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 clin ical antihypertensive effects. The aim of the present study was to cha racterize the efficacy and duration of action of losartan by ambulator y blood pressure monitoring. Methods: The study was performed in nonbl ack hypertensive patients whose baseline untreated clinical diastolic blood pressures were 95 mm Hg or higher and whose average 24-hour ambu latory diastolic blood pressures were 85 mm Hg or higher. Patients wer e 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 pressure s were measured at baseline (off treatment for at least 4 weeks) and a fter 4 weeks of treatment. Results: By clinical sphygmomanometer measu rements at the end of the 24-hour or 12-hour dosing intervals (trough) , all three losartan dosages were significantly more effective than pl acebo at decreasing systolic and diastolic blood pressures. By average 24-hour ambulatory systolic/ diastolic blood pressure measurements, t he 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 diffe rent 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 losart an, 50 mg once daily (P<.05). Addition of hydrochlorothiazide, 12.5 mg /d, during an additional 2-week treatment period in patients whose cli nical diastolic blood pressure remained at 85 mm Hg or higher while re ceiving monotherapy produced additional and clinically meaningful. blo od pressure decrements that were similar in all four treatment groups. There were no clinical adverse events in any group. Conclusion: Ambul atory blood pressure monitoring, which virtually eliminated antihypert ensive placebo responses, demonstrated clear 24-hour efficacy for losa rtan, 50 mg once daily, as well as for higher doses of 100 mg once dai ly and 50 mg twice daily. This ATI receptor blocker had antihypertensi ve effects that appeared additive when combined with low-dose diuretic therapy. Losartan was generally well tolerated.