A titrate-to-goal study of switching patients uncontrolled on antihypertensive monotherapy to fixed-dose combinations of amlodipine and olmesartan medoxomil ± hydrochlorothiazide

Abstract

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 ± 11.4 years; baseline blood pressure [BP], 153.7 ± 9.2/91.9 ± 8.6 mm Hg) were switched to fixed-dose amlodipine/olmesartan medoxomil (AML/OM) 5/20 mg. Patients were uptitrated every 4 weeks to AML/OM 5/40 mg and 10/40 mg to achieve BP < 120/70 mm Hg. Patients were subsequently uptitrated every 4 weeks to AML/OM+hydrochlorothiazide (HCTZ) 10/40+12.5 mg and 10/40+25 mg to achieve BP <125/75 mm Hg. The primary end point, the cumulative percentage of patients achieving seated systolic BP < 140 mm Hg (< 130 mm 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 ± 0.3 mm Hg for AML/OM 5/20 mg to -25.1 ± 0.7 mm Hg/-13.7 ± 0.4 mm Hg for AML/OM+HCTZ 10/40+25 mg. By week 20, the cumulative BP threshold of <140/90 mm 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. .

Figure 1

Proportions of patients achieving the seated cuff systolic blood pressure (SeSBP) goal (<140 mm Hg [<130 mm Hg for patients with diabetes]) by week 12. The cumulative blood pressure (BP) goal achievement rate at week 12 was calculated as the ratio of the number of patients who achieved the goal at any time from the first dose to week 12 over the number of patients who had any post‐baseline BP data. The noncumulative (last‐observation‐carried‐forward [LOCF]) BP goal achievement rate by visit was calculated as the ratio of the number of patients who achieved the goal at week 12 (when missing, at the last available visit, ie, LOCF) over the number of patients who had any post‐baseline BP data.

Figure 2

Change from baseline in seated cuff blood pressure (SeBP) (A) and proportions of patients achieving SeBP threshold of <140/90 mm Hg by titration dose (B). AML indicates amlodipine; HCTZ, hydrochlorothiazide; OM, olmesartan medoxomil; SeDBP, seated cuff diastolic blood pressure; SeSBP, seated cuff systolic blood pressure. The cumulative blood pressure (BP) goal achievement rate at each titration period was calculated as the ratio of the number of patients who achieved the goal at any time from the first dose to the end of the titration dose period over the number of patients who had any post‐baseline BP data during the titration dose period. The noncumulative (last‐observation‐carried‐forward [LOCF]) BP goal achievement rate by visit was calculated as the ratio of the number of patients who achieved the goal at the end of the titration dose period (when missing, at the last available visit, ie, LOCF) over the number of patients who had any post‐baseline BP data during the titration dose period.

Figure 3

Change in mean ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) (±standard error of the mean) during the 24‐hour dosing interval and daytime, nighttime, and last 2, 4, and 6 hours of the dosing interval at week 12 (A) and week 20 (B).

Figure 4

Ambulatory systolic blood pressure (SBP) over the 24‐hour dosing interval at week 12 (A) and week 20 (B). Time 0 represents 12 am. Dosing occurred at 8 am±120 minutes.

Figure 5

Proportion of patients achieving mean 24‐hour, daytime (8 am–4 pm), and nighttime (10 pm–6 am) ambulatory blood pressure targets at weeks 12 and 20. ABPM indicates ambulatory blood pressure monitoring.