Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus

Authors

  • Alain Weill,

    Corresponding author
    1. Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, Paris, France
    • Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, 50 Avenue du Pr André Lemierre, 75986 Paris Cedex 20, France.
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  • Michel Païta,

    1. Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, Paris, France
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  • Philippe Tuppin,

    1. Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, Paris, France
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  • Jean-Paul Fagot,

    1. Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, Paris, France
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  • Anke Neumann,

    1. Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, Paris, France
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  • Dominique Simon,

    1. Service de Diabétologie, Groupe Hospitalier Pitié Salpêtrière, Paris, France
    2. Centre de recherche en Epidémiologie et Santé des Populations, INSERM Villejuif, France
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  • Philippe Ricordeau,

    1. Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, Paris, France
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  • Jean-Louis Montastruc,

    1. Service de Pharmacologie Clinique, Unité de Pharmacoépidémiologie (EA 3696 et INSERM) Centre Hospitalier Universitaire et Faculté de Médecine de Toulouse, Toulouse, France
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  • Hubert Allemand

    1. Direction générale, Caisse Nationale de l'Assurance Maladie, Paris, France
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Abstract

Purpose

To evaluate and quantify in diabetic patients treated with benfluorex in France, a fenfluramine-derivated product, a possible increase in risk of valvular heart disease, previously suggested by several published case reports.

Methods

This was a French comparative cohort study using data from two large national linked databases, health insurance system (SNIIRAM) and hospitalization (PMSI). Patients aged 40–69 years with reimbursement for oral antidiabetic and/or insulin in 2006 were eligible. Exposed patients were defined as patients with at least one benfluorex reimbursement in 2006. Selected admission diagnoses of interest in 2007 and 2008 PMSI databases were valvular insufficiency for any cause, mitral insufficiency, aortic insufficiency, and valvular replacement surgery with cardiopulmonary bypass. Relative risks (RR) were adjusted on gender, age, and history of chronic cardiovascular disease.

Results

A total of 1 048 173 diabetic patients were included, with 43 044 (4.1%) exposed to benfluorex. The risk of hospitalization in 2007 and 2008 for any cardiac valvular insufficiency was higher in the benfluorex group: crude RR = 2.9 [95% confidence interval 2.2–3.7] and adjusted RR = 3.1 [2.4–4.0], with a lower risk for patients with lower cumulative dose of benfluorex. Adjusted RR for mitral insufficiency and aortic insufficiency admissions were 2.5 [1.9–3.7] and 4.4 [3.0–6.6], respectively. Adjusted RR for valvular replacement surgery was 3.9 [2.6–6.1].

Conclusions

Benfluorex in diabetic patients was significantly associated with hospitalization for valvular heart disease in the 2 years following benfluorex exposure. Linkage between SNIIRAM and PMSI databases is in France a valuable tool to quantify the risk of serious adverse drug reactions. Copyright © 2010 John Wiley & Sons, Ltd.

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