Fenfluramine and phentermine and cardiovascular findings - Effect of treatment duration on prevalence of valve abnormalities

Background-The combination of fenfluramine and phentermine was a widely use d obesity treatment before the withdrawal of fenfluramine for an associatio n with heart valve regurgitation. The prevalence and clinical significance of regurgitation among patients treated with these medications has yet to b e fully established. Methods and Results-To evaluate the potential association between the durat ion of treatment and the prevalence of heart valve abnormalities, we examin ed 1163 patients who had taken fenfluramine-phentermine and 672 control pat ients who had not taken the drug combination within 5 years. Mild or greate r 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 pr esent in 2.6% of treated patients and 1.5% of control patients (P=0.18). Th e adjusted odds ratio compared with controls of aortic regurgitation of mil d or greater severity increased according to duration of treatment: 90 to 1 80 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 va lvular 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 ao rtic regurgitation. The valve regurgitation identified by this study was no t accompanied by significant differences in cardiovascular symptoms nor phy sical findings other than a higher prevalence of heart murmurs.