LOSARTAN AND LOW-DOSE HYDROCHLOROTHIAZIDE IN PATIENTS WITH ESSENTIAL-HYPERTENSION - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF CONCOMITANTADMINISTRATION COMPARED WITH INDIVIDUAL COMPONENTS

Background: Angiotensin II acts at the cellular level through specific angiotensin II subtype I, AT-1 receptors. Losartan is the first of a new class of antihypertensive agents that specifically block angiotens in II at AT-1 receptors, By acting on complementary and different phar macologic mechanisms, the concomitant use of low doses of hydrochlorot hiazide with losartan may offer an additive antihypertensive activity with fewer adverse experiences. Methods: This double-blind study evalu ated losartan concomitantly administered with hydrochlorothiazide as i nitial therapy in 703 patients with essential hypertension. Results: T he greatest reduction in blood pressure was observed in the 50 mg of l osartan potassium and 12.5 mg of hydrochlorothiazide group (17.2 mm Hg in sitting systolic blood pressure and 13.2 mm Hg in sitting diastoli c blood pressure [P less than or equal to.001]), and the effects of th e two components appeared to be additive. Seventy-eight percent of the patients treated with 50 mg of losartan potassium and 12.5 mg of hydr ochlorothiazide had an excellent or good antihypertensive response (si tting diastolic blood pressure <90 mm Hg or greater than or equal to 9 0 mm Pig with a reduction of 10 mm I-Ig or more). Peak (6 hours after dosing) and trough placebo-adjusted ratios for the losartan-hydrochlor othiazide groups ranged from 62% to 85%, indicating that there was a s mooth reduction in sitting diastolic blood pressure that was sustained over 24 hours. The most common clinical adverse experiences (greater than or equal to 4%) that occurred with an incidence slightly greater than that reported by the placebo-treated patients were headache, asth enia or fatigue, dizziness, sinusitis, and upper respiratory infection . Conclusion: The concomitant administration of losartan potassium, 50 mg, with 12.5 mg of hydrochlorothiazide once daily produced an additi ve reduction in trough sitting systolic and diastolic blood pressure a nd was well tolerated.