title: Comparison of bisoprolol to a metoprolol CR/ZOK tablet for control of heart rate and blood pressure in mild-to-moderate hypertensive patients: the CREATIVE study.
abstract: This open-label study investigated the long action of bisoprolol compared with metoprolol CR/ZOK for controlling the mean dynamic heart rate (HR) and blood pressure (BP) in patients with mild-to-moderate primary hypertension. Patients from seven centers in China were treated with either bisoprolol 5 mg or metoprolol CR/ZOK 47.5 mg once daily for 12 weeks. The primary end points were the mean dynamic HR reduction and the mean dynamic diastolic BP (DBP) control in the last 4 h of the treatment period. Secondary end points included ambulatory monitoring of the BP and HR, safety and compliance. A total of 186 patients, with 93 patients in each group, were enrolled and analyzed. In the last 4 h of the treatment period, patients receiving bisoprolol demonstrated a significantly greater reduction in the mean dynamic HR compared with patients receiving metoprolol CR/ZOK (least squares means (LSmeans) of difference: -3.79 b.p.m.; 97.5% confidence interval (CI): -7.45, -0.14; P=0.0202). Furthermore, in the last 4 h of the treatment period, bisoprolol demonstrated non-inferiority vs. metoprolol CR/ZOK in lowering the mean dynamic DBP (LSmeans of difference: -1.00; 97.5% CI: -4.79, 2.78; P=0.5495). Bisoprolol further significantly lowered the 24-h mean ambulatory, mean daytime and mean nighttime HR. The overall adverse event rate was similar between the two groups. Noncompliance was reported in 3 (3.53%) and 6 (7.32%) patients in the bisoprolol and metoprolol CR/ZOK groups, respectively. In conclusion, bisoprolol provided superior dynamic HR reduction and non-inferior dynamic BP reduction vs. metoprolol CR/ZOK in patients with mild-to-moderate hypertension. No new safety concerns were found.
authors.affiliation: Cardiovascular Department, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: The Second Hospital, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Zhou
authors.affiliation: The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China.
authors.forename: Xinjuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Zhejiang Province People's Hospital, Hangzhou, China.
authors.forename: Baiming
authors.initials: B
authors.lastname: Qu
authors.affiliation: The Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Lin
authors.affiliation: Merck Serono China, Beijing, China.
authors.forename: Tianrong
authors.initials: T
authors.lastname: Ma
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017298:Bisoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D003692:Delayed-Action Preparations; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D008790:Metoprolol; D017298:Bisoprolol