Efficacy and Safety of Triple Antihypertensive Therapy with the Olmesartan/Amlodipine/Hydrochlorothiazide Combination
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Background: European hypertension guidelines estimate that up to 15–20% of hypertensive patients are not controlled on a dual antihypertensive combination and require three or more different antihypertensive drug classes to achieve blood pressure (BP) control.
Objective: This study in patients with moderate-to-severe hypertension assessed the efficacy and safety of adding hydrochlorothiazide (HCTZ) 12.5 mg and 25 mg to a range of olmesartan medoxomil (OLM)/amlodipine (AML) doses. Study Design: This phase III, multicentre study had a randomized, double-blind, parallel-group design that included a double-blind safety run-in and a double-blind treatment period.
Intervention: Enrolled patients were screened and previous therapy was discontinued if required. During a 2-week, double-blind, safety run-in period (Weeks 0–2), patients were randomized to receive placebo, OLM/AML 20 mg/5 mg, OLM/AML 40 mg/5 mg or OLM/AML 40 mg/10 mg. During an 8-week, double-blind treatment period (Weeks 3–10), patients were allocated to eight groups depending on their initial treatment. They were either randomized to continue with the same dose of OLM/AML, or have HCTZ 12.5 mg or 25 mg added to treatment.
Main Outcome Measure: The primary endpoint was formulated before data collection began. It was the change in mean diastolic BP (DBP) from baseline to Week 10 in groups with HCTZ added to OLM/AML, compared with the corresponding dual OLM/AML therapy.
Results: Of 3195 patients who were screened, 2690 were randomized. Patients in every triple OLM/AML/HCTZ group had significantly greater mean reductions in DBP (p ≤ 0.032 for each comparison) and systolic BP (SBP) by Week 10 (p ≤ 0.0034 for each comparison), compared with patients on the corresponding OLM/AML therapy dose. The significant improvements in DBP and SBP reduction with triple OLM/AML/HCTZ therapy, compared with dual OLM/AML therapy, were observed after 4 and 6 weeks of therapy. Patients in each triple therapy group also had a significantly higher rate of BP < 140/90 mmHg threshold achievement (p ≤ 0.05 for each treatment comparison), compared with the dual OLM/AML groups. In three of the OLM/AML/HCTZ groups (40 mg/5 mg/25 mg, 40 mg/10 mg/12.5 mg and 40 mg/10 mg/25 mg), BP <140/90 mmHg threshold achievement by Week 10 was over 70%. Across the triple and dual combination therapy groups, treatment was well tolerated and no safety concerns for either treatment were identified.
Conclusion: Adding HCTZ to a range of OLM/AML dose combinations is well tolerated and improved BP control by significantly lowering DBP and SBP and significantly increasing BP threshold achievement in patients with moderate-to-severe hypertension.
Clinical Trial Registration: Registered at ClinicalTrials.gov identifier as NCT00923091.
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- Efficacy and Safety of Triple Antihypertensive Therapy with the Olmesartan/Amlodipine/Hydrochlorothiazide Combination
Clinical Drug Investigation
Volume 32, Issue 10 , pp 649-664
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- 1. Division of Cardiology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, University of Rome “La Sapienza”, Via di Grottarossa 1035-1039, Rome, I-00189, Italy
- 2. IRCCS Neuromed, Pozzilli, Italy
- 3. Department of Internal Medicine/Nephrology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- 4. Daiichi Sankyo Europe GmbH, Munich, Germany