Low-dose α/β blockade in the treatment of essential hypertension

Despite the recent emphasis on combination drug therapy for hypertension, little attention has been given to α/β blockade using agents other than labetalol. The purpose of this study was to 1) compare the efficacy of low-dose α/β blockade using doxazosin + betaxolol, versus monotherapy with an angiotensin converting enzyme inhibitor (quinapril) and a diuretic (hydrochlorothiazide [HCTZ]), and 2) assess the efficacy of low-dose doxazosin. In a crossover study, 21 hypertensive subjects were treated for 3 weeks each with HCTZ, 12.5 to 25 mg/day, quinapril, 10 to 40 mg/day, and a combination of doxazosin, 1 to 4 mg + betaxolol, 5 to 10 mg daily. Doses were titrated to achieve a systolic pressure <130 mm Hg, as assessed by self-recorded home measurements. Home blood pressure decreased 11.5/7.5 mm Hg after HCTZ, 12.9/8.8 mm Hg after quinapril, and 21.2/16.5 mm Hg after doxazosin + betaxolol (P< .001/< .001 v HCTZ and P< .002/< .001 v quinapril). The target systolic pressure was achieved by 33%, 43%, and 71% of subjects, respectively (P = .04 v HCTZ, and .03 v quinapril). Among the 8 subjects in whom doxazosin dosage was increased to the maximum of 4 mg, the mean blood pressure achieved at 4 mg did not differ from that achieved at 2 mg (136/87 v 136/88 mm Hg). We conclude that oral α/β blockade is superior to monotherapy with an angiotensin converting enzyme inhibitor or a diuretic and that maximal or near maximal efficacy can be achieved at a 2-mg dose of doxazosin. Low-dose oral α/β blockade merits greater consideration in the drug therapy of essential hypertension.