Relevant adverse events and drug discontinuation of sacubitril/valsartan in a real-world Japanese cohort: REVIEW-HF registry

Shingo Matsumoto; John J V McMurray; Takahito Nasu; Shunsuke Ishii; Nobuyuki Kagiyama; Keisuke Kida; Wataru Fujimoto; Atsushi Kikuchi; Takeshi Ijichi; Tatsuhiro Shibata; Takanori Ikeda; Koshiro Kanaoka

doi:10.1016/j.jjcc.2023.11.005

Relevant adverse events and drug discontinuation of sacubitril/valsartan in a real-world Japanese cohort: REVIEW-HF registry

J Cardiol. 2023 Nov 22:S0914-5087(23)00276-9. doi: 10.1016/j.jjcc.2023.11.005. Online ahead of print.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Faculty of Medicine, Tokyo, Japan; British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. Electronic address: shingomatsumoto0606@gmail.com.
² British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
³ Division of Cardiology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan.
⁴ Department of Cardiovascular Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
⁵ Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Digital Health and Telemedicine, R&D, Tokyo, Japan.
⁶ Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
⁷ Department of Cardiology, Hyogo Prefectural Awaji Medicine Center, Hyogo, Japan.
⁸ Division of Cardiology, Osaka General Medical Center, Osaka, Japan.
⁹ Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan.
¹⁰ Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
¹¹ Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Faculty of Medicine, Tokyo, Japan.
¹² Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Osaka, Japan; Department of Cardiovascular Medicine, Nara Medical University, Nara, Japan.

PMID: 38000538
DOI: 10.1016/j.jjcc.2023.11.005

Abstract

Background: The characteristics, tolerability, and outcomes in patients with heart failure (HF) who are treated with sacubitril/valsartan remain unclear in Japan.

Methods: We conducted a nationwide multicenter study to evaluate the features and outcomes of patients newly prescribed sacubitril/valsartan for the management of HF. We analyzed adverse events (AEs) related to sacubitril/valsartan at 3 months, which were defined as hypotension, worsening renal function, hyperkalemia, and angioedema. Additionally, the association between AEs and outcomes was examined.

Results: Among 993 patients, the mean age was 70 years and 291 (29.3 %) were female, and 22.8 % had left ventricular ejection fraction ≥50 %. Of them, 20.8 % had systolic blood pressure (sBP) <100 mmHg, and 19.5 % had estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m² at baseline, which were the populations excluded from the eligibility in landmark trials. AEs related to sacubitril/valsartan were observed in 22.5 % of the patients at 3 months. Overall, 22.6 % of patients discontinued sacubitril/valsartan, and hypotension was the most common event leading to drug discontinuation. After adjustment, patients who had worse HF symptoms (New York Heart Association III or IV), sBP <100 mmHg, and eGFR <30 ml/min/1.73 m² were associated with a higher risk of AEs related to sacubitril/valsartan. Additionally, patients experiencing AEs had a higher risk of cardiovascular death or HF hospitalization than those who did not.

Conclusion: In Japan, sacubitril/valsartan was also prescribed to patients not eligible for landmark trials, and AEs were observed at a relatively high rate from soon after treatment initiation. Physicians should closely monitor patients for these events, especially in patients anticipated to have a higher risk of AEs.

Keywords: Adverse event; Asia; Heart failure with preserved ejection fraction; Heart failure with reduced ejection fraction; Sacubitril/valsartan.