title: Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study.
abstract: 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) 160 mm Hg to 190 mm Hg inclusive were randomized to AZL-M 0 mg, 20 mg, 40 mg, or 80 mg and/or chlorthalidone 0 mg, 12.5 mg, or 25 mg. The primary efficacy end point was change from baseline to 8 weeks in trough (hour 22-24) SBP by ambulatory blood pressure (BP) monitoring (ABPM). Patients' mean age was 57 years; 47% were men and 20% were black. Baseline trough BP was approximately 165/95 mm Hg and 151/91 mm Hg 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 28.9 mm Hg and exceeded AZL-M 80 mg and CLD 25 mg monotherapies by 13.8 mm Hg and 13 mm Hg, 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.
authors.affiliation: Division of Nephrology, Department of Medicine and Pharmacology, Virginia Commonwealth University, Richmond, VA, USA. dsica@mcvh-vcu.edu
authors.forename: Domenic
authors.initials: D
authors.lastname: Sica
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Patrick
authors.initials: P
authors.lastname: Huang
authors.forename: Andrew
authors.initials: A
authors.lastname: Roberts
authors.forename: Stuart
authors.initials: S
authors.lastname: Kupfer
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D044383:Black People / Q000208:ethnology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002752:Chlorthalidone / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D004232:Diuretics / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000208:ethnology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome; D044465:White People / Q000208:ethnology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D004232:Diuretics; D010069:Oxadiazoles; C557413:azilsartan medoxomil; D002752:Chlorthalidone