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Efficacy and Safety of Incremental Dosing of a New Single-Pill Formulation of Perindopril and Amlodipine in the Management of Hypertension

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Abstract

Background

Angiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill combinations (SPCs) are increasingly recognized, so a dosage-adapted combination of perindopril and amlodipine was developed for the initial management of hypertension.

Objective

This randomized trial evaluated the blood pressure (BP)-lowering efficacy of four incremental doses of perindopril/amlodipine SPC in adults with mild-to-severe hypertension.

Methods

Eligible patients (N = 1617) were randomized to SPC perindopril 3.5 mg/amlodipine 2.5 mg (i.e., 3.5/2.5 mg) daily, uptitrating as required on a monthly basis up to 14/10 mg until BP < 140/90 mmHg (< 130/80 mmHg in patients with diabetes). The primary endpoint (proportion with controlled BP at each uptitrated dose) was evaluated at 6 months, and safety was evaluated at 9 months; 24-h ambulatory BP measurement and BP variability were also investigated. Control-arm participants (n = 1653) were randomized to irbesartan 150 mg daily, uptitrating over 3 months to irbesartan/hydrochlorothiazide 300/25 mg.

Results

Significant increases in BP control were observed with each dosage increment of perindopril/amlodipine, which was well tolerated, rising from 21% (3.5/2.5 mg) to 30% (7/5 mg), 37% (14/5 mg), and 42% (14/10 mg) after 1, 2, 3, and 6 months, respectively. Reductions in mean systolic and diastolic BP occurred with each incremental dose of perindopril/amlodipine. After 6 months, mean BP had fallen by 24.8/10.8 mmHg. Irbesartan-based therapy reduced clinic and 24-h BP similarly to perindopril/amlodipine, but perindopril/amlodipine reduced BP variability more in comparison.

Conclusions

Incremental uptitration with dosage-adapted perindopril/amlodipine SPC is a safe and effective strategy for managing hypertension.

Trial registration

EudraCT (No. 2006-005799-42).

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Author information

Authors and Affiliations

  1. Imperial Clinical Trials Unit, School of Public Health, Imperial College London, 1st Floor Stadium House, 68 Wood Lane, London, W12 7TA, UK

    Neil R. Poulter

  2. Stroke and Hypertension Unit, Connolly Hospital, Blanchardstown, Dublin, Ireland

    Eamon Dolan

  3. William Harvey Research Institute, Queen Mary University of London, London, UK

    Ajay K. Gupta

  4. Conway Institute, University College Dublin, Dublin, Ireland

    Eoin O’Brien

  5. NHLI, Imperial College London, London, UK

    Andrew Whitehouse & Peter S. Sever

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  1. Neil R. Poulter
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  4. Eoin O’Brien
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  6. Peter S. Sever
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Corresponding author

Correspondence to Neil R. Poulter.

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Funding

This study was funded by Servier. Medical writing and editorial support, under the guidance of the authors, was provided by John Plant (Servier).

Conflicts of interest

Neil Poulter has received financial support from several pharmaceutical companies that manufacture BP-lowering agents, for consultancy (Servier), research projects and staff (Pfizer, Servier), and arranging and speaking at education meetings (Astra Zeneca, Lri Therapharma, Napi, Servier, and Pfizer). He holds no stocks or shares in any such companies. In the last 3 years, Ajay Gupta has received financial support to attend a conference and an honorarium for a presentation from Servier, but these funds were for activities unrelated to this manuscript. During the conduct of this study, he was part of an independent safety and adjudication committee and received consulting fees for that work. Andrew Whitehouse has claimed travel expenses during the conduct of the study to attend study sites and the funder’s offices. Eamon Dolan, Eoin O’Brien, and Peter Sever have no conflicts of interest that are directly relevant to the content of this article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of national research committees and with the Helsinki declaration.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Poulter, N.R., Dolan, E., Gupta, A.K. et al. Efficacy and Safety of Incremental Dosing of a New Single-Pill Formulation of Perindopril and Amlodipine in the Management of Hypertension. Am J Cardiovasc Drugs 19, 313–323 (2019). https://doi.org/10.1007/s40256-018-00314-4

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  • DOI: https://doi.org/10.1007/s40256-018-00314-4

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