outcome occurred within 6 months in significantly higher proportions of patients in the US (17.5% and 18.3% vs 10.6%) and in Japan (19.7% and 20.0% vs 15.1%) who discontinued or downtitrated RAASi versus maintained/uptitrated RAASi, respectively. In adjusted analyses, the risk for the cardiorenal composite outcome was a significant 55% and 24% higher among patients in the US and Japan, respectively, who discontinued vs maintained their RAASi treatment, Dr Kanda’s team reported in BMC Nephrology. The composite outcome included a heart failure hospitalization or emergency department visit or progression to end-stage kidney disease. RAASi included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, and mineralocorticoid receptor antagonists (except for finerenone).

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“These data emphasize the importance of RAASi optimization following an episode of [hyperkalemia] and the need for targeted treatment of [hyperkalemia] to facilitate optimal RAASi management,” according to Dr Kanda’s team.

Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.


Kanda E, Rastogi A, Murohara T, et al. Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia. BMC Nephrol 24(1):18. doi:10.1186/s12882-022-03054-5