Benfluorex, a drug related to fenfluramine, has been sold under the trade name “Mediator” by Servier Laboratories and was introduced to the French market in 1976, licenced for the treatment of type 2 diabetes and dyslipidemia. Although the evidence that benfluorex increases the risk of mild valvular regurgitant abnormalities is convincing, it is also apparent that no data exist from which to calculate the risk of death attributable to benfluorex use. Despite this, two studies have attempted to make such estimates, the results of which have been the focus of much media attention. In this review, we attempt to provide a further assessment of the evidence base, explore the limitations of the estimates of death that have been made, and calculate the population risk of mild valvular regurgitation and hospitalisation attributable to benfluorex use. We conclude that the previously published estimates of deaths attributed to the use of this agent are unsafe, based on unfounded assumptions, and are highly likely to be inaccurate. 1. Introduction In 2011 a media storm occurred as a result of claims that benfluorex, a Servier-manufactured drug used to treat type 2 diabetes and dyslipidemia, was responsible for “between 500 and 2000 deaths” since its introduction in 1976 [1]. We were intrigued by how readily the figures were accepted by both lay and scientific communities with little detailed examination of how they had been derived. We therefore aimed to investigate for ourselves the validity of these estimates of deaths attributable to benfluorex use. 2. Epidemiology and Assessment of Valvular Heart Disease It is helpful to briefly outline the known epidemiology and assessment of heart valve lesions to provide a context for the following discussions. The Euro Heart Survey reported findings on 5001 men and women aged 19 to 101 years recruited across 25 European countries after assessment for valvular heart disease [2]. In this study, of those with native heart valves, 33.9% had aortic stenosis, 24.8% mitral regurgitation, 10.4% aortic regurgitation, and 9.5% mitral stenosis. 20.2% had multiple lesions and 1.2% had involvement of right-sided valves. Of those with aortic stenosis, degeneration was the cause in 81.9%; the figure for aortic regurgitation was 50.3%. Mitral regurgitation in native valves was found to be degenerative in 61.3%; in contrast 85.4% of cases of mitral stenosis (MS) were found to be of rheumatic origin. Thus valvular heart disease is common in the general population. The majority of cases are mild; indeed, in an American study [3], the
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