Blood Pressure-Lowering Efficacy of the Fixed-Dose Combination of Azilsartan Medoxomil and Chlorthalidone: A Factorial Study

摘要

This study compared the efficacy and safety of fixed-dose combinations (FDCs) of the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the thiazide-like diuretic chlorthalidone (CLD) with the individual monotherapies in a double-blind factorial study. A total of 1714 patients with clinic systolic blood pressure (SBP) 160mmHg to 190mmHg inclusive were randomized to AZL-M 0mg, 20mg, 40mg, or 80mg and/or chlorthalidone 0mg, 12.5mg, or 25mg. The primary efficacy end point was change from baseline to 8weeks in trough (hour 22-24) SBP by ambulatory blood pressure (BP) monitoring (ABPM). Patients' mean age was 57years; 47% were men and 20% were black. Baseline trough BP was approximately 165/95mmHg and 151/91mmHg by clinic and ABPM measurements, respectively. For the pooled AZL-M/CLD 40/25-mg and 80/25-mg FDC groups, SBP reduction by ABPM at trough was 28.9mmHg and exceeded AZL-M 80mg and CLD 25mg monotherapies by 13.8mmHg and 13mmHg, respectively (P<.001 for both comparisons). Discontinuation rates and elevations in serum creatinine were dose-dependent and occurred more often in the AZL-M/CLD groups. In patients with stage 2 hypertension, treatment with the combination of AZL-M and CLD resulted in substantially greater SBP reduction compared with either agent alone.