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Multicenter Randomized Double-Blind Comparison of Nebivolol plus HCTZ and Irbesartan plus HCTZ in the Treatment of Isolated Systolic Hypertension in Elderly Patients: Results of the NEHIS Study

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Abstract

Introduction

The present study was aimed at comparing the antihypertensive efficacy, tolerability, and side effects profile of nebivolol/hydrochlorothiazide (NH) vs irbesartan/hydrochlorothiazide (IH) combination in elderly patients with isolated systolic hypertension (ISH).

Methods

124 ISH patients aged 69.1 ± 5.1 years (mean ± SD) were enrolled by 13 general practitioners in Netherlands and Belgium and randomized in a double-blind fashion to receive either NH (5/12.5 mg day, n = 62) or IH (150/12.5 mg day, n = 62) for a 12-week period. The primary efficacy endpoint of the study was the comparison of the two combinations in terms of sitting office systolic blood pressure (BP) reduction after 12 weeks of treatment. In addition ambulatory BP, 24-h BP variability, tolerability, and safety profile were also investigated.

Results

122 patients were included in the intention-to-treat analysis. After 12 weeks of treatment the reduction of systolic BP with NH was significantly greater than IH (−25.8 ± 12 vs −21.2 ± 14 mm Hg, P < 0.03). Diastolic BP reduction was significantly greater with NH after 4 and 8 weeks of treatment but similar at the end of the study (or after 12 weeks). In contrast, the magnitude of the 24-h, daytime, and nighttime systolic and diastolic BP reduction was almost similar in the two groups, while heart rate reduction induced by NH was significantly (P < 0.001) greater during the 24-h, daytime, and nighttime period than that induced by IH. NH caused a reduction in 24-h BP variability significantly greater than IH (standard deviation −4.4 ± 2.7 vs −2.2 ± 5.1 mm Hg, P < 0.02, variation coefficient −2.0 ± 2.6 vs −0.3 ± 3.4%, P < 0.01). Both treatment regimens were well tolerated.

Conclusions

These data provide evidence that NH reduces office BP more than IH but has similar effects on 24-h BP. NH reduces 24-h systolic and diastolic BP variability more than IH, suggesting a greater protective effect on a variable known to adversely affect prognosis.

Trial Registration

EU clinical Trials Register identifier, 2010-023104-28.

Funding

Menarini International Operations Luxembourg.

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Acknowledgments

Sponsorship and article processing charges for this study were funded by Menarini International Opertations Luxembourg. The study was overseen by an independent academic steering committee. The authors had full access to all data and had final responsibility for the contents of the manuscript and the decision to submit it for publication. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Disclosures

Guido Grassi, Gino Seravalle, Gianmaria Brambilla, Raffaella Dell’Oro, Fosca Quarti, Francesco Fici, Luc Van Bortel, and Giuseppe Mancia have nothing to disclose.

Compliance with ethics guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. The protocol was approved by the Ethics Committee of the Hospital and the University of Antwerp, Edegem, Belgium (Trial registration, EudractCT Number: 2010-023104-28). Informed consent was obtained from all patients for included in the study.

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Authors and Affiliations

  1. Clinica Medica, Università Milano-Bicocca, Milan, Italy

    Guido Grassi, Gianmaria Brambilla, Raffaella Dell’Oro, Fosca Quarti Trevano, Francesco Fici & Giuseppe Mancia

  2. Clinica medica, Università Milano- Bioccca, Milan Italy and Istituto di Ricerca a Carattere Scientifico IRCCS Multimedica, Sesto San Giovanni, Milan, Italy

    Guido Grassi

  3. Istituto Auxologico Italiano IRCCS, Milan, Italy

    Gino Seravalle

  4. Clinical Pharmacology Research Unit, Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium

    Luc van Bortel

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  1. Guido Grassi
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Correspondence to Guido Grassi.

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Grassi, G., Seravalle, G., Brambilla, G. et al. Multicenter Randomized Double-Blind Comparison of Nebivolol plus HCTZ and Irbesartan plus HCTZ in the Treatment of Isolated Systolic Hypertension in Elderly Patients: Results of the NEHIS Study. Adv Ther 33, 2173–2187 (2016). https://doi.org/10.1007/s12325-016-0427-1

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