Abstract | 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: 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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Authors | Massimo Volpe, Lars Christian Rump, Bettina Ammentorp, Petra Laeis |
Journal | Clinical drug investigation
(Clin Drug Investig)
Vol. 32
Issue 10
Pg. 649-64
(Oct 01 2012)
ISSN: 1179-1918 [Electronic] New Zealand |
PMID | 22909147
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antihypertensive Agents
- Imidazoles
- Tetrazoles
- Hydrochlorothiazide
- Amlodipine
- olmesartan
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Topics |
- Adult
- Aged
- Aging
(physiology)
- Amlodipine
(administration & dosage, adverse effects, therapeutic use)
- Antihypertensive Agents
(administration & dosage, therapeutic use)
- Double-Blind Method
- Drug Therapy, Combination
- Endpoint Determination
- Female
- Humans
- Hydrochlorothiazide
(administration & dosage, adverse effects, therapeutic use)
- Hypertension
(complications, drug therapy)
- Imidazoles
(administration & dosage, adverse effects, therapeutic use)
- Male
- Middle Aged
- Tetrazoles
(administration & dosage, adverse effects, therapeutic use)
- Young Adult
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