VALVULAR HEART-DISEASE ASSOCIATED WITH FENFLURAMINE-PHENTERMINE

Background Fenfluramine and phentermine have been individually approve d as anorectic agents by the Food and Drug Administration (FDA). When used in combination the drugs may be just as effective as either drug alone, with the added advantages of the need for lower doses of each a gent and perhaps fewer side effects. Although the combination has not been approved by the FDA, in 1996 the total number of prescriptions in the United States for fenfluramine and phentermine exceeded 18 millio n. Methods We identified valvular heart disease in 24 women treated wi th fenfluramine-phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As in creasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these feature s and fenfluramine-phentermine therapy. Results Twenty-four women (mea n [+/-SD] age, 44+/-8 years) were evaluated 12.3+/-7.1 months after th e initiation of fenfluramine-phentermine therapy. Echocardiography dem onstrated unusual valvular morphology and regurgitation in all patient s. Both right-sided and left-sided heart valves were involved. Eight w omen also had newly documented pulmonary hypertension. To date, cardia c surgical intervention has been required in five patients. The heart valves had a glistening white appearance. Histopathological findings i ncluded plaque-like encasement of the leaflets and chordal structures with intact valve architecture. The histopathological features were id entical to those seen in carcinoid or ergotamine-induced valve disease . Conclusions These cases arouse concern that fenfluramine-phentermine therapy may be associated with valvular heart disease. Candidates for fenfluramine-phentermine therapy should be informed about serious pot ential adverse effects, including pulmonary hypertension and valvular heart disease. (C) 1997, Massachusetts Medical Society.