title: Safety, tolerability, and efficacy of azilsartan medoxomil with or without chlorthalidone during and after 8 months of treatment for hypertension.
abstract: A phase 3, 26-week, open-label, titrate-to-target study (n=418) assessed the safety of azilsartan medoxomil (AZL-M) alone and with chlorthalidone (CLD), followed by a 6-week, double-blind, placebo-controlled reversal phase with change in clinic diastolic blood pressure (DBP) as the primary endpoint. Target blood pressure (BP) was <140/90 mm Hg (<130/80 mm Hg with diabetes/chronic kidney disease). AZL-M was initiated at 40 mg once a day (QD), force-titrated to 80 mg at week 4. CLD 25 mg QD could be added (weeks 8-22), if required, to reach target, followed by additional antihypertensives from week 12. At the end of the open-label phase, mean change in systolic BP (SBP)/DBP from baseline was -23/-16 mm Hg. The most common adverse events, irrespective of treatment, were dizziness (8.9%) and headache (7.2%). Serious AEs were reported in eight patients (1.9%). Consecutive creatinine elevations ≥50% with values exceeding the upper limit of normal (ULN) were reported in nine (2.2%) patients. All returned to below the 50% threshold; most also returned to below the ULN after drug discontinuation. Mean DBP was maintained through the reversal phase in patients receiving AZL-M, but increased with placebo (difference: -7.8 mm Hg, 95% confidence interval, -9.8 to -5.8; P<.001). AZL-M alone or with CLD showed good long-term safety and stable BP improvements in a titrate-to-target approach. BP improvements caused by AZL-M therapy were safely reversible upon AZL-M withdrawal.
authors.affiliation: Endocrinology Practice, San Antonio, TX.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kipnes
authors.forename: Alison
authors.initials: A
authors.lastname: Handley
authors.forename: Eric
authors.initials: E
authors.lastname: Lloyd
authors.forename: Bruce
authors.initials: B
authors.lastname: Barger
authors.forename: Andrew
authors.initials: A
authors.lastname: Roberts
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; 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; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D010069:Oxadiazoles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D004232:Diuretics; D010069:Oxadiazoles; C557413:azilsartan medoxomil; D002752:Chlorthalidone