Prevalence and Determinants of Valvulopathy in Patients Treated With Dexfenfluramine

Abstract

Background —Valve regurgitation has been associated with dexfenfluramine, but its prevalence and severity are uncertain. Additional factors that may contribute to valve regurgitation in patients exposed to this drug are poorly understood. Methods and Results —Echocardiography was performed on subjects recruited from 26 prescribing sites in 15 states. The total sample of 412 subjects included 172 dexfenfluramine patients and 172 unexposed controls matched for age, sex, and body mass index and 68 unmatched subjects meeting the same entry criteria (51 dexfenfluramine patients and 17 controls). Mean treatment duration was 6.9 months; mean interval from treatment discontinuation to echocardiogram was 8.5 months. Each echocardiogram was interpreted independently by 3 echocardiographers. FDA-grade regurgitation (at least mild aortic regurgitation or at least moderate mitral regurgitation) was significantly more frequent in dexfenfluramine patients (7.6% versus 2.1% for controls; P =0.01; odds ratio, 3.82). This difference was primarily due to more frequent mild aortic regurgitation in dexfenfluramine patients (6.3% versus 1.6% in controls; P <0.02; odds ratio, 4.15). No differences were found in sclerosis or mobility for either the aortic or mitral valve. Factors independently related to FDA-grade regurgitation or any grade of aortic regurgitation were older age, higher diastolic blood pressure at the time of echocardiography, and shorter time from drug discontinuation to echocardiogram. Conclusions —Dexfenfluramine use is associated with an increase in the prevalence of abnormal valve regurgitation. Age and blood pressure may also affect the prevalence of regurgitation. Dexfenfluramine-related valve regurgitation may regress after drug discontinuation.