Pulmonary hypertension associated with benfluorex exposure

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

doi:10.1183/09031936.00188611

Cited by 79 publications

(51 citation statements)

References 35 publications

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“…This was especially shown with anorectic agents. The presence of other risk factors associated with the disease has been reported in a relatively high proportion of patients exposed to fenfluramine and derivatives [24,26]. Moreover, in this population of PAH associated with anorexigens, the proportion of patients carrying the BMPR2 mutation has been found to be the same as patients with idiopathic PAH [25].…”

Section: Discussionmentioning

confidence: 60%

“…Experience with anorectic agents has shown that the time to onset of pulmonary vascular damage after initiation of treatment can sometimes be very long (median .5 years) and can occur away from the cessation of exposure [24,25]. This property, combined with a small proportion of patients affected by the side effect, partly explained late recognition of the role of some drugs in the emergence of new cases of PAH.…”

Section: Discussionmentioning

confidence: 99%

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Pulmonary arterial hypertension in patients treated with interferon

et al. 2014

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Isolated cases of pulmonary arterial hypertension (PAH) in patients treated with interferon (IFN) a or b have been reported in the literature.The aim of this study was to describe all consecutive cases of PAH patients with a history of IFN exposure identified in the French reference centre for severe pulmonary hypertension between 1998 and 2012.A total of 53 patients with PAH and a history of IFN therapy were identified. 48 patients had been treated with IFNa for chronic hepatitis C. Most of them had portal hypertension (85%) and 56% had HIV coinfection. Five additional patients had been treated with IFNb for multiple sclerosis. The diagnosis of PAH was made within 3 years after IFN therapy in 66% of patients. Repeated haemodynamic assessment was available in 13 out of 16 patients exposed to IFN after the diagnosis of PAH. Increased pulmonary vascular resistance .20% was observed in 11 out of 13 cases (median 43% increase; IQR 32-67%). In five of these patients, IFN withdrawal resulted in spontaneous haemodynamic improvement.This retrospective analysis suggests that IFN therapy may trigger PAH. However, most of these patients had other risk factors for PAH. A prospective case-control study is necessary to definitively establish a link between IFN exposure and PAH. @ERSpublications Clinical data suggest that interferon therapy may be a trigger for pulmonary arterial hypertension

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Pulmonary arterial hypertension in patients treated with interferon

et al. 2014

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“…A possible association can be suspected, for example, for drugs with similar mechanisms of action as those in the definite or likely category but which have not yet been studied, such as drugs used to treat attention deficit disorder. Definite clinical associations are listed among APAH in Table 4 and the risk level of different drugs and toxins are listed in Table 7 [6,[14][15][16].…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

et al. 2015

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Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

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“…A causative role has been proposed for several anorexigens including a recent report on Benfluorex in France [29], and selective serotonine re uptake inhibitors in pregnant women that result in pulmonary arterial hypertension of the newborns. Il licit drugs such as cocaine and amphethaminelike drugs show a possible association.…”

Section: Drugs and Toxinsmentioning

confidence: 99%

Pulmonary hypertension: Classification and pathobiology

2014

Cardiovasc Med

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SummaryPulmonary hypertension is defined as an increase of the mean pulmonary arterial pressure above 25 mm Hg and, as such, the diagnosis requires invasive haemo dynamic measurement by right heart catheterisation. More than just a single disease, pulmonary hyperten sion is an umbrella term that includes many different disorders and pathophysiological entities. However, most forms of pulmonary hypertension share a final common pathway, in particular the trias of vasocon striction, microthrombosis and vascular remodelling. The classification of pulmonary hypertension has been subjected to many changes within the last decade. At the same time, major achievements in our understand ing of the complex pathobiology have been made. Here, these developments are discussed in the light of the re cently published report from the fifth World Sympo sium on pulmonary hypertension. Definition and haemodynamicsPulmonary arterial pressure (PAP) is a function of car diac output, left atrial pressure and pulmonary vascu lar resistance. The pulmonary circulation is a lowpres sure system and the mean pulmonary arterial pressure (mPAP) does not exceed 20 mm Hg in healthy individ uals [1]. Pulmonary hypertension is defined as an in crease of the mPAP above 25 mm Hg. Pressure values ranging from 21 to 24 mm Hg have been associated with a high risk to develop overt pulmonary hyperten sion in a subgroup of patients, for example those with connective tissue disease [2], but otherwise these pa tients are not well defined and not much data exist on the prognostic and therapeutic consequences. Use of the term "borderline pulmonary hypertension" is thus not recom mended [3]. Increasing age [4] and body weight [5] have been associ ated with a rise of systolic pulmo nary arterial pressure (sPAP) and might explain the gap between nor mal mPAP and pulmonary hyper tension.The presence of pulmonary hypertension might be determined by echocardiography, which, depending on the underlying cause of elevated pulmonary pressure, provides an excellent screening tool. However, sensitiv ity and specificity of this method is limited [6]. Diagno sis is thus confirmed by invasive haemodynamic as sessment with right heart catheterisation at rest. An inadequate elevation of pulmonary pressure upon ex ercise has been part of former definitions of pulmonary hypertension but, due to lack of standardisation, is no longer a criterion.The differentiation of pulmonary hypertension due to left heart disease from the other forms is crucial. As suggested by guidelines, the pulmonary arterial wedge pressure (PAWP, also known as "wedge pressure") is used to estimate left atrial pressure in clinical practice. In healthy subjects, PAWP reflects left atrial pressure, which is extensively determined by left ventricular enddiastolic pressure (LVEDP). Several conditions in terfere with this assumption and may lead to misclas sification of pulmonary hypertension. Since pulmonary vessels are not stiff pipes but rather compressible tubes, an increase of the alveolar pressure (e.g., ...

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Pulmonary hypertension associated with benfluorex exposure

Cited by 79 publications

References 35 publications

Pulmonary arterial hypertension in patients treated with interferon

Pulmonary arterial hypertension in patients treated with interferon

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

Pulmonary hypertension: Classification and pathobiology

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