Low-dose drug combination therapy: An alternative first-line approach to hypertension treatment

To investigate the concept that the initial treatment of hypertension with low doses of two antihypertensives that have different modes of action and additive effects may achieve control of blood pressure and minimize the dose-dependent adverse effects seen with conventional monotherapy, a randomized, double-blind parallel group dose-escalation study was conducted. After a 4 to 5 week placebo washout period, 218 men and women with diastolic blood pressure between 95 and 114 mm Hg were randomly allocated to take: amlodipine (2.5 to 10 mg), enalapril (5 to 20 mg), and the low-dose combination of bisoprolol (2.5 to 10 mg) with 6.25 mg of hydrochlorothiazide (HCTZ). All drugs were administered once daily, titrated to optimal response, and taken for a total of 12 weeks. Blood pressure was measured 24 hours after dose. The response rates (either a diastolic blood pressure ≤90 mm Hg or a decrease of diastolic pressure ≥10 mm Hg) were 71% for bisoprolol—6.25 mg HCTZ, 69% for amlodipine, and 45% for enalapril. The mean decreases in systolic/diastolic blood pressure from baseline were 13.4/10.7, 12.8/10.2, and 7.3/6.6 mm Hg for bisoprolol—6.25 mg HCTZ, amlodipine, and enalapril, respectively. The mean change with enalapril was less than the other drugs (p < 0.01), although the once-daily dosing of enalapril and the maximum dose of 20 mg might not have been optimal for this agent. Overall adverse events for bisoprolol—6.25 mg HCTZ, amlodipine, and enalapril were 29%, 42%, and 47% (p = 0.04, bisoprolol—6.25 mg HCTZ vs enalapril), and drug-related adverse events were 16%, 21%, and 23% (no significant difference), respectively. Changes in quality of life scores as measured by the General Well-Being Index were +0.9 for bisoprolol-6.25 mg HCTZ, +0.5 for amlodipine, and −2.3 for enalapril, with a positive change indicating improvement. This study demonstrates that low-dose combination therapy with bisoprolol—6.25 mg HCTZ is effective and well tolerated. Thus low-dose combination therapy appears to be a rational alternative for initiating therapy of mild to moderate hypertension.