FIRST-LINE THERAPY OPTION WITH LOW-DOSE BISOPROLOL FUMARATE AND LOW-DOSE HYDROCHLOROTHIAZIDE IN PATIENTS WITH STAGE-I AND STAGE-II SYSTEMICHYPERTENSION

This 30-center, randomized, double-blind, placebo-controlled, parallel -group study was designed to (1) establish that 6.25 mg of hydrochloro thiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemic hypertension; and (2) assess whether this formulation was more effective or possessed a safety adva ntage over standard monotherapy with bisoprolol or 25 mg of HCTZ. Resu lts showed that HCTZ 6.25 mg contributed significantly to the antihype rtensive effectiveness of bisoprolol 5 mg. Bisoprolol 5 mg/HCTZ 6.25 m g (B5/H6.25) produced significantly greater mean reductions from basel ine in sitting systolic and diastolic blood pressure (-15.8 mm Hg/-12. 6 mm Hg) than bisoprolol 5 mg alone (-10.0 mm Hg/-10.5 mm Hg) and HCTZ 25 mg alone (-10.2 mm Hg/-8.5 mm Hg). A 73% response rate was achieve d with the low-dose formulation compared with 61% for the bisoprolol 5 mg (B5) group and 47% for the HCTZ 25 mg (H25) group. B5/H6.25 was fo und to be significantly more effective than B5 or H25 in all subgroups of patients, regardless of gender, race, age, or smoking history. Ant ihypertensive effects were maintained during the 24-hour dosing interv al. The incremental effectiveness of B5/H6.25 was not accompanied by a n in crease in the frequency or severity of adverse experiences; the i ncidence of adverse experiences in the B5/H6.25 group was comparable t o that in the placebo group. B5/H6.25 was shown to provide safety adva ntages over H25, as shown by less hypokalemia (<1% with B5/H6.25 versu s 6.5% with H25). Treatment effects on triglycerides were similar to p lacebo, although small decreases in high-density lipoprotein (HDL) cho lesterol were observed in the bisoprolol-treated groups. The benefits of low-dose bisoprolol 5 mg/HCTZ 6.25 mg provide a rational basis for the use of this medication in the first-line treatment of patients wit h stage I and stage II systemic hypertension.