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Efficacy and Safety of Triple Antihypertensive Therapy with the Olmesartan/Amlodipine/Hydrochlorothiazide Combination

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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: 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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Acknowledgements

This study was designed and sponsored by Daiichi Sankyo Europe GmbH, Munich, Germany. Prof. Lars Christian Rump served as Coordinating Investigator and Medical Expert for the study. Medical writing assistance during the preparation of this manuscript was funded by Daiichi Sankyo Europe GmbH and provided by Faysal Riaz, PhD, of inScience Communications, Springer Healthcare, Chester, UK.

Prof. Massimo Volpe has participated in advisory boards and received honoraria for lectures from Daiichi Sankyo and Novartis Pharma. Prof. Lars Christian Rump has received honoraria from Daiichi Sankyo for lectures and consultancy work.

The authors thank all the investigators, study nurses and coordinators who participated in the study for their work.

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Authors and Affiliations

  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

    Massimo Volpe

  2. IRCCS Neuromed, Pozzilli, Italy

    Massimo Volpe

  3. Department of Internal Medicine/Nephrology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Lars Christian Rump

  4. Daiichi Sankyo Europe GmbH, Munich, Germany

    Bettina Ammentorp & Petra Laeis

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  1. Massimo Volpe
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Correspondence to Massimo Volpe.

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Volpe, M., Rump, L.C., Ammentorp, B. et al. Efficacy and Safety of Triple Antihypertensive Therapy with the Olmesartan/Amlodipine/Hydrochlorothiazide Combination. Clin Drug Investig 32, 649–664 (2012). https://doi.org/10.1007/BF03261919

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