title: Frequency of drug-induced valvular heart disease in patients previously exposd to benfluorex: a multicentre prospective study.
abstract: OBJECTIVE
  The epidemiologic link between benfluorex use and an increased global frequency of left heart valve regurgitation has been well documented. However, no data linking previous drug exposure to the frequency of diagnosis of drug-induced valvular heart disease (DI-VHD) are available. The present study was conducted to address this issue.
  
  
  RESULTS
  This echocardiography reader-blinded, controlled study conducted in 10 centres between February 2010 and February 2012 prospectively included 835 subjects previously exposed to benfluorex referred by primary care physicians for echocardiography. Based on blinded off-line analysis, echocardiography findings were classified as: (i) DI-VHD⁺ for patients with an echocardiographic diagnosis of DI-VHD, (ii) inconclusive, and (iii) DI-VHD⁻ for patients without signs of DI-VHD. Fifty-seven (6.8%) patients exposed to benfluorex were classified as DI-VHD⁺, 733 (87.8%) patients were classified as DI-VHD⁻, and 45 (5.4%) were classified as inconclusive. Mitral and aortic DI-VHD were reported in 43 patients (5.1%) and 30 (3.6%) patients, respectively. Longer duration of exposure, female gender, smoking, and lower BMI were independently associated with a diagnosis of DI-VHD. Good inter-observer reproducibility was observed for the echocardiography classification (Kappa = 0.83, P < 0.00001).
  
  
  CONCLUSIONS
  About 7% of patients without a history of heart valve disease previously exposed to benfluorex present echocardiography features of DI-VHD. Further studies are needed to study the natural history of DI-VHD and to identify risk factors for the development of drug-induced valve lesions.
authors.affiliation: Pôle cardiovasculaire et thoracique, Centre Hospitalier Universitaire Amiens, Amiens, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tribouilloy
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Maréchaux
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jobic
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: Thierry
authors.initials: T
authors.lastname: Garban
authors.forename: Pierre-Vladimir
authors.initials: PV
authors.lastname: Ennezat
authors.forename: Michel
authors.initials: M
authors.lastname: Andréjak
authors.forename: Dan
authors.initials: D
authors.lastname: Rusinaru
mesh_terms: D000704:Analysis of Variance; D001022:Aortic Valve Insufficiency / Q000139:chemically induced*; D001067:Appetite Depressants / Q000009:adverse effects*; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000188:drug therapy; D050171:Dyslipidemias / Q000188:drug therapy; D004452:Echocardiography; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000139:chemically induced*; D009765:Obesity / Q000188:drug therapy; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D001067:Appetite Depressants; D000960:Hypolipidemic Agents; D005277:Fenfluramine; C001584:benfluorex
keywords: Benfluorex; Drug-induced valvular disease; Echocardiography