Timolol and hydrochlorothiazide-amiloride in primary hypertension

Fifty-five patients with primary hypertension, World Health Organization (WHO) stages I and II, were randomly allocated to a 9-mo multicenter, controlled, double-blind, crossover study with timolol, a nonselective beta adrenoceptor blocker, and hydrochlorothiazide combined with the potassium-sparing drug amiloride (AHCT). In 54% of the patients the blood pressure responded to timolol, in 87% to AHCT, and in 91% to a combination of the two. The diurectic was more effective than the beta blocker in patients with low-renin hypertension, who all responded to AHCT. Overall, there was no correlation between pretreatment plasma renin activity (PRA) and hypothensive effect of either drug. Timolol reduced PRA by 58% and plasma aldosterone (PA) by 23% while AHCT increased these levels threefold. Combination therapy increased PA while PRA returned towards baseline, suggesting greater aldosterone stimulation by the diuretic component. Serum triglycerides rose during timolol treatment alone and in combination. Both timolol and AHCT are effective antihypertensives. In combination they normalize blood pressure in most patients with primary hypertension (WHO stages I and II). Determination of PRA is useful as a guide to the choice of the first treatment in searching out low-renin hypertensive patients, who are best treated with diuretics.