Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy

OBJECTIVE: To determine whether the severity of valvulopathy was associated with the dosage of fenfluramine taken by fenfluramine-phentermine users wi th valvulopathy, DESIGN: Out of 105 suspected valvulopathy case reports received by the US F ood and Drug Administration (FDA) among fenfluramine-phentermine users, 74 patients meeting FDA case definition for valvulopathy were included in this study. Patients with severe valvulopathy were classified as those either u ndergoing valve replacement surgery or having severe aortic or mitral regur gitation; all other patients were considered to have less severe valvulopat hy. RESULTS: The proportion with severe valvulopathy increased from 20-66% with increasing fenfluramine dosage from less than or equal to 40 mg/d to great er than or equal to 60 mg/d, Compared with patients taking <40 mg/d fenflur amine, patients taking greater than or equal to 60 mg/d had an adjusted odd s ratio of 9.2 (95% confidence interval = 2.1-40.8) for severe valvulopathy , CONCLUSION: Compared to patients with less severe valvulopathy, those with severe valvulopathy were substantially more likely to have taken greater th an or equal to 60 mg/d fenfluramine.