Dose-related efficacy of irbesartan for hypertension: an integrated analysis.
Results of eight multicenter, randomized, placebo-controlled, double-blind, parallel-group studies were pooled to assess the efficacy of the angiotensin II-receptor blocker irbesartan over the dose range of 1 to 900 mg. A total of 2955 adults with a seated diastolic blood pressure of 95 to 110 mm Hg were randomized to treatment with oral irbesartan once daily or placebo for 6 to 8 weeks. Office blood pressure was measured at trough (24+/-3 hours after the last dose) and peak (3+/-1 hours after the last dose) by mercury sphygmomanometry. Demographic characteristics (mean blood pressure; 151/101 mm Hg; mean age, 54 years; 63% male; and 82% white) were similar across all dose groups. After the groups were pooled, antihypertensive efficacy was assessed by therapeutic response (trough seated diastolic blood pressure <90 mm Hg or a reduction from baseline of > or = 10 mm Hg) and by modeling of the maximum reductions in trough and peak seated diastolic and systolic blood pressure. Antihypertensive effects increased with increasing doses and reached a plateau at > or = 300 mg. Irbesartan 150 mg provided placebo-subtracted reductions in trough seated systolic and diastolic blood pressure of approximately 8 and approximately 5 mm Hg, respectively, with 56% of patients displaying a favorable response. In conclusion, irbesartan provides clinically significant blood pressure lowering, with a clear relationship between (log) dose and antihypertensive effect.
Reeves
R A
RA
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. richard_a._reeves@ccmail.bms.com
Lin
C S
CS
Kassler-Taub
K
K
Pouleur
H
H
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D010919:Placebos; D013777:Tetrazoles / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D010919:Placebos; D013777:Tetrazoles; D000077405:Irbesartan