Antihypertensive Efficacy of Angiotensin Receptor Blockers in Combination With Hydrochlorothiazide: A Review of the Factorial‐Design Studies

Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends starting treatment with a thiazide diuretic or, when BP is >20/10 mm Hg above goal or in patients with diabetes, using two different antihypertensive agents. Searches of MEDLINE, EMBASE, and BIOSIS databases identified four similarly designed, randomized, factorial studies comparing various doses of angiotensin II receptor blockers with hydrochlorothiazide as monotherapy and in combination. The methodology and results of these studies were compared. The primary efficacy end point in these studies was a decrease from baseline in mean diastolic BP after 8 weeks of therapy. All currently available angiotensin I receptor blocker/hydrochlorothiazide combinations evaluated (irbesartan, olmesartan medoxomil, telmisartan, and valsartan plus hydrochlorothiazide) produced significant systolic BP and diastolic BP reductions. Olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg provided the largest mean reduction in absolute and placebo‐corrected systolic BP/diastolic BP. For all angiotensin II receptor blocker/hydrochlorothiazide combinations evaluated, ≥63% of patients achieved a diastolic BP response (diastolic BP <90 mm Hg or ≥10‐mm Hg reduction). In conclusion, the combination of an angiotensin II receptor blocker and hydrochlorothiazide produces more substantial BP responses than monotherapy with either component.