{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:38:50Z","timestamp":1791333530416,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,5,10]],"date-time":"2014-05-10T00:00:00Z","timestamp":1399680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of its metabolites, norfenfluramine. The 5\u2010HT<jats:sub>2B<\/jats:sub> receptor, expressed on heart valves, acts as culprit receptor for drug\u2010induced 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\u2010sectional trial shows that about 7% of patients without a history of VHD previously exposed to benfluorex present echocardiographic features of drug\u2010induced 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\u2010channel blockade. Further studies should be conducted to determine the subsequent course of benfluorex\u2010induced VHD and PAH, and to identify genetic, biological and clinical factors that determine individual susceptibility to developing such adverse effects. 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