The Prevalence of Cardiac Valvular Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetite-Suppressant Drugs
Mehmood A. Khan, M.D., Charles A. Herzog, M.D., John V. St. Peter, Pharm.D., Guilford G. Hartley, M.D., Richard Madlon-Kay, M.D., Candace D. Dick, M.D., Richard W. Asinger, M.D., and John T. Vessey, Ph.D.
Background After case reports of cardiac-valve abnormalitiesrelated to the use of appetite suppressants were published,we undertook a study to determine the prevalence of the problemusing transthoracic echocardiography.
Methods We examined patients who had taken dexfenfluramine alone,dexfenfluramine and phentermine, or fenfluramine and phenterminefor various periods. We enrolled obese patients who had takenor were taking these agents during open-label trials from January1994 through August 1997. We also recruited subjects who hadnot taken appetite suppressants and who were matched to thepatients for sex, height, and pretreatment age and body-massindex. The presence of cardiac-valve abnormalities, definedby the Food and Drug Administration and Centers for DiseaseControl and Prevention as at least mild aortic-valve or moderatemitral-valve insufficiency, was determined independently byat least two cardiologists. Multivariate logistic-regressionanalysis was used to identify factors associated with cardiac-valveabnormalities.
Results Echocardiograms were available for 257 patients and239 control subjects. The association between the use of anyappetite suppressant and cardiac-valve abnormalities was analyzedin a final matched group of 233 pairs of patients and controls.A total of 1.3 percent of the controls (3 of 233) and 22.7 percentof the patients (53 of 233) met the case definition for cardiac-valveabnormalities (odds ratio, 22.6; 95 percent confidence interval,7.1 to 114.2; P<0.001). The odds ratio for such cardiac-valveabnormalities was 12.7 (95 percent confidence interval, 2.9to 56.4) with the use of dexfenfluramine alone, 24.5 (5.9 to102.2) with the use of dexfenfluramine and phentermine, and26.3 (7.9 to 87.1) with the use of fenfluramine and phentermine.
Conclusions Obese patients who took fenfluramine and phentermine,dexfenfluramine alone, or dexfenfluramine and phentermine hada significantly higher prevalence of cardiac valvular insufficiencythan a matched group of control subjects.
Source Information
From the Divisions of Endocrinology (M.A.K., J.V.S.), Cardiology (C.A.H., R.W.A.), and Internal Medicine (G.G.H.), Department of Medicine, Hennepin County Medical Center; Health System Minnesota (R.M.-K.); Minnesota Heart Clinic (C.D.D.); the Division of Epidemiology, School of Public Health, University of Minnesota (J.T.V.); and the Minnesota Obesity Center (M.A.K., J.V.S., G.G.H., J.T.V.) — all in Minneapolis.
Address reprint requests to Dr. Khan at the Division of Endocrinology, 701 Park Ave., 865B, Minneapolis, MN 55415.
Appetite-Suppressant Drugs and Valvular Heart Disease
Williamson D. F., Yanovski S. Z., Myers M. D., Moye L. A., Annegers J. F., Paoletti C. F., Shapiro S., Khan M. A., St. Peter J. V., Herzog C. A., Jick H., Weissman N. J., Gottdiener J. S., Gwynne J. T., Devereux R. B., Cannistra L. B., Cannistra A. J.
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N Engl J Med 1999;
340:476-480, Feb 11, 1999.
Correspondence
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