Propranolol-hydrochlorothiazide combination in essential hypertension

The effect of a propranolol-hydrochlorothiazide combination tablet was compared with the effects of its two components alone in the twice-daily treatment of mild to moderate essential hypertension (100 to 125 mmHg diastolic blood pressure). Propranolol alone or in combination was given at 80, 160, 240, or 320 mg/day; hydrochlorothiazide, at 50 mg/day. After a 3-week placebo period, a 12-week single-blind dose-finding test with the combination was held: 149/158 (94%) patients had decreases greater than or equal to 10 mmHg in diastolic blood pressure. Mean systolic and diastolic pressures were reduced by 26.6 mmHg 917%) and 19.2 mmHg (18.6%), respectively (P less than 0.001). A 10-week double-blind parallel treatment test followed, in which patients were assigned by random code to combination tablet, propranolol, or hydrochlorothiazide. There were significantly larger increases (P less than 0.05) in mean systolic or diastolic pressure with each component than with the combination from the end of dose-finding to each of the last four biweekly visits, to the mean of those four visits, and to the endpoint (last visit). The mean increases in pressure at the endpoint evaluation were (systolic/diastolic): combination (n = 47), 3.0/1.5 mmHg; propranolol (n = 51), 10.2/6.3 mmHg; hydrochlorothiazide (n = 52), 13.1/9.3 mmHg. During the double-blind period, no significant differences were demonstrated between the proportions of patients in each treatment group reporting new complaints. This study showed the combination to be as safe as, and more effective than, either component given at the same dose strength.