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    Although bisoprolol has been established to prevent heart failure (HF), finding the optimal dose remains a challenge. It is crucial to understand the distribution of bisoprolol plasma concentration (Bis-PC) and association with outcomes. This was a single-center observational study in 114 HF patients under once-daily bisoprolol. After obtaining trough Bis-PC, patients were followed-up for 1 year. The primary endpoint was worsening of HF. Patients were divided according to the tertiles of Bis-PC. In multivariate logistic regression analysis, independent predictors of high Bis-PC (1st tertile: ≥ 5.38 ng/mL) were age, eGFR, and bisoprolol dose. The cumulative incidence rates of the primary endpoint were 10.5%/13.2%/26.3% in low/middle/high Bis-PC categories, respectively (log rank test, p = 0.087). Bis-PC was independently associated with the primary endpoint (hazard ratio [HR], 1.19 [per ng/mL], 95% CI 1.03-1.36). In subgroups, high Bis-PC was independently associated with the primary endpoint in elderly (HR 6.32, 95% CI 1.34-29.83) and HF with preserved ejection fraction (HFpEF) (HR 3.52, 95% CI 1.06-11.70). Bis-PC was increased by age and renal dysfunction, and high Bis-PC was associated with worsening of HF in elderly and HFpEF patients. Care should be taken to avoid overdose. Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.


    Takuto Arita, Shinya Suzuki, Yuko Kato, Hiroto Kano, Junji Yajima, Shunsuke Matsuno, Takayuki Otsuka, Hiroaki Semba, Tokuhisa Uejima, Yuji Oikawa, Kazuyuki Nagashima, Naoharu Yagi, Koichi Sagara, Gen Tanabe, Takeshi Yamashita. Association between bisoprolol plasma concentration and worsening of heart failure: (CVI ARO 6). Drug metabolism and pharmacokinetics. 2020 Apr;35(2):228-237

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    PMID: 32044255

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