Valvular heart disease associated with fenfluramine phentermine

Heidi M. Connolly, Jack L. Crary, Michael D. McGoon, Donald D. Hensrud, Brooks Sayre Edwards, William D. Edwards, Hartzell V Schaff

Research output: Contribution to journalArticle

1233 Citations (Scopus)

Abstract

Background Fenfluramine and phentermine have been individually approved 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 agent 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 million. Methods We identified valvular heart disease in 24 women treated with fenfluramine-phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As increasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these features and fenfluramine-phentermine therapy. Results Twenty-four women (mean [±SD] age, 44±8 years) were evaluated 12.3±7.1 months after the initiation of fenfluramine-phentermine therapy. Echocardiography demonstrated unusual valvular morphology and regurgitation in all patients. Both right- sided and left-sided heart valves were involved. Eight women also had newly documented pulmonary hypertension. To date, cardiac surgical intervention has been required in five patients. The heart valves had a glistening white appearance. Histopathological findings included plaque-like encasement of the leaflets and chordal structures with intact valve architecture. The histopathological features were identical 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 potential adverse effects, including pulmonary hypertension and valvular heart disease.

Original languageEnglish (US)
Pages (from-to)581-588
Number of pages8
JournalNew England Journal of Medicine
Volume337
Issue number9
DOIs
StatePublished - Aug 28 1997

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Phentermine
Fenfluramine
Heart Valve Diseases
Heart Valves
United States Food and Drug Administration
Pulmonary Hypertension
Ergotamine
Heart Murmurs
Appetite Depressants
Pulmonary Heart Disease
Carcinoid Tumor
Drug Combinations
Therapeutics
Prescriptions
Echocardiography
Heart Diseases

ASJC Scopus subject areas

  • Medicine(all)

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Valvular heart disease associated with fenfluramine phentermine. / Connolly, Heidi M.; Crary, Jack L.; McGoon, Michael D.; Hensrud, Donald D.; Edwards, Brooks Sayre; Edwards, William D.; Schaff, Hartzell V.

In: New England Journal of Medicine, Vol. 337, No. 9, 28.08.1997, p. 581-588.

Research output: Contribution to journalArticle

Connolly, Heidi M. ; Crary, Jack L. ; McGoon, Michael D. ; Hensrud, Donald D. ; Edwards, Brooks Sayre ; Edwards, William D. ; Schaff, Hartzell V. / Valvular heart disease associated with fenfluramine phentermine. In: New England Journal of Medicine. 1997 ; Vol. 337, No. 9. pp. 581-588.
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abstract = "Background Fenfluramine and phentermine have been individually approved 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 agent 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 million. Methods We identified valvular heart disease in 24 women treated with fenfluramine-phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As increasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these features and fenfluramine-phentermine therapy. Results Twenty-four women (mean [±SD] age, 44±8 years) were evaluated 12.3±7.1 months after the initiation of fenfluramine-phentermine therapy. Echocardiography demonstrated unusual valvular morphology and regurgitation in all patients. Both right- sided and left-sided heart valves were involved. Eight women also had newly documented pulmonary hypertension. To date, cardiac surgical intervention has been required in five patients. The heart valves had a glistening white appearance. Histopathological findings included plaque-like encasement of the leaflets and chordal structures with intact valve architecture. The histopathological features were identical 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 potential adverse effects, including pulmonary hypertension and valvular heart disease.",
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AB - Background Fenfluramine and phentermine have been individually approved 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 agent 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 million. Methods We identified valvular heart disease in 24 women treated with fenfluramine-phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As increasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these features and fenfluramine-phentermine therapy. Results Twenty-four women (mean [±SD] age, 44±8 years) were evaluated 12.3±7.1 months after the initiation of fenfluramine-phentermine therapy. Echocardiography demonstrated unusual valvular morphology and regurgitation in all patients. Both right- sided and left-sided heart valves were involved. Eight women also had newly documented pulmonary hypertension. To date, cardiac surgical intervention has been required in five patients. The heart valves had a glistening white appearance. Histopathological findings included plaque-like encasement of the leaflets and chordal structures with intact valve architecture. The histopathological features were identical 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 potential adverse effects, including pulmonary hypertension and valvular heart disease.

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