NEW YORK – The newly approved angiotensin II receptor blocker azilsartan combined in a fixed-dose with chlorthalidone lowered clinic systolic blood pressure significantly more than did the fixed-dose combination of olmesartan medoxomil plus hydrochlorothiazide in patients with type 2 hypertension.
At 12 weeks, both low-dose and high-dose azilsartan reduced in-clinic systolic blood pressure by an average of 42.5 mm Hg and 44.0 mm Hg, respectively. In comparison, the average reduction for patients on olmesartan was 37.1 mm Hg. The results were presented at the annual meeting of the American Society of Hypertension by Dr. William C. Cushman, chief of the preventive medicine section at the Veterans Affairs Medical Center in Memphis.
Dr. William C. Cushman
Azilsartan was approved by the Food and Drug Administration in February for the treatment of hypertension, alone or in combination with other antihypertensive treatment. The drug is being marketed as Edarbi by Takeda Pharmaceuticals North America.
In this phase III, double-blind trial, 1,071 patients with type 2 systolic hypertension were randomized to receive azilsartan 20 mg and the diuretic chlorthalidone 12.5 mg, azilsartan 40 mg and chlorthalidone 12.5 mg, or olmesartan (Benicar) 20 mg and hydrochlorothiazide 12.5 mg, following a 3-4 week washout with a 2-week placebo run-in.
At week 4, all patients underwent a forced titration, doubling the amount of azilsartan or olmesartan. At week 8, another forced titration doubled the amount of chlorthalidone or hydrochlorothiazide. At week 12, a final ambulatory blood pressure measurement was taken.
A total of 355 patients were in the low-dose azilsartan group, 352 were in the high-dose azilsartan group, and 364 were in the olmesartan group. Patients were at least 18 years old and had a systolic blood pressure between 160 and 190 mm Hg at a postwashout visit. Patients were excluded if they had secondary hypertension, had a sitting trough clinical diastolic blood pressure measurement more than 119 mm Hg, an estimated glomerular filtration rate less than 30 mL/min per 1.73 m2, a major cardiovascular event in the last 6 months, poorly controlled diabetes (hemoglobin A1c less than 8%), or hyper/hypokalemia.
The change in 24-hour mean systolic blood pressure was a reduction of 33.9 mm Hg and 36.3 mm Hg for the low and high doses of azilsartan, respectively, compared with a reduction of 27.5 mm Hg for the olmesartan group. The differences were significant. Likewise, the reduction in clinical diastolic blood pressure was also greater for those on azilsartan (18.8 mm Hg and 20.5 mm Hg) compared with those on olmesartan (16.4 mm Hg). These differences were also significant.
The percentage of patients reporting any adverse events was greater for those on azilsartan (71%) than for those on olmesartan (60%). However, the number of discontinuations due to adverse events was moderately greater in the high-dose azilsartan group.
The study was sponsored by the Takeda Global Research and Development Center. Three of the study authors are employees of Takeda. Dr. Cushman has reported significant financial relationships with several pharmaceutical companies, including Takeda Pharmaceuticals.