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 a ction and additive effects may achieve control of blood pressure and m inimize the dose-dependent adverse effects seen with conventional mono therapy, a randomized, double-blind parallel group dose-escalation stu dy 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) wit h 6.25 mg of hydrochlorothiazide (HCTZ). All drugs were administered o nce daily, titrated to optimal response, and taken for a total of 12 w eeks. Blood pressure was measured 24 hours after dose. The response ra tes (either a diastolic blood pressure less than or equal to 90 mm Hg or a decrease of diastolic pressure greater than or equal to 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 fr om baseline were 13.4/10.7, 12.8/10.2, and 7.3/6.6 mm Hg for bisoprolo l-6.25 mg HCTZ, amlodipine, and enalapril, respectively. The mean chan ge with enalapril was less than the other drugs (p < 0.01), although t he once-daily dosing of enalapril and the maximum dose of 20 mg might not have been optimal for this agent. Overall adverse events for bisop rolol-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 adve rse events were 16%, 21%, and 23% (no significant difference), respect ively. Changes in quality of life scores as measured by the General We ll-Being Index were +0.9 for bisoprolol-6.25 mg HCTZ, +0.5 for amlodip ine, and -2.3 for enalapril, with a positive change indicating improve ment. This study demonstrates that low-dose combination therapy with b isoprolol-6.25 mg HCTZ is effective and well tolerated. Thus low-dose combination therapy appears to be a rational alternative for initiatin g therapy of mild to moderate hypertension.