Efficacy and safety of azilsartan medoxomil/chlortalidone fixed-dose combination in hypertensive patients uncontrolled on azilsartan medoxomil alone: A randomized trial

Patients with grade 2-3 essential hypertension and postplacebo mean clinic systolic blood pressure (SBP) 160-190 mm Hg and 24-hour SBP 140-175 mm Hg by ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil (AZL-M) monotherapy for 4 weeks. "Nonresponders" were then randomized to 8 weeks of double-blind treatment with AZL-M 40 mg, AZL-M/chlortalidone (CLD) 40/25, or AZL-M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was-21.1 (+/- 1.04) mm Hg for AZL-M/CLD 40/25 mg, -15.8 (+/- 1.08) mm Hg for AZL-M/CLD 40/12.5 mg, and -6.4 (+/- 1.05) mm Hg for AZL-M 40 mg (P < 0.001 for both AZL-M/CLD vs AZL-M, ANCOVA). Drug discontinuation rates were 8.9% (AZL-M/CLD 40/25 mg), 7.5% (AZL-M 40 mg), and 3.9% (AZL-M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL-M/CLD 40/25), 3.1% (AZL-M/CLD 40/12.5 mg), and 3.0% (AZL-M 40 mg) of patients. AZL-M/CLD was effective and well tolerated in patients not achieving blood pressure targets with AZL-M.