A Titrate-to-Goal Study of Switching Patients Uncontrolled on Antihypertensive Monotherapy to Fixed-Dose Combinations of Amlodipine and Olmesartan Medoxomil ± Hydrochlorothiazide

In the prospective, open-label, titrate-to-goal Blood Pressure Control in All Subgroups With Hypertension (BP-CRUSH) study, 999 patients with hypertension uncontrolled on monotherapy (mean age, 55.6±11.4years; baseline blood pressure [BP], 153.7±9.2/91.9±8.6mm Hg) were switched to fixed-dose amlodipine/olmesartan medoxomil (AML/OM) 5/20mg. Patients were uptitrated every 4weeks to AML/OM 5/40 mg and 10/40mg to achieve BP <120/70mm Hg. Patients were subsequently uptitrated every 4weeks to AML/OM+hydrochlorothiazide (HCTZ) 10/40+12.5 mg and 10/40+25mg to achieve BP <125/75mm Hg. The primary end point, the cumulative percentage of patients achieving seated systolic BP <140mm Hg (<130mm Hg for patients with diabetes) by week 12, was 75.8%. The mean (±standard error) BP changes from baseline during the titration periods ranged from -14.2±0.4 mm Hg/-7.7±0.3mm Hg for AML/OM 5/20mg to -25.1±0.7 mm Hg/-13.7±0.4mm Hg for AML/OM+HCTZ 10/40+25mg. By week 20, the cumulative BP threshold of <140/90mm Hg was achieved by 90.3% of patients. An ambulatory BP monitoring substudy (n=243) showed that 24-hour efficacy was maintained. Treatment-emergent adverse events (TEAEs), mostly mild to moderate in severity, occurred in 529 patients (53.0%). Drug-related TEAEs occurred in 255 patients (25.5%). This well-tolerated, treat-to-goal algorithm enabled a large proportion of patients with uncontrolled hypertension on monotherapy to safely achieve BP control on single-pill AML/OM combination therapy or triple therapy with the addition of HCTZ.