Clinical and echocardiographic follow-up of patients previously treated with dexfenfluramine or phentermine/fenfluramine

Context Use of anorexigen therapy is associated with valvular abnormalities, although there is limited information on long-term changes in valvular regurgitation following discontinuation of these agents. Objective To evaluate changes in valvular regurgitation, valve morphology, and clinical parameters 1 year after an initial echocardiogram in patients previously treated with dexfenfluramine or phentermine/fenfluramine and in untreated controls. Design and Setting A reader-blinded, multicenter, echocardiographic and clinical 1-year follow-up study at 25 outpatient clinical sites. Patients A total of 1142 obese patients (1466 participated in the initial study) who had follow-up echocardiogram; all but 4 had a follow-up medical history and physical examination. Follow-up time from discontinuation of drug to follow-up echocardiogram for 371 dexfenfluramine patients was 17.5 months (range, 13-26 months) and for 340 phentermine/fenfluramine patients was 18.7 months (range, 13-26 months) after discontinuation of drug therapy. Main Outcome Measure Change in grade of valvular regurgitation and valve morphology and mobility. Results Echocardiographic changes in aortic regurgitation were observed in 8 controls (7 [1.7%] had decreases; 1 [0.2%]had an increase); 29 dexfenfluramine patients (23 [6.4%] had decreases; 6 [1.7%] had increases; P<.001 vs controls); and 15 phentermine/fenfluramine patients (4.5% all decreases; P=.03 vs controls). No statistically significant differences were observed when treated patients were compared with controls for changes in medical history, physical findings, mitral regurgitation, aortic or mitral leaflet mobility or thickness, pulmonary artery systolic pressure, ejection fraction, valve surgery, or cardiovascular events. Conclusion Progression of valvular abnormalities is unlikely in patients 1 year after an initial echocardiogram and 13 to 26 months after discontinuation of dexfenfluramine and phentermine/fenfluramine.