Twenty-nine patients with mild to severe essential hypertension were treated with titrated doses of xipamide, before or after treatment with 50 and , if necessary, 100 mg hydrochlorothiazide in a 13- to 25-week open crossover study. Based on supine diastolic pressure readings taken at weekly intervals, xipamide controlled hypertension in all subjects: 17 achieved control with a daily dose of 5 mg; seven, with 10 mg; and five, with 20 mg. In contrast, eight of the 29 patients could not be controlled with 100 mg/day hydrochlorothiazide. The only significant biochemical change observed was an increase in serum uric acid in 12 patients after hydrochlorothiazide but in only six patients after xipamide. Natriuresis was comparable after both drugs; 5 and 10 mg xipamide were as effective as 50 and 100 mg hydrochlorothiazide. The only side effect noted, cramping due to hypokalemia, occurred during treatment with hydrochlorothiazide, but not xipamide, and was reversed by potassium supplements.

The beta-adrenergic blocker sotalol, administered only once a day, proved an extremely effective and safe agent for the 24-hour control of essential hypertension, even in patients with a severe form of the disease. Significant (P less than 0.01) decreases from the baseline levels were noted in both supine and standing blood pressures as early as the first week after sotalol administration in the 15 patients who participated in the open study. All patients were titrated and controlled by six to eight weeks or sooner. By the conclusion of the 12-week study, mean supine systolic blood pressure in the 15 patients fell 21 per cent (from 176 mm Hg to 139 mm Hg), and mean supine diastolic blood pressure was down 23 per cent (from 115 mm Hg to 89 mm Hg). Standing values were similarly decreased by sotalol administration at a mean daily dose of 341 mg. Two of the patients also received concomitant 25 mg hydrochlorothiazide per day, and four received 40 mg furosemide per day. A comparison with the pretherapy placebo values indicates that all the declines were highly significant (P less than 0.001). Sotalol was very well tolerated, an no adverse reactions were reported during the entire study. There were also no significant changes in laboratory findings except for a drop in serum cholesterol.