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Triple-combination therapy in the treatment of hypertension: a review of the evidence

Journal of Human Hypertension volume 31, pages 501–510 (2017)Cite this article

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Abstract

Hypertension is a serious public health concern with inadequate control of blood pressure (BP) worldwide. Contributing factors include low efficacy of drugs, underuse of combination therapies, irrational combinations, physicians’ therapeutic inertia and poor adherence to treatment. Current guidelines recommend the use of initial (dual) combination therapy in high-risk patients for immediate BP response, better short- and long-term BP control, and continued/improved patient adherence. This article aims to review the existing evidence of triple-combination therapies with respect to efficacy, safety and adherence to treatment. It is estimated that three drugs are required to achieve BP control in approximately one-fourth to one-third of patients. Randomised controlled trials (RCTs) have shown that triple combinations of amlodipine/valsartan/hydrochlorothiazide, amlodipine/olmesartan/hydrochlorothiazide and amlodipine/telmisartan/hydrochlorothiazide produce greater BP reductions, with greater proportions of patients achieving BP control compared with dual therapies. Further evidence also demonstrates that triple-combination therapy is efficacious for moderate to severe hypertension, with substantial additional BP reduction over dual regimens. Both RCTs and post-marketing observational studies have shown consistent and comparable efficacy in both the general population and high-risk hypertensive subgroups. Triple therapies are generally well tolerated with adverse event profiles similar to dual regimens. In addition, fixed-dose combinations used as single pill improve patient adherence leading to better long-term BP control. Depending on regional circumstances, they may also be cost effective. Thus, single-pill triple combinations of different classes of drugs with complementary mechanisms of action help to treat patients to goal with improved efficacy and better adherence to treatment.

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Acknowledgements

We would like to acknowledge medical writing support from Dr Krishna Swetha Gummuluri, Novartis Healthcare Pvt. Ltd., Hyderabad, India.

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Authors and Affiliations

  1. Schwerpunktpraxis Kardiologie, Hypertoniezentrum Bonn, Bonn, Germany

    R Düsing

  2. Division of Clinical Pathophysiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

    B Waeber

  3. Scientific Medical Department, General Medicine Unit Treviglio Hospital, ASST Bergamo Ovest, Bergamo, Italy,

    M Destro

  4. Novartis Pharma AG, Basel, Switzerland

    C Santos Maia & P Brunel

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Correspondence to R Düsing.

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Competing interests

RD has received honoraria for scientific lectures and financial support for conducting clinical studies from Novartis, Servier, Berlin Chemie and UCB Pharma. MD has received consulting and lecture fees and research grants from Boehringer Ingelheim, AstraZeneca, Servier, Menarini IFR, Schering-Plough, Guidotti, Pfizer, Knoll, Bayer, Chiesi, Daiichi-Sankyo, Merck Sharpe & Dohme and Malesci. MD has also received research support as a study investigator from Novartis Pharma AG and has been a speaker at scientific meetings organised by Novartis. BW has received consulting and lecture fees from Novartis, Pfizer, Menarini and Servier. PB is an employee of Novartis Pharma are thus eligible for Novartis stocks and stock options. CSM was an employee of Novartis at the time of manuscript preparation.

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Düsing, R., Waeber, B., Destro, M. et al. Triple-combination therapy in the treatment of hypertension: a review of the evidence. J Hum Hypertens 31, 501–510 (2017). https://doi.org/10.1038/jhh.2017.5

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