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Observational Study
. 2023 Jan 19;24(1):18.
doi: 10.1186/s12882-022-03054-5.

Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia

Eiichiro Kanda  1 , Anjay Rastogi  2 , Toyoaki Murohara  3 , Eva Lesén  4 , Abiy Agiro  5 , Matthew Arnold  6 , Gengshi Chen  7 , Toshitaka Yajima  8 , Krister Järbrink  4 , Charles V Pollack Jr  9
Affiliations
Observational Study

Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia

Eiichiro Kanda et al. BMC Nephrol. .

Abstract

Background: Hyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD.

Methods: This observational study utilized data from hospital records, claims, and health registers from the US (Optum's de-identified Market Clarity Data) and Japan (Medical Data Vision). Included patients had an index episode of HK between July 2019 and September 2021 (US), or May 2020 and September 2021 (Japan), with prior diagnosis of HF or CKD (stage 3 or 4), and RAASi use. Risk of a cardiorenal composite outcome (HF emergency visit, HF hospitalization, or progression to end-stage kidney disease) was determined in patients who discontinued RAASi, down-titrated their dose by > 25%, or maintained or up-titrated their dose following the HK episode.

Results: A total of 15,488 and 6020 patients were included from the US and Japan, respectively. Prior to the episode of HK, 59% (US) and 27% (Japan) of patients had achieved > 50% target RAASi dose. Following the episode of HK, 33% (US) and 32% (Japan) of patients did not fill a new RAASi prescription. Risk of the cardiorenal outcome at 6 months was higher in patients who discontinued or down-titrated versus maintained or up-titrated RAASi treatment both in the US (17.5, 18.3, and 10.6%; p < 0.001) and in Japan (19.7, 20.0, and 15.1%; p < 0.001).

Conclusion: HK-related RAASi discontinuation or down-titration was associated with higher risk of cardiorenal events versus maintained or up-titrated RAASi.

Keywords: Chronic kidney disease; Guideline-directed medical therapy; Heart failure; Hyperkalemia; Potassium binder.

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Conflict of interest statement

E.K. declares no competing interests.

A.R. has received institutional support relating to research grants from Alnylam Pharmaceuticals, AstraZeneca, Bayer, Gilead, GSK, Idorsia Pharmaceuticals Ltd., the National Institutes of Health, Novo Nordisk, Kadmon Corporation (LLC), Omeros Inc., Otsuka Pharmaceuticals, Palladio Biosciences, Pfizer, Protalix Biotherapeutics Ltd., Reata Pharmaceuticals, Regulus Therapeutics, Summit Therapeutics, and Sanofi; consulting fees or support for participation in advisory boards from Akebia, Amgen, Ardelyx, AstraZeneca, Aurinia, Baxter, Chiesi Global Inc., Chinook Therapeutics, Fresenius Medical Care, GSK, Otsuka, Relypsa, Sanofi, Tricida, and Vifor Pharma Inc.; speaker fees from Amgen, AstraZeneca, Aurinia, Bayer, Baxter, Fresenius Medical Care, Genzyme/Sanofi, Janssen, National Kidney Foundation, Vifor Pharma Inc., and Natera; provision of expert testimony from Quinn Emanuel Urquhart & Sullivan (LLP), and Bowman and Brooke Attorneys at Law; and, for attending meetings and/or travel from all of the above.

T.M. has received honoraria for educational materials from AstraZeneca, Lilly, and Boehringer Ingelheim Japan.

M.A. is an employee of AstraZeneca.

E.L., A.A., G.C., T.Y., and K.J. are employees of, and hold stock/stock options in, AstraZeneca.

C.V.P. has received consultancy fees from AstraZeneca.

Figures

Fig. 1
Fig. 1
Attainment of guideline-recommended RAASi dose in (a) the US and (b) Japan. HK hyperkalemia, mo month, RAASi renin-angiotensin-aldosterone system inhibitor
Fig. 2
Fig. 2
RAASi change following an HK episode in (a) the US and (b) Japan. ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, ARNi angiotensin receptor-neprilysin inhibitor, HK hyperkalemia, MRA mineralocorticoid receptor antagonist, RAASi renin-angiotensin-aldosterone system inhibitor
Fig. 3
Fig. 3
Risk of cardiorenal composite outcome by change in RAASi treatment following HK episode: (a) the US, (b) Japan. CI confidence interval, HK hyperkalemia, RAASi renin-angiotensin-aldosterone system inhibitor. P-value for the differences between the groups: US, p < 0.001; Japan, p < 0.001
See this image and copyright information in PMC

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