Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus

Abstract

Purpose To evaluate and quantify in diabetic patients treated with benfluorex in France, a fenfluramine-derivated product, a possible increase in risk of valvular heart disease, previously suggested by several published case reports. Methods This was a French comparative cohort study using data from two large national linked databases, health insurance system (SNIIRAM) and hospitalization (PMSI). Conclusions Benfluorex in diabetic patients was significantly associated with hospitalization for valvular heart disease in the 2 years following benfluorex exposure. Linkage between SNIIRAM and PMSI databases is in France a valuable tool to quantify the risk of serious adverse drug reactions.

Increased Risk of Left Heart Valve Regurgitation Associated With Benfluorex Use in Patients With Diabetes Mellitus

“…9 These series of observations were followed by retrospective cohort studies estimating of the risk of valvular damage, hospitalizations, valve surgery, and death associated with benfluorex exposure. 10,11 The first cohort study by Weill et al 10 used the database of the French National System of Reimbursement Information (Système national d'information inter régime de l'assurance maladie) and discharge diagnostic data from public and private hospitalizations (Programme de médicalisation des systèmes d'informations) and analyzed diabetic patients 40 to 69 years of age with reimbursements for antidiabetic drugs in 2006. The authors reported a 3-fold increase in the risk of hospital admission for mitral regurgitation and a 4-fold increase in the risk of hospitalization for aortic regurgitation and valvular replacement surgery during the first 2 years after exposure to benfluorex.…”

“…7 Moreover, 2 case-control studies have reported an important proportion of benfluorex use in patients admitted to hospital for severe organic mitral regurgitation of unclear origin. 8,9 In a retrospective cohort study of 2 French national databases including a large number of patients with diabetes mellitus, Weill et al 10 observed a 3-fold increase in the risk of hospitalization for valve regurgitation and a 4-fold increase in the risk of valve replacement surgery in patients exposed to benfluorex. According to recent estimations, exposure to benfluorex might have been responsible for up to 3100 admissions to hospital for valvular heart disease and up to 1300 deaths resulting from valve regurgitations in France.…”

Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France

“…16 This has been widely used to conduct large epidemiologic studies. [17][18][19][20][21][22][23] Further information regarding its organization is provided in the supplemental Appendix available on the Blood Web site. The SNIIR-AM collects prospective data on demographic and health expenditure reimbursements of the entire French population (65 586 million inhabitants in January 2013).…”

Response to the letter by Deltour et al.

“…We indeed considered that only 68% were benfluorex-attributable (etiologic fraction corresponding to the benfluorex-associated RR of hospitalization for valvular insufficiency: (3.1-1)/3.1 = 0.68). We agree with Deltour et al that several thresholds of risk could have been defined based on a time-to-event approach according to treatment exposure in de novo benfluorex users, but unfortunately, this approach had not been implemented by Weill et al 1 This lack of data on the excess risk among individuals who consumed fewer than 30 benfluorex boxes led us to ignore valvular insufficiencies caused by benfluorex in such individuals. Would we have had data according to duration of exposure, our estimates of the numbers of benfluorex-attributable hospitalizations and deaths would have certainly been larger.…”