Pulmonary hypertension associated with benfluorex exposure.
Laurent Savale
(1, 2)
,
Marie-Camille Chaumais
(2)
,
Vincent Cottin
(3, 4)
,
Emmanuel Bergot
(5)
,
Irène Frachon
(6, 7)
,
Grégoire Prevot
,
Christophe Pison
(8)
,
Claire Dromer
(9)
,
Patrice Poubeau
(10)
,
Nicolas Lamblin
(11)
,
Gilbert Habib
(12)
,
Martine Reynaud-Gaubert
(13)
,
Arnaud Bourdin
(14)
,
Olivier Sanchez
(15)
,
Pascale Tubert-Bitter
(16)
,
Xavier Jaïs
(1, 2)
,
David Montani
(1, 2)
,
Olivier Sitbon
(1, 2)
,
Gérald Simonneau
(1, 2)
,
Marc Humbert
(2)
1
UP11 -
Université Paris-Sud - Paris 11
2 Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique
3 Department of Pneumology [Lyon]
4 Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL]
5 Service de pneumologie [CHU Caen]
6 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
7 DMIP - Brest - Département de Médecine Interne et Pneumologie [Brest]
8 Clinique de pneumologie
9 Service de chirurgie thoracique
10 Service de Pneumologie et Maladies Infectieuses
11 Hôpital cardiologique
12 Service de cardiologie
13 Service de chirurgie thoracique
14 Service de pneumologie (Montpellier)
15 HEGP - Hôpital Européen Georges Pompidou [APHP]
16 CESP - Centre de recherche en épidémiologie et santé des populations
2 Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique
3 Department of Pneumology [Lyon]
4 Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL]
5 Service de pneumologie [CHU Caen]
6 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
7 DMIP - Brest - Département de Médecine Interne et Pneumologie [Brest]
8 Clinique de pneumologie
9 Service de chirurgie thoracique
10 Service de Pneumologie et Maladies Infectieuses
11 Hôpital cardiologique
12 Service de cardiologie
13 Service de chirurgie thoracique
14 Service de pneumologie (Montpellier)
15 HEGP - Hôpital Européen Georges Pompidou [APHP]
16 CESP - Centre de recherche en épidémiologie et santé des populations
Laurent Savale
- Function : Author
- PersonId : 761036
- ORCID : 0000-0002-6862-8975
- IdRef : 098817345
Grégoire Prevot
- Function : Author
Christophe Pison
- Function : Author
- PersonId : 766182
- ORCID : 0000-0002-2152-6461
- IdRef : 066846692
Gilbert Habib
- Function : Author
- PersonId : 757774
- ORCID : 0000-0003-3899-9983
- IdRef : 060822791
Arnaud Bourdin
- Function : Author
- PersonId : 975030
- ORCID : 0000-0002-4645-5209
- IdRef : 070160228
Olivier Sanchez
- Function : Author
- PersonId : 762026
- ORCID : 0000-0003-1633-8391
- IdRef : 123454395
Pascale Tubert-Bitter
- Function : Author
- PersonId : 759405
- ORCID : 0000-0003-4942-7753
David Montani
- Function : Author
- PersonId : 765451
- ORCID : 0000-0002-9358-6922
- IdRef : 092632580
Olivier Sitbon
- Function : Author
- PersonId : 763553
- ORCID : 0000-0002-1942-1951
- IdRef : 081152221
Marc Humbert
- Function : Author
- PersonId : 756837
- ORCID : 0000-0003-0703-2892
- IdRef : 071559426
Abstract
Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH). The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network. 85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement. The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.