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

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.