title: Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring.
abstract: Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double-blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24-hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP (-14.9 mm Hg and -15.3 mm Hg, respectively) more than VAL 320 mg (-11.3 mm Hg; P<.001 for 40-mg and 80-mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results (-14.9 mm Hg for AZL-M 40 mg and -16.9 mm Hg for AZL-M 80 mg vs -11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL (P≤.001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL-M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class.
authors.affiliation: Section of Clinical Pharmacology and Hypertension, Virginia Commonwealth University, Richmond, VA 23298-0160, USA. dsica@mcvh-vcu.edu
authors.forename: Domenic
authors.initials: D
authors.lastname: Sica
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: Alfonso
authors.initials: A
authors.lastname: Perez
authors.forename: Charlie
authors.initials: C
authors.lastname: Cao
authors.forename: Alison
authors.initials: A
authors.lastname: Handley
authors.forename: Stuart
authors.initials: S
authors.lastname: Kupfer
mesh_terms: D000367:Age Factors; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012737:Sex Factors; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D010069:Oxadiazoles; D013777:Tetrazoles; D000068756:Valsartan; C521273:azilsartan; D014633:Valine