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(Circulation. 2000;101:2071.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Fenfluramine and Phentermine and Cardiovascular Findings

Effect of Treatment Duration on Prevalence of Valve Abnormalities

Presented at the 48th Annual Scientific Session of the American College of Cardiology, New Orleans, La, March 9, 1999.

James G. Jollis, MD; Carolyn K. Landolfo, MD; Joseph Kisslo, MD; Ginger D. Constantine, MD; Kelly D. Davis, MD; Thomas Ryan, MD

From the Division of Cardiology (J.G.J., C.K.L., J.K., T.R.), Duke University Medical Center, Durham, NC, and Wyeth-Ayerst Research (G.D.C., K.D.D.), Philadelphia, Pa.

Correspondence to James G. Jollis, MD, Box 3542, Duke University Medical Center, Durham, NC 27710. E-mail james.jollis{at}duke.edu

Background—The combination of fenfluramine and phentermine was a widely used obesity treatment before the withdrawal of fenfluramine for an association with heart valve regurgitation. The prevalence and clinical significance of regurgitation among patients treated with these medications has yet to be fully established.

Methods and Results—To evaluate the potential association between the duration of treatment and the prevalence of heart valve abnormalities, we examined 1163 patients who had taken fenfluramine-phentermine and 672 control patients who had not taken the drug combination within 5 years. Mild or greater aortic regurgitation was present in 8.8% of treated patients and 3.6% of control patients (P<0.001). Moderate or greater mitral regurgitation was present in 2.6% of treated patients and 1.5% of control patients (P=0.18). The adjusted odds ratio compared with controls of aortic regurgitation of mild or greater severity increased according to duration of treatment: 90 to 180 days, 1.5 (P=0.23); 181 to 360 days, 2.4 (P=0.002); 361 to 720 days, 4.6 (P<0.001); >720 days, 6.2 (P<0.001).

Conclusions—This is the largest study to demonstrate a relation between the length of treatment with fenfluramine-phentermine and the prevalence of valvular abnormalities. These findings suggest that valvular abnormalities in patients who took fenfluramine-phentermine primarily involve those who had taken these medications for >6 months and predominantly results in mild aortic regurgitation. The valve regurgitation identified by this study was not accompanied by significant differences in cardiovascular symptoms nor physical findings other than a higher prevalence of heart murmurs.

Key Words: echocardiography • regurgitation • valves • epidemiology

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