Pulmonary hypertension associated with benfluorex exposure

Laurent Savale, Marie-Camille Chaumais, Vincent Cottin, Emmanuel Bergot, Irène Frachon, Grégoire Prevot, Christophe Pison, Claire Dromer, Patrice Poubeau, Nicolas Lamblin, Gilbert Habib, Martine Reynaud-Gaubert, Arnaud Bourdin, Olivier Sanchez, Pascale Tubert-Bitter, Xavier Jaïs, David Montani, Olivier Sitbon, Gérald Simonneau, Marc Humbert

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.

The aim of this study is to report clinical and haemodynamic characteristics of patients suffering of pulmonary hypertension associated with benfluorex exposure identified by the French pulmonary hypertension network.

Eighty five cases of pulmonary hypertension associated with benfluorex exposure were identified by the French pulmonary hypertension network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary pulmonary hypertension. 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 pulmonary hypertension was identified in 20/70 (30%) patients with pre-capillary pulmonary hypertension. A quarter of patients in this current series showed co-existing pulmonary hypertension 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 pulmonary arterial hypertension