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Adverse effects of benfluorex on heart valves and pulmonary circulation.
- Source :
-
Pharmacoepidemiology and drug safety [Pharmacoepidemiol Drug Saf] 2014 Jul; Vol. 23 (7), pp. 679-86. Date of Electronic Publication: 2014 May 10. - Publication Year :
- 2014
-
Abstract
- Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of its metabolites, norfenfluramine. The 5-HT2B receptor, expressed on heart valves, acts as culprit receptor for drug-induced valvular heart disease (VHD). Stimulation of this receptor leads to the upregulation of target genes involved in the proliferation and stimulation of valvular interstitial cells through different intracellular pathways. Valve lesions essentially involve the mitral and/or aortic valves. The randomised prospective REGULATE trial shows a threefold increase in the incidence of valvular regurgitation in patients exposed to benfluorex. A cross-sectional trial shows that about 7% of patients without a history of VHD previously exposed to benfluorex present echocardiographic features of drug-induced VHD. The excess risks of hospitalisation for cardiac valvular insufficiency and of valvular replacement surgery were respectively estimated to 0.5 per 1000 and 0.2 per 1000 exposed patients per year. Recent data strongly suggest an aetiological link between benfluorex exposure and pulmonary arterial hypertension (PAH). The PAH development may be explained by serotonin, which creates a pulmonary vasoconstriction through potassium-channel blockade. Further studies should be conducted to determine the subsequent course of benfluorex-induced VHD and PAH, and to identify genetic, biological and clinical factors that determine individual susceptibility to developing such adverse effects.<br /> (Copyright © 2014 John Wiley & Sons, Ltd.)
- Subjects :
- Echocardiography
Fenfluramine adverse effects
Fenfluramine metabolism
Heart Valve Diseases epidemiology
Heart Valve Diseases physiopathology
Heart Valves drug effects
Heart Valves physiopathology
Humans
Hypertension, Pulmonary epidemiology
Hypertension, Pulmonary physiopathology
Hypolipidemic Agents adverse effects
Norfenfluramine adverse effects
Norfenfluramine metabolism
Pulmonary Circulation drug effects
Randomized Controlled Trials as Topic
Receptor, Serotonin, 5-HT2B drug effects
Receptor, Serotonin, 5-HT2B metabolism
Fenfluramine analogs & derivatives
Heart Valve Diseases chemically induced
Hypertension, Pulmonary chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1557
- Volume :
- 23
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Pharmacoepidemiology and drug safety
- Publication Type :
- Academic Journal
- Accession number :
- 24817577
- Full Text :
- https://doi.org/10.1002/pds.3642