title: Beneficial Effect on Surrogate Markers of Heart Failure with Bisoprolol Up-Titration to Recommended Targets in Korean Patients with Heart Failure and Left Ventricular Systolic Dysfunction.
abstract: BACKGROUND
  The objective of this study was to establish the benefit of bisoprolol up-titration toward recommended dosage targets, versus lower-dose maintenance, in heart failure (HF) patients with systolic dysfunction.
  
  
  METHODS
  Korean HF patients received bisoprolol 1.25 mg/day, incrementally up-titrated toward 10 mg/day in the absence of contraindications. After 26 weeks' treatment, patients were grouped as low-dose (<3.75 mg/day) or high-dose (≥3.75 mg/day). Primary endpoint was change in serum N-terminal probrain natriuretic peptide (NT-proBNP). Other markers of HF were also evaluated.
  
  
  RESULTS
  159 of 180 enrolled patients were evaluable. After 16 weeks' follow-up, there were 52 and 107 patients in the low- and high-dose groups respectively. Mean bisoprolol dosage was 5.4 mg/day; 24% of patients achieved target (10 mg/day). Mean logNT-proBNP significantly decreased in both groups, with no significant difference in the magnitude of change between groups. Mean heart rate (HR) and blood pressure decreased significantly in both groups, but only HR showed a significantly greater change in high-dose versus low-dose patients. In both groups, mean left ventricular (LV) end-systolic and end-diastolic dimensions were significantly decreased and mean LV ejection fraction was significantly improved. Mean 6-min walk test distances improved in both groups (significant in low-dose patients only). Functional class improvement was observed in both low- and high-dose patients. No patients were rehospitalized due to aggravated HF.
  
  
  CONCLUSIONS
  In HF patients with systolic dysfunction, any bisoprolol dose is beneficial, but an attempt to up-titrate toward guideline-recommended dosages offers additional benefit in terms of restoration of LV systolic function and remodeling.
authors.affiliation: Department of Cardiovascular Medicine, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwasung, Republic of Korea.
authors.forename: Seong Woo
authors.identifier: http://orcid.org/0000-0002-0678-223X
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Cardiovascular Medicine, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwasung, Republic of Korea.
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Department of Cardiovascular Medicine, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwasung, Republic of Korea.
authors.forename: Kyu-Hyung
authors.initials: KH
authors.lastname: Ryu
authors.affiliation: Department of Cardiovascular Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.
authors.forename: Hyun-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Cardiovascular Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.
authors.forename: Sung Hea
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Anam Hospital, Korea University Cardiovascular Center, Seoul, Republic of Korea.
authors.forename: Wan Joo
authors.initials: WJ
authors.lastname: Shim
authors.affiliation: Department of Internal Medicine, School of Medicine, Kosin University, Busan, Republic of Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cha
authors.affiliation: Department of Cardiovascular Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Cardiology Division, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Byung-Su
authors.initials: BS
authors.lastname: Yoo
authors.affiliation: Department of Cardiology in Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
authors.forename: Jun-Hyung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Kyung-Kuk
authors.initials: KK
authors.lastname: Hwang
authors.affiliation: Department of Cardiovascular Medicine, Uijeongbu ST Mary's Hospital, The Catholic University of Korea, Eujeongboo, Republic of Korea.
authors.forename: HuiKyung
authors.initials: H
authors.lastname: Jeon
authors.affiliation: Cardiology Division, Gachon University Gil Medical Center, Incheon, Republic of Korea.
authors.forename: Mi-Seung
authors.initials: MS
authors.lastname: Shin
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D015415:Biomarkers / Q000097:blood; D017298:Bisoprolol / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods*; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020127:Recovery of Function; D056910:Republic of Korea; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D017298:Bisoprolol
keywords: Bisoprolol; N-terminal probrain natriuretic peptide; NT-proBNP; beta-blocker; heart failure; left ventricular systolic dysfunction