BACKGROUND:Losartan potassium is a recently marketed angiotensin II receptor antagonist. Previous studies have suggested that its full antihypertensive efficacy may be delayed for up to 12 weeks. The authors compared the antihypertensive efficacy and tolerability of losartan at 6 and 12 weeks with those of amlodipine besylate, a commonly used calcium antagonist. METHODS: This multicentre, randomized, double-blind clinical trial studied 302 patients with mild or moderate hypertension in 1995. Of the 302, 97 also underwent ambulatory blood pressure monitoring (ABPM). After a 4-week placebo run-in period, the patients were randomly assigned to group A, B or C for 12 weeks. Those in groups A and B began treatment with losartan at 50mg/d, and those in group C began with amlodipine at 5 mg/d. If the blood pressure remained uncontrolled 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 patients in group C had their amlodipine dose doubled (to 10 mg/d). RESULTS: At 12 weeks all 3 regimens reduced office-recorded diastolic blood pressure (DBP) with the patient sitting. The mean reduction in group A was 8.7 mm Hg (95% confidence interval [CI] 7.3 to 10.1) (p < 0.001), in group B 12.5 mm Hg (95% CI 11.0 to 14.0) (p < 0.001) and in group C 12.9 mm Hg (95% CI 11.4 to 14.5) (p < 0.001). Losartan alone lowered sitting DBP to a lesser degree than the other 2 treatments (p < 0.01). In contrast, ABPM readings, whether 24-hour, daytime or nighttime, were not different among the regimens. Comparison of the results at 6 weeks yielded similar findings. Adverse effects were uncommon and were not 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 or the combination of losartan and hydrochlorothiazide, but ABPM did not confirm this difference. Perhaps changes in office readings measure different attributes of a drug than does ABPM.
RCT Entities:
BACKGROUND:Losartan potassium is a recently marketed angiotensin II receptor antagonist. Previous studies have suggested that its full antihypertensive efficacy may be delayed for up to 12 weeks. The authors compared the antihypertensive efficacy and tolerability of losartan at 6 and 12 weeks with those of amlodipine besylate, a commonly used calcium antagonist. METHODS: This multicentre, randomized, double-blind clinical trial studied 302 patients with mild or moderate hypertension in 1995. Of the 302, 97 also underwent ambulatory blood pressure monitoring (ABPM). After a 4-week placebo run-in period, the patients were randomly assigned to group A, B or C for 12 weeks. Those in groups A and B began treatment with losartan at 50mg/d, and those in group C began with amlodipine at 5 mg/d. If the blood pressure remained uncontrolled 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 patients in group C had their amlodipine dose doubled (to 10 mg/d). RESULTS: At 12 weeks all 3 regimens reduced office-recorded diastolic blood pressure (DBP) with the patient sitting. The mean reduction in group A was 8.7 mm Hg (95% confidence interval [CI] 7.3 to 10.1) (p < 0.001), in group B 12.5 mm Hg (95% CI 11.0 to 14.0) (p < 0.001) and in group C 12.9 mm Hg (95% CI 11.4 to 14.5) (p < 0.001). Losartan alone lowered sitting DBP to a lesser degree than the other 2 treatments (p < 0.01). In contrast, ABPM readings, whether 24-hour, daytime or nighttime, were not different among the regimens. Comparison of the results at 6 weeks yielded similar findings. Adverse effects were uncommon and were not 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 or the combination of losartan and hydrochlorothiazide, but ABPM did not confirm this difference. Perhaps changes in office readings measure different attributes of a drug than does ABPM.
Authors: B Pitt; R Segal; F A Martinez; G Meurers; A J Cowley; I Thomas; P C Deedwania; D E Ney; D B Snavely; P I Chang Journal: Lancet Date: 1997-03-15 Impact factor: 79.321
Authors: J D Neaton; R H Grimm; R J Prineas; J Stamler; G A Grandits; P J Elmer; J A Cutler; J M Flack; J A Schoenberger; R McDonald Journal: JAMA Date: 1993-08-11 Impact factor: 56.272
Authors: Alan R Katritzky; C Dennis Hall; Bahaa El-Dien M El-Gendy; Bogdan Draghici Journal: J Comput Aided Mol Des Date: 2010-05-20 Impact factor: 3.686
Authors: Robert A Phillips; Robert A Kloner; Richard H Grimm; Myron Weinberger Journal: J Clin Hypertens (Greenwich) Date: 2003 Jan-Feb Impact factor: 3.738