Benfluorex and unexplained valvular heart disease: a case-control study.
BACKGROUND
Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation.


METHODS
We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1(st) 2003 and June 30(th) 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051). Patients with either a primary cause (degenerative, known rheumatic heart disease, infectious endocarditis, congenital, radiation-induced valvular disease, associated connective and/or vasculitis disease, trauma, tumor) or a secondary (functional) cause were considered as having an "explained" mitral regurgitation. Other patients were considered as having an "unexplained" mitral regurgitation and were included as cases. For each case, two controls were matched for gender and for the closest date of birth, among a list of patients with an "explained" mitral regurgitation. Drug exposures were assessed blindly regarding the case or control status, through contacts with patients, their family and/or their physicians.


RESULTS
Out of the 682 eligible patients, 27 cases and 54 matched controls were identified. The use of benfluorex was reported in 22 patients: 19 of the 27 cases, versus 3 of the 54 controls, odds-ratio 17.1 (3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use.


CONCLUSIONS
The use of benfluorex is associated with unexplained mitral regurgitation.
Frachon
Irène
I
Université Européenne de Bretagne, Brest, France. irene.frachon@chu-brest.fr
Etienne
Yves
Y
Jobic
Yannick
Y
Le Gal
Grégoire
G
Humbert
Marc
M
Leroyer
Christophe
C
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects / Q000031:analogs & derivatives*; D006349:Heart Valve Diseases / Q000139:chemically induced* / Q000209:etiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000139:chemically induced / Q000209:etiology; D016017:Odds Ratio; D012189:Retrospective Studies; D016037:Single-Blind Method
D000960:Hypolipidemic Agents; D005277:Fenfluramine; C001584:benfluorex
N Engl J Med. 1998 Sep 10;339(11):725-32
9731088
Eur Respir J. 2009 Mar;33(3):684-8
19251806
N Engl J Med. 1998 Sep 10;339(11):719-24
9731087
Lancet. 2009 Aug 15;374(9689):577-85
19683643
N Engl J Med. 2007 Jan 4;356(1):29-38
17202453
Fundam Clin Pharmacol. 2006 Dec;20(6):577-8
17109650
N Engl J Med. 2007 Jan 4;356(1):39-46
17202454
Mayo Clin Proc. 2002 Dec;77(12):1280-6
12479512
Rev Esp Cardiol. 2003 Feb;56(2):215-6
12605770
N Engl J Med. 1997 Aug 28;337(9):581-8
9271479
N Engl J Med. 1998 Sep 10;339(11):713-8
9731086
N Engl J Med. 2007 Jan 4;356(1):6-9
17202450
Circulation. 2000 Dec 5;102(23):2836-41
11104741
Am J Cardiol. 1999 Mar 15;83(6):897-902
10190406
Lancet. 2009 Apr 18;373(9672):1382-94
19356795
BMC Med. 2008 Nov 06;6:34
18990200
N Engl J Med. 1996 Aug 29;335(9):609-16
8692238