Valvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individuals

The prevalence of at least mild aortic regurgitation (AR) or moderate mitral regurgitation (MR) was 19.6% in women and 11.8% in men (p < 0.0001 for gender difference). Duration of use was strongly predictive of mild or greater AR (p < 0.0001 for trend), MR (p = 0.002), and tricuspid regurgitation (TR) (p < 0.0001), as was earlier scan date (p < 0.0001 for those scanned prior to 1 January 2000 versus later). Increasing age was also independently associated with increased risk of AR and MR (both p < 0.0001). With mean follow-up of 30.3 months, AR worsened in 15.2%, remained the same in 63.1%, and improved in 21.7%. Corresponding values for MR were 24.8%, 47.4% and 27.9%. Pulmonary hypertension was strongly associated with MR but not AR. Valve surgery was performed on 38 patients (0.66% of 5743), 25 (0.44%) with clear evidence of fenfluramine-related etiology.Regurgitant valvulopathy was common in individuals exposed to fenfluramines, more frequent in females, and associated with duration of use in all valves assessed. Valve surgery was performed as frequently for aortic as mitral valves and some tricuspid valve surgeries were also performed. The incidence of surgery appeared to be substantially increased compared with limited general population data.An association between valvular heart disease and the anorexic drugs fenfluramine and dexfenfluramine has been reported since the summer of 1997 [1,2] and is now widely accepted [3-6]. Nevertheless, the natural history of valvular regurgitation in former users of fenfluramines has yet to be determined. Furthermore, relatively small sample sizes have limited important subgroup analyses including comparisons between men versus women and different age categories. In addition, controversy remains regarding the effect of duration of exposure for mitral regurgitation (MR) and tricuspid regurgitation (TR), while for aortic regurgitation (AR) this relationship appears strong [6-9]. Potential progression or regression of valvular r