Antihypertensive effect and tolerability of two fixed combination of metoprolol and hydrochlorothiazide followed by a long-term tolerance study with one combination.

After a run-in period with metoprolol 100 mg b.i.d. 55 patients with essential hypertension grade WHO I and II were randomly allocated to a fixed combination of metoprolol 100 mg and hydrochlorothiazide 12.5 mg (group A) or 25 mg (group B) b.i.d for 12 weeks. Every fourth week blood pressure, heart rate and side effects were registered. After 12 weeks there was a significant fall in supine blood pressure from 172/105 mm Hg to 148/92 in group A and from 170/104 mm Hg to 152/96 in group B. Serum potassium fell significantly (from 4.4 to 4.0 mmol/l) in group B only. 4 patients had values between 3.5 and 3.2 mmol/l. Serum uric acid was unchanged in both groups. Side effects were few and mild to moderate in both groups but there was a tendency to more side effects in group B. After 6 months' follow-up, 51 patients on treatment with low dose combination showed no further change in blood pressure. 27 patients took part in an extended follow-up study to 15 months and 13 patients to 18 months. During the whole follow-up study there was no further change in blood pressure, laboratory values or side effects. The study has confirmed that a low dose of hydrochlorothiazide is as effective as a high dose when combined with metoprolol. Because of few side effects and good tolerability during long treatment we find that the low dose combination can be recommended in treatment of milk to moderate essential hypertension.