ABSTRACT Objective: To describe the prevalence and evaluate the risk of echocardiogram-determined valvulopathy in patients who received fenfluramine and phentermine in an effort to lose weight, in comparison with normal control subjects. Methods: A historical cohort study was conducted in a clinical obesity-management practice. A total of 164 patients (88% women) who were treated with fenflur- amine-phentermine for weight loss had echocardiographic evaluations. A subsample was cross-validated. Results: The prevalence of mild or greater aortic regurgitation was 18.3%, and the prevalence of moderate or greater mitral regurgitation was 3.7%. The prevalences of mild or greater tricuspid and pulmonary valve regurgi- tation, valve thickening, and pulmonary hypertension were 23.2%, 5.5%, 10.4%, and 6.7%, respectively. No sig- nificant increases in risk were found for moderate or greater regurgitation of any valve. Patients had at least a 3- fold risk for mild or greater aortic regurgitation (standard- ized morbidity ratio [SMR] = 3.03; 95% confidence inter- val [CI] = 2.05 to 4.33) and a 2-fold risk for tricuspid regurgitation (SMR = 2.24; 95% CI = 1.58 to 3.06) in comparison with normal healthy adults. Age and duration of drug therapy predicted increased risk for aortic regurgi- tation. Four patients who had moderate or greater aortic regurgitation had taken the fenfluramine-phentermine combination continuously for 454, 615, 645, and 984 days. Conclusion: Use of serotonergic anorexiant medica- tions may increase risk for mild or greater aortic and tri- cuspid regurgitation, although selection bias and obesity as causes of the association cannot be ruled out. Age and duration of drug therapy were predictors of aortic valvu- lopathy. Population-based studies are needed to confirm these preliminary findings. (Endocr Pract. 1999;5:17-23) INTRODUCTION As the prevalence of obesity continues to increase (1,2) despite dietary, behavioral, and exercise-based inter- ventions (3), a resurgence of interest in pharmacologic treatments has been evident (4). The popularity of the fen- fluramine and phentermine (“fen-phen”) combination led to a substantial increase in the use of fenfluramine between 1992 and 1997. The association of fenfluramine and dexfenfluramine with pulmonary hypertension had been reported in European case-control studies (5), but with an estimated absolute risk of 28.2 per million patient-years of exposure, this risk might be considered modest in comparison with the potential lives lost to obesity-related diseases (6). A report of 24 patients with cardiac valvular abnormalities who had taken anorexiant medications but had no previous history of heart problems raised additional safety concerns about anorexiant agents (7). Cases of anorexiant-associat- ed cardiac valvular disease leading to surgical intervention also have been reported (8). The Food and Drug Administration (FDA) provided information about abnormal echocardiographic findings in 92 of 291 asymptomatic patients reported by 5 clinical or research centers (9). The FDA estimated the prevalence of at least mild aortic and at least moderate mitral regurgita- tion to be 28.0% and 7.7%, respectively (9). Overall risk of any valvulopathy was estimated to be almost 15 times greater and relative risk of aortic regurgitation 23 times greater than background estimates from the CARDIA Study (9). On the basis of these data, the FDA requested voluntary withdrawal of these drugs from the market (8). More recently, Sander and colleagues (10) noted aortic regurgitation in 20% of their patients taking either fenflur- amine-phentermine or fenfluramine-mazindol. Weissman (11) reported no difference in the prevalence of clinically relevant heart valve regurgitation between patients taking dexfenfluramine for 2 to 3 months and those taking placebo. The purposes of this study were (1) to describe the prevalence of echocardiogram-determined valvulopathy ECHOCARDIOGRAPHIC ASSESSMENT OF PATIENTS RECEIVING LONG-TERM TREATMENT WITH ANOREXIANT MEDICATIONS Richard L. Bowen, M.D., 1 John P. Foreyt, Ph.D., 2 Walker S. Carlos Poston II, Ph.D., 2 Charles C. Miller III, Ph.D., 2 David Hyman, M.D., M.P.H., 2 Victor R. Pendleton, M.S., 2 Subroto Gangopadhyay, M.D., 2 C. Keith Haddock, Ph.D., 3 G. Ken Goodrick, Ph.D., 2 and Steve Lehbar, M.D., F.A.C.C. 4 Submitted for publication April 22, 1998 Accepted for publication September 25, 1998 From 1 Private Practice, Family Medicine, Naples, Florida, 2 Baylor College of Medicine, Houston, Texas, 3 University of Missouri, Kansas City, Missouri, and 4 Private Practice, Cardiology, Naples, Florida. Correspondence to Dr. W. S. C. Poston II, 6535 Fannin, MS F-700, Behavioral Medicine Research Center, Baylor College of Medicine, Houston, TX 77030. © 1999 AACE. ENDOCRINE PRACTICE Vol. 5 No. 1 January/February 1999 17 Original Article