Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension

William C. Cushman, George L. Bakris, William B. White, Michael A. Weber, Domenic Sica, Andrew Roberts, Eric Lloyd, Stuart Kupfer

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalHypertension
Volume60
Issue number2
DOIs
StatePublished - Aug 1 2012

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Chlorthalidone
Hydrochlorothiazide
Blood Pressure
Hypertension
Sodium Chloride Symporter Inhibitors
Angiotensin Receptor Antagonists
olmesartan
azilsartan medoxomil
Antihypertensive Agents

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. / Cushman, William C.; Bakris, George L.; White, William B.; Weber, Michael A.; Sica, Domenic; Roberts, Andrew; Lloyd, Eric; Kupfer, Stuart.

In: Hypertension, Vol. 60, No. 2, 01.08.2012, p. 310-318.

Research output: Contribution to journalArticle

Cushman, William C. ; Bakris, George L. ; White, William B. ; Weber, Michael A. ; Sica, Domenic ; Roberts, Andrew ; Lloyd, Eric ; Kupfer, Stuart. / Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. In: Hypertension. 2012 ; Vol. 60, No. 2. pp. 310-318.
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