title: Fenfluramine and phentermine and cardiovascular findings: effect of treatment duration on prevalence of valve abnormalities.
abstract: BACKGROUND
  The combination of fenfluramine and phentermine was a widely used obesity treatment before the withdrawal of fenfluramine for an association with heart valve regurgitation. The prevalence and clinical significance of regurgitation among patients treated with these medications has yet to be fully established.
  
  
  RESULTS
  To evaluate the potential association between the duration of treatment and the prevalence of heart valve abnormalities, we examined 1163 patients who had taken fenfluramine-phentermine and 672 control patients who had not taken the drug combination within 5 years. Mild or greater aortic regurgitation was present in 8.8% of treated patients and 3.6% of control patients (P<0.001). Moderate or greater mitral regurgitation was present in 2.6% of treated patients and 1.5% of control patients (P=0.18). The adjusted odds ratio compared with controls of aortic regurgitation of mild or greater severity increased according to duration of treatment: 90 to 180 days, 1.5 (P=0.23); 181 to 360 days, 2.4 (P=0.002); 361 to 720 days, 4.6 (P<0.001); >720 days, 6.2 (P<0.001).
  
  
  CONCLUSIONS
  This is the largest study to demonstrate a relation between the length of treatment with fenfluramine-phentermine and the prevalence of valvular abnormalities. These findings suggest that valvular abnormalities in patients who took fenfluramine-phentermine primarily involve those who had taken these medications for >6 months and predominantly results in mild aortic regurgitation. The valve regurgitation identified by this study was not accompanied by significant differences in cardiovascular symptoms nor physical findings other than a higher prevalence of heart murmurs.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, NC 27710, USA. james.jollis@duke.edu
authors.forename: J G
authors.initials: JG
authors.lastname: Jollis
authors.forename: C K
authors.initials: CK
authors.lastname: Landolfo
authors.forename: J
authors.initials: J
authors.lastname: Kisslo
authors.forename: G D
authors.initials: GD
authors.lastname: Constantine
authors.forename: K D
authors.initials: KD
authors.lastname: Davis
authors.forename: T
authors.initials: T
authors.lastname: Ryan
mesh_terms: D001022:Aortic Valve Insufficiency / Q000139:chemically induced* / Q000150:complications / Q000000981:diagnostic imaging; D001067:Appetite Depressants / Q000009:adverse effects*; D016022:Case-Control Studies; D004338:Drug Combinations; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000139:chemically induced* / Q000150:complications / Q000000981:diagnostic imaging; D010645:Phentermine / Q000009:adverse effects*; D015995:Prevalence; D011446:Prospective Studies; D014463:Ultrasonography
chemical_list: D001067:Appetite Depressants; D004338:Drug Combinations; D005277:Fenfluramine; D010645:Phentermine