BLOOD-PRESSURE EFFECTS OF THE ANGIOTENSIN-II RECEPTOR BLOCKER, LOSARTAN

Background: Losartan potassium, the first nonpeptide selective blocker of angiotensin II at the ATI receptor, has been shown to exhibit clinical antihypertensive effects. The aim of the present study was to characterize the efficacy and duration of action of losartan by ambulatory blood pressure monitoring. Methods: The study was performed in nonblack hypertensive patients whose baseline untreated clinical diastolic blood pressures were 95 mm Hg or higher and whose average 24-hour ambulatory diastolic blood pressures were 85 mm Hg or higher. Patients were randomized, double-blind, into four treatment groups: placebo (n=32) or losartan, 50 mg once daily (n=29), 100 mg once daily (n=30), or 50 mg twice daily (n=31). Clinical and 24-hour ambulatory blood pressures were measured at baseline (off treatment for at least 4 weeks) and after 4 weeks of treatment. Results: By clinical sphygmomanometer measurements at the end of the 24-hour or 12-hour dosing intervals (trough), all three losartan dosages were significantly more effective than placebo at decreasing systolic and diastolic blood pressures. By average 24-hour ambulatory systolic/ diastolic blood pressure measurements, the decreases produced were 0.0/0.2 mm Kg for placebo and 9.2/6.9, 9.9/6.4, and 13.2/8.5 mm Hg, respectively, for losartan, 50 mg once daily, 100 mg once daily, and 50 mg twice daily. All drug effects were different from placebo (P<.01). The effects of losartan, 50 mg twice daily, were not significantly different from those of losartan, 100 mg once daily, but, as expected, the effects were greater than those of losartan, 50 mg once daily (P<.05). Addition of hydrochlorothiazide, 12.5 mg/d, during an additional 2-week treatment period in patients whose clinical diastolic blood pressure remained at 85 mm Hg or higher while receiving monotherapy produced additional and clinically meaningful. blood pressure decrements that were similar in all four treatment groups. There were no clinical adverse events in any group. Conclusion: Ambulatory blood pressure monitoring, which virtually eliminated antihypertensive placebo responses, demonstrated clear 24-hour efficacy for losartan, 50 mg once daily, as well as for higher doses of 100 mg once daily and 50 mg twice daily. This ATI receptor blocker had antihypertensive effects that appeared additive when combined with low-dose diuretic therapy. Losartan was generally well tolerated.