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Use of antihistamines and risk of ventricular tachyarrhythmia: a nested case-control study in five European countries from the ARITMO project

  • Pharmacoepidemiology and Prescription
  • Published:
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Abstract

Purpose

After regulatory restrictions for terfenadine and astemizole in ‘90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines.

Methods

A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997–2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression.

Results

For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6–7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7–7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1–14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1–10.8) and PHARMO (ORadj, 4.6; 1.3–16.2).

Conclusions

The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

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Funding

The current study is part of the EU-funded ARITMO study which aimed to assess the utilisation and arrhythmogenic potential of anti-infectives, antihistamines and antipsychotics. ARITMO is a Research and Development project funded by the Health Area of the European Commission under the VII Framework Program (FP7/2007-2013), under grant agreement no. 241679-the ARITMO project.

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

    Elisabetta Poluzzi, A. Koci & F. De Ponti

  2. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy

    I. Diemberger & G. Boriani

  3. Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands

    M. De Ridder, A. Oteri, M. C. J. Sturkenboom & G. Trifirò

  4. Regione Emilia Romagna Health Authority, Bologna, Italy

    M. Clo

  5. Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy

    A. Oteri & G. Trifirò

  6. Health Search, Italian College of General Practitioners, Florence, Italy

    S. Pecchioli

  7. Regional Agency for Healthcare Services of Tuscany, Florence, Italy

    S. Pecchioli

  8. PHARMO Institute for Drug Outcomes Research, Utrecht, Netherlands

    I. Bezemer

  9. Leibniz Institute for Epidemiology and Prevention Research - BIPS, Bremen, Germany

    T. Schink

  10. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark

    S. Pilgaard Ulrichsen

  11. Cardiology Division, Department of Diagnostics, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy

    G. Boriani

Authors
  1. Elisabetta Poluzzi
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  2. I. Diemberger
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  3. M. De Ridder
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  4. A. Koci
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  5. M. Clo
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  6. A. Oteri
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  7. S. Pecchioli
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  8. I. Bezemer
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  9. T. Schink
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  10. S. Pilgaard Ulrichsen
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  11. G. Boriani
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  12. M. C. J. Sturkenboom
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  13. F. De Ponti
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  14. G. Trifirò
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Corresponding author

Correspondence to Elisabetta Poluzzi.

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Conflict of interest

EP, IG, MdR, AK, MC, AO, SP, IB, SPU, FDP, and GT declare no additional support from any organisation. TS is working in departments that occasionally perform studies funded by pharmaceutical industries (Bayer, Celgene, GlaxoSmithKline, Mundipharma, Novartis, Purdue Pharma, Sanofi-Aventis, Sanofi Pasteur MSD and STADA). GB received fees for lectures from Boehringer. MS is heading a research unit that holds unconditional research contracts with some pharmaceutical companies (EliLilly, Pfizer, AstraZeneca), none related to this study.

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For this type of study, formal consent is not required.

Statement on the welfare of animals

This article does not contain any studies with animals performed by any of the authors.

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Poluzzi, E., Diemberger, I., De Ridder, M. et al. Use of antihistamines and risk of ventricular tachyarrhythmia: a nested case-control study in five European countries from the ARITMO project. Eur J Clin Pharmacol 73, 1499–1510 (2017). https://doi.org/10.1007/s00228-017-2317-0

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  • DOI: https://doi.org/10.1007/s00228-017-2317-0

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