Vol. 5, Issue 2 (2019)
Evaluation of efficacy and safety of fixed- dose combinations of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide
Author(s): Dr. Sanjay Kumar Jangid, Sudeep Kumar Patra, Saiprasanna Behera
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 71 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. 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 forced-titration study has demonstrated superior antihypertensive efficacy of azilsartan medoxomil/chlorthalidone fixed-dose combinations compared with the maximum approved dose of olmesartan/hydrochlorothiazide.