Equal Efficacy and Improved Tolerability with 50 mg Controlled-Release Metoprolol Compared with 100 mg Conventional Metoprolol in Hypertensive Patients.

: The clinical efficacy and tolerability of 50 mg of a new controlled-release formulation of metoprolol (metoprolol CR) was compared with that of a double dose (100 mg) of conventional immediate-release metoprolol tablets in 64 hypertensives in a randomized, double-blind, crossover study. At the end of a 6-week placebo run-in period and after each of two 8-week active treatment periods, 3-min bicycle exercise tests were performed at 25, 1.3, and 5 h after dose intake. Twenty-five hours after dose the mean supine SBP/DBP on metoprolol CR 50 mg was 147/95 mm Hg and on conventional metoprolol 100 mg 148/94 mm Hg, respectively. The percentage of responders (DBP less-than-or-equal 90 mm Hg or reduction in DBP greater-than-or-equal 10 mm Hg) was 45% on both regimens. At 25 h after dose, exercise heart rate was lower on 50 mg metoprolol CR (136 versus 140 beats min(minus sign1); p < 0.001) than on 100 mg conventional metoprolol, whereas the opposite was found at 1.3 h (131 versus 107 beats min(minus sign1); p < 0.001) and at 5 h (131 versus 113 beats min(minus sign1); p < 0.001). In agreement with the more even plasma metoprolol concentration and exercise heart rate, the patients perceived less fatigue during exercise on 50 mg metoprolol CR at 1.3 h after dose, the approximate time of maximum plasma concentration for 100 mg conventional metoprolol. The total number of adverse events recorded on metoprolol CR 50 mg and conventional metoprolol 100 mg were 62 and 103, respectively (p < 0.01). Thus, this study has demonstrated that the new controlled-release formulation of metoprolol has made it possible to halve the dose of metoprolol and yet achieve the same blood pressure control as well as greater beta(1)-blockade at the end of 24-h dosing intervals. Corresponding to lower peak plasma metoprolol concentrations, perceived fatigue and overall tolerability was improved on metoprolol CR 50 mg compared to conventional metoprolol 100 mg.