Chest
Brenot Memorial Symposium on the Pathogenesis of Primary Pulmonary HypertensionPrimary Pulmonary Hypertension Associated With the Use of Fenfluramine Derivatives
Section snippets
Anorexigens and PPH: A Historical Review Aminorex PPH
Between 1967 and 1972, in Austria, Germany, and Switzerland, the incidence of cases of severe PH increased sharply.6 Among the 582 cases of PH observed in these countries during this period, 62% of affected patients had a history of aminorex intake (alone or in association with other anorexic drugs). In this epidemic of severe PH, the role of aminorex was very quickly suspected because of the evidence of a close geographic as well as temporal relationship between the intake of aminorex and the
Patients and Methods
From 1986 to September 1997, 62 patients with fenfluramine-associated PPH were evaluated in our center for pulmonary vascular disease. Pulmonary hypertension was defined as a mean resting pulmonary artery pressure >25 mm Hg during right heart catheterization, with a mean pulmonary wedge pressure < 12 mm Hg. Secondary causes of PH were excluded. We also excluded patients with PPH and associated portal hypertension and HIV infection. All the fenfluramine-associated PPH patients had a history of
Results
The main clinical characteristics of the two groups of patients with PPH are shown in Table 1. Patients were mostly women, with a female:male ratio of 30:1 in the two groups. This was in sharp contrast with the 1:1.7 sex ratio reported in the National Institutes of Health Registry9 and in our cohort.10 Patients with fenfluramine-associated PPH and control PPH were very similar in terms of New York Heart Association functional class, symptoms, and associated conditions. Fenfluramine-associated
Mechanisms of Fenfluramine-Associated PPH: The Serotonin Hypothesis
The pathogenetic mechanisms of PPH associated with fenfluramine is unknown. However, it appears that alteration of the serotonin (5-hydroxytryptamine [5-HT]) pathway might be a common denominator of fenfluramine- or amphetamine-associated PPH. Serotonin is known to be a powerful pulmonary vasoconstrictor and can induce platelet aggregation.11 Moreover, recent studies indicate that serotonin is also a potent factor stimulating pulmonary smooth muscle proliferation.12 Clinical and experimental
REFERENCES (27)
- et al.
Primary pulmonary hypertension in HIV infection
Chest
(1991) Primary pulmonary hypertension: case series from France
Chest
(1994)- et al.
Increased plasma serotonin in primary pulmonary hypertension
Am J Med
(1995) - et al.
Primary pulmonary hypertension in a patient with a familial platelet storage pool disease
Am J Med
(1990) - et al.
Appetite suppression by commonly used drugs depends more on 5-HT receptors but not on 5-HT availability
Trends Pharmacol Sci
(1997) - et al.
Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics
Gastroenterology
(1991) - et al.
Pulmonary hypertension in patients with human immunodeficiency virus infection: comparison with primary pulmonary hypertension
Circulation
(1994) - et al.
Appetite-suppressant drugs and the risk of primary pulmonary hypertension
N Engl J Med
(1996) Primary pulmonary hypertension
Wien Z Inn Med
(1969)Chronishe pulmonale hypertonie vascularen Ursprungs, plexogene pulmonale arteriopathei und der appetizügler aminorex
Schweiz Med Wochenschr
(1985)
Pulmonary hypertension and fenfluramine
BMJ
Primary pulmonary hypertension and fenfluramine use
Br Heart J
Primary pulmonary hypertension: a national prospective study
Ann Intern Med
Cited by (104)
Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future
2016, Pharmacology and TherapeuticsCitation Excerpt :There is a large body of compelling data from animal and human studies supporting a role for serotonin (5-HT) in the pathophysiology of PAH. The association of anorectic agents with PAH sets the scene (Delcroix et al., 1998; Simonneau et al., 1998). Both aminorex and fenfluramine are serotonin transporter (SERT) substrates and act as indirect serotinergic agonists (Rothman et al., 1999).
Prognostic value of acute vasodilator response in pulmonary arterial hypertension: Beyond the "classic" responders
2015, Journal of Heart and Lung TransplantationEpidemiology of pulmonary arterial hypertension
2013, Clinics in Chest MedicineCitation Excerpt :The study also identified a high frequency of anorectic agent use among patients with other associated forms of PAH (eg, collagen vascular disease), suggesting that these drugs might precipitate disease when combined with other risk factors.129 In a series of 62 patients evaluated over a 10-year period at a single center in France, the interval between the initial exposure to fenfluramine and the development of dyspnea was approximately 4 years.130 In the multicenter French national registry from 2002 to 2003, anorexigen-associated PAH was diagnosed within 2 years of drug exposure in 24% of cases, between 2 and 5 years in 32% and after more than 5 years following drug exposure in 44%.12
Drugs induced pulmonary arterial hypertension
2013, Presse MedicaleCitation Excerpt :In conclusion, fenfluramine-induced PAH patients share clinical, functional, hemodynamic and genetic features with idiopathic PAH patients, as well as similar overall survival rates. These observations suggest that fenfluramine derivatives may act as a trigger for PAH without influencing its clinical course [7,16]. Benfluorex is a benzoate ester that shares similar structural and pharmacological characteristics with fenfluramine derivatives [17].
Classification of Pulmonary Hypertension
2012, Heart Failure ClinicsPulmonary Arterial Hypertension
2011, Current Problems in Cardiology