Abstract |
Azilsartan medoxomil, an effective, long-acting angiotensin II receptor blocker, is a new treatment for hypertension that is also being developed in fixed-dose combinations with chlorthalidone, a potent, long-acting thiazide-like diuretic. We compared once-daily fixed-dose combinations of azilsartan medoxomil/ chlorthalidone force titrated to a high dose of either 40/25 mg or 80/25 mg with a fixed-dose combination of the angiotensin II receptor blocker olmesartan medoxomil plus the thiazide diuretic hydrochlorothiazide force titrated to 40/25 mg. The design was a randomized, 3-arm, double-blind, 12-week study of 1071 participants with baseline clinic systolic blood pressure 160 to 190 mm Hg and diastolic blood pressure ≤119 mm Hg. Patients had a mean age of 57 years; 59% were men, 73% were white, and 22% were black. At baseline, mean clinic blood pressure was 165/96 mm Hg and 24-hour mean blood pressure was 150/88 mm Hg. Changes in clinic (primary end point) and ambulatory systolic blood pressures at week 12 were significantly greater in both azilsartan medoxomil/ chlorthalidone arms than in the olmesartan/ hydrochlorothiazide arm (P<0.001). Changes in clinic systolic blood pressure (mean±SE) were -42.5±0.8, -44.0±0.8, and -37.1±0.8 mm Hg, respectively. Changes in 24-hour ambulatory systolic blood pressure were -33.9±0.8, -36.3±0.8, and -27.5±0.8 mm Hg, respectively. Adverse events leading to permanent drug discontinuation occurred in 7.9%, 14.5%, and 7.1% of the groups given azilsartan medoxomil/ chlorthalidone 40/25 mg, azilsartan medoxomil/ chlorthalidone 80/25 mg, and olmesartan/ hydrochlorothiazide 40/25 mg, respectively. This large, forced-titration study has demonstrated superior antihypertensive efficacy of azilsartan medoxomil/ chlorthalidone fixed-dose combinations compared with the maximum approved dose of olmesartan/ hydrochlorothiazide.
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Authors | William C Cushman, George L Bakris, William B White, Michael A Weber, Domenic Sica, Andrew Roberts, Eric Lloyd, Stuart Kupfer |
Journal | Hypertension (Dallas, Tex. : 1979)
(Hypertension)
Vol. 60
Issue 2
Pg. 310-8
(Aug 2012)
ISSN: 1524-4563 [Electronic] United States |
PMID | 22710649
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Benzimidazoles
- Diuretics
- Imidazoles
- Oxadiazoles
- Tetrazoles
- Hydrochlorothiazide
- olmesartan
- azilsartan medoxomil
- Chlorthalidone
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Topics |
- Aged
- Angiotensin II Type 1 Receptor Blockers
(pharmacology, therapeutic use)
- Benzimidazoles
(pharmacology, therapeutic use)
- Black People
- Blood Pressure
(drug effects, physiology)
- Chlorthalidone
(pharmacology, therapeutic use)
- Diuretics
(pharmacology, therapeutic use)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Humans
- Hydrochlorothiazide
(pharmacology, therapeutic use)
- Hypertension
(classification, drug therapy, ethnology)
- Imidazoles
(pharmacology, therapeutic use)
- Male
- Middle Aged
- Oxadiazoles
(pharmacology, therapeutic use)
- Severity of Illness Index
- Tetrazoles
(pharmacology, therapeutic use)
- Treatment Outcome
- White People
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