1. Increased risk of left heart valve regurgitation associated with benfluorex use in patients with diabetes mellitus: a multicenter study
- Author
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Sylvestre Maréchaux, Dan Rusinaru, Pierre-Vladimir Ennezat, Yannick Jobic, Jacques Boulanger, Christophe Tribouilloy, Elise Arnalsteen, Patricia Reant, Stéphane Ederhy, Thierry Garban, Erwan Donal, Antoine Jeu, Pôle cardiovasculaire et thoracique, CHU Amiens-Picardie, Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement Hospitalier de l'Institut Catholique de Lille, Faculté Libre de Médecine de Lille (FLM), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Institut Catholique de Lille (ICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-UC Lille, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de Médecine Interne et Cardiologie, Centre Hospitalier de Beauvais, Service de Cardiologie, Centre Hospitalier de Compiègne, Service de cardiologie, Hôpital Cardiologique-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Universitaire G et R Laennec, Département de Cardiologie (CHRU - Cardio), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Faculté Libre de Médecine-UC Lille, Service de Cardiologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
MESH: Mitral Valve Insufficiency ,Male ,030204 cardiovascular system & hematology ,drugs ,MESH: Fenfluramine ,Coronary artery disease ,chemistry.chemical_compound ,MESH: Safety-Based Drug Withdrawals ,0302 clinical medicine ,[INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing ,MESH: Risk Factors ,MESH: Appetite Depressants ,Risk Factors ,Single-Blind Method ,030212 general & internal medicine ,Prospective Studies ,MESH: Aged ,2. Zero hunger ,Benfluorex ,MESH: Middle Aged ,Mitral Valve Insufficiency ,regurgitation ,MESH: Aortic Valve Insufficiency ,MESH: Follow-Up Studies ,Middle Aged ,3. Good health ,Europe ,medicine.anatomical_structure ,Echocardiography ,Cardiology ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Female ,Cardiology and Cardiovascular Medicine ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,medicine.medical_specialty ,MESH: Diabetes Mellitus ,Aortic Valve Insufficiency ,valves ,03 medical and health sciences ,Safety-Based Drug Withdrawals ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Appetite Depressants ,Fenfluramine ,medicine ,Diabetes Mellitus ,Product Surveillance, Postmarketing ,Humans ,MESH: Product Surveillance, Postmarketing ,Heart valve ,Aged ,MESH: Humans ,business.industry ,MESH: Single-Blind Method ,medicine.disease ,MESH: Male ,MESH: Prospective Studies ,chemistry ,Propensity score matching ,MESH: Echocardiography ,Observational study ,MESH: Europe ,business ,MESH: Female ,Body mass index ,Dyslipidemia ,Follow-Up Studies - Abstract
Background— Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least 3 months and in diabetic control subjects never exposed to the drug. Methods and Results— This reader-blinded, controlled study conducted in 10 centers in France between February 2010 and September 2011 prospectively included 376 diabetic subjects previously exposed to benfluorex who were referred by primary care physicians for echocardiography and 376 diabetic control subjects. Through the use of propensity scores, 293 patients and 293 control subjects were matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (odds ratio) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared with control subjects: 31.0% versus 12.9% (odds ratio, 3.55; 95% confidence interval, 2.03–6.21) for aortic and/or mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence interval, 2.46–11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio, 2.38; 95% confidence interval, 1.27–4.45) for mitral regurgitation. Conclusions— Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.
- Published
- 2012
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