Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial

Abstract

Background: This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20 mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5).

Methods: In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ≥100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period.

Results: A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg (n = 32) or OM/AML/HCTZ 20/5/12.5 mg (n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were -9.50 (8.46) mmHg in the OM/AML/HCTZ group and -4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group (p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group (p = 0.0073 between groups). All medications were well tolerated.

Conclusion: In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850).

Fig. 1

Study flow and patient disposition. AML amlodipine, BP blood pressure, HCTZ hydrochlorothiazide, OM olmesartan medoxomil. Non-responders were defined as patients who did not meet BP goals [msSBP/msDBP <140/90 mmHg (msSBP/msDBP <130/80 mmHg in patients with diabetes or chronic kidney disease)]

Fig. 2

Changes in mean seated diastolic blood pressure (msDBP) (a) and mean seated systolic blood pressure (msSBP) (b) from randomization to weeks 4 and 8 of the double-blind treatment. AML amlodipine, HCTZ hydrochlorothiazide, OM olmesartan medoxomil. *p < 0.0001 vs. OM/HCTZ

Fig. 3

Changes in mean seated diastolic blood pressure (msDBP) (a) and mean seated systolic blood pressure (msSBP) (b) from week 8 to week 16 during the open-label period. AML amlodipine, HCTZ hydrochlorothiazide, OM olmesartan medoxomil. *p = 0.0434, ^† p = 0.1650, ^‡ p = 0.2012, ^§ p = 0.1085 vs. OM/AML/HCTZ 20/5/12.5, respectively

Fig. 4

Least-squares (LS) mean change in the mean seated diastolic blood pressure (msDBP) from randomization to 8 weeks of double-blind treatment according to sex, age, smoking status, and body mass index. *Adjusted for age, smoking, alcohol, and body mass index