title: Increased risk of left heart valve regurgitation associated with benfluorex use in patients with diabetes mellitus: a multicenter study.
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  Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions.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.
  
  
  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.
authors.affiliation: INSERM U 1088 and University Hospital, Amiens, France, Department of Cardiology, Avenue René Laënnec, 80054 Amiens Cedex 1, France. tribouilloy.christophe@chu-amiens.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Tribouilloy
authors.forename: Dan
authors.initials: D
authors.lastname: Rusinaru
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Maréchaux
authors.forename: Antoine
authors.initials: A
authors.lastname: Jeu
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ederhy
authors.forename: Erwan
authors.initials: E
authors.lastname: Donal
authors.forename: Patricia
authors.initials: P
authors.lastname: Réant
authors.forename: Elise
authors.initials: E
authors.lastname: Arnalsteen
authors.forename: Jacques
authors.initials: J
authors.lastname: Boulanger
authors.forename: Pierre-Vladimir
authors.initials: PV
authors.lastname: Ennezat
authors.forename: Thierry
authors.initials: T
authors.lastname: Garban
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jobic
mesh_terms: D000368:Aged; D001022:Aortic Valve Insufficiency / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D001067:Appetite Depressants / Q000009:adverse effects; D003920:Diabetes Mellitus / Q000453:epidemiology; D004452:Echocardiography; D005060:Europe / Q000453:epidemiology; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D011446:Prospective Studies; D012307:Risk Factors; D056737:Safety-Based Drug Withdrawals; D016037:Single-Blind Method
chemical_list: D001067:Appetite Depressants; D005277:Fenfluramine; C001584:benfluorex