TY - JOUR
T1 - Risk–Benefit Balance of Renin–Angiotensin–Aldosterone Inhibitor Cessation in Heart Failure Patients with Hyperkalemia
AU - Kohsaka, Shun
AU - Okami, Suguru
AU - Morita, Naru
AU - Yajima, Toshitaka
N1 - Funding Information:
S.K. reports investigator-initiated grant funding from Daiichi Sankyo and personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, and Pfizer. S.O., N.M., and T.Y. are employees of AstraZeneca K.K.
Funding Information:
This research was funded by AstraZeneca.
Funding Information:
The authors thank Masatsugu Arai, Hyosung Kim, Takashi Kikuchi, Rashad Mogalli, and Tomoko Ishizu from AstraZeneca for their assistance with the statistical analysis, valuable comments, and logistical support as well as Masafumi Okada, ZhenZhen Fang, Yiyun Lin, and all of the project members from IQVIA Solutions, K.K. for providing technical and editorial support, including data analysis, under the guidance of the authors. The authors also wish to thank Edanz, Japan, for providing medical writing support on the initial draft of this paper, which was funded by AstraZeneca K.K., Japan, through EMC K.K., Japan, in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ; accessed on 1 August 2022).
Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - Background: Whether to continue renin–angiotensin–aldosterone system inhibitor (RAASi) therapy in patients with hyperkalemia remains a clinical challenge, particularly in patients with heart failure (HF), where RAASis remain the cornerstone of treatment. We investigated the incidence of dose reduction or the cessation of RAASis and evaluated the threshold of serum potassium at which cessation alters the risk–benefit balance. Methods: This retrospective analysis of a Japanese nationwide claims database investigated treatment patterns of RAASis over 12 months after the initial hyperkalemic episode. The incidences of the clinical outcomes of patients with RAASi (all ACEi/ARB/MRA) or MRA-only cessation (vs. non-cessation) were compared via propensity score-matched patients. A cubic spline regression analysis assessed the hazard of death resulting from treatment cessation vs. no cessation at each potassium level. Results: A total of 5059 hyperkalemic HF patients were identified; most received low to moderate doses of ACEis and ARBs (86.9% and 71.5%, respectively) and low doses of MRAs (76.2%). The RAASi and MRA cessation rates were 34.7% and 52.8% at 1 year post-diagnosis, while the dose reduction rates were 8.4% and 6.5%, respectively. During the mean follow-up of 2.8 years, patients who ceased RAASi or MRA therapies were at higher risk for adverse outcomes; cubic spline analysis found that serum potassium levels of <5.9 and <5.7 mmol/L conferred an increased mortality risk for RAASi and MRA cessation, respectively. Conclusions: Treatment cessation/dose reduction of RAASis are common among HF patients. The risks of RAASi/MRA cessation may outweigh the benefits in patients with mild to moderate hyperkalemia.
AB - Background: Whether to continue renin–angiotensin–aldosterone system inhibitor (RAASi) therapy in patients with hyperkalemia remains a clinical challenge, particularly in patients with heart failure (HF), where RAASis remain the cornerstone of treatment. We investigated the incidence of dose reduction or the cessation of RAASis and evaluated the threshold of serum potassium at which cessation alters the risk–benefit balance. Methods: This retrospective analysis of a Japanese nationwide claims database investigated treatment patterns of RAASis over 12 months after the initial hyperkalemic episode. The incidences of the clinical outcomes of patients with RAASi (all ACEi/ARB/MRA) or MRA-only cessation (vs. non-cessation) were compared via propensity score-matched patients. A cubic spline regression analysis assessed the hazard of death resulting from treatment cessation vs. no cessation at each potassium level. Results: A total of 5059 hyperkalemic HF patients were identified; most received low to moderate doses of ACEis and ARBs (86.9% and 71.5%, respectively) and low doses of MRAs (76.2%). The RAASi and MRA cessation rates were 34.7% and 52.8% at 1 year post-diagnosis, while the dose reduction rates were 8.4% and 6.5%, respectively. During the mean follow-up of 2.8 years, patients who ceased RAASi or MRA therapies were at higher risk for adverse outcomes; cubic spline analysis found that serum potassium levels of <5.9 and <5.7 mmol/L conferred an increased mortality risk for RAASi and MRA cessation, respectively. Conclusions: Treatment cessation/dose reduction of RAASis are common among HF patients. The risks of RAASi/MRA cessation may outweigh the benefits in patients with mild to moderate hyperkalemia.
KW - heart failure
KW - hyperkalemia
KW - mineralocorticoid receptor antagonists
KW - renin–angiotensin–aldosterone system inhibitors
KW - risk–benefit
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U2 - 10.3390/jcm11195828
DO - 10.3390/jcm11195828
M3 - Article
AN - SCOPUS:85139797629
SN - 2077-0383
VL - 11
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 19
M1 - 5828
ER -