THE ANTIHYPERTENSIVE EFFICACY OF LOSARTAN AND AMLODIPINE ASSESSED WITH OFFICE AND AMBULATORY BLOOD-PRESSURE MONITORING

Background: Losartan potassium is a recently marketed angiotensin II r eceptor antagonist. Previous studies have suggested that its full anti hypertensive effect may be delayed for up to 12 weeks. The authors com pared the antihypertensive efficacy and tolerability of losartan at 6 and 12 weeks with those of amlodipine besylate, a commonly used calciu m antagonist. Methods: This multicentre, randomized, double-blind clin ical trial studied 302 patients with mild or moderate hypertension in 1995. Of the 302, 97 also underwent ambulatory blood pressure monitori ng (ABPM). After a 4-week placebo run-in period, the patients were ran domly assigned to group A, B or C for 12 weeks. Those in groups A and B began treatment with losartan at 50 mg/d, and those in group C began with amlodipine at 5 mg/d. if the blood pressure remained uncontrolle d after 6 weeks, subjects in group A had their losartan dose doubled ( to 100 mg/d), those in group B were given hydrochlorothiazide (12.5 mg /d) in addition to the losartan, which remained at 50 mg/d, and patien ts in group C had their amlodipine dose doubled (to 10 mg/d). Results: At 12 weeks all 3 regimens reduced office-recorded diastolic blood pr essure (DBP) with the patient sitting. The mean reduction in group A w as 8.7 mm Hg (95% confidence interval [CI] 7.3 to 10.1) (p < 0.001), i n group B 12.5 mm Hg (95% Cl 11.0 to 14.0) (p < 0.001) and in group C 12.9 mm Hg (95% Cl 11.4 to 14.5) (p < 0.001). Losartan alone lowered s itting DBP to a lesser degree than the other 2 treatments (p < 0.01). in contrast, ABPM readings, whether 24-hour, daytime or nighttime, wer e not different among the regimens. Comparison of the results at 6 wee ks yielded similar findings. Adverse effects were uncommon and were no t different among the groups, with the exception of ankle edema, which was more frequent in group C. Interpretation: Losartan alone reduces both office and ABPM readings. The observed changes in office-recorded sitting DBP suggest that losartan is less effective than amlodipine o r the combination of losartan and hydrochlorothiazide, but ABPM did no t confirm this difference. Perhaps changes in office readings measure different attributes of a drug than does ABPM.