Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus
Version of Record online: 13 OCT 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Pharmacoepidemiology and Drug Safety
Volume 19, Issue 12, pages 1256–1262, December 2010
How to Cite
Weill, A., Païta, M., Tuppin, P., Fagot, J.-P., Neumann, A., Simon, D., Ricordeau, P., Montastruc, J.-L. and Allemand, H. (2010), Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus. Pharmacoepidem. Drug Safe., 19: 1256–1262. doi: 10.1002/pds.2044
- Issue online: 24 NOV 2010
- Version of Record online: 13 OCT 2010
- Manuscript Accepted: 4 AUG 2010
- Manuscript Revised: 25 JUN 2010
- Manuscript Received: 14 APR 2010
- valvular heart disease;
- adverse effects;
- health insurance system;
- reimbursement databases;
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.
This was a French comparative cohort study using data from two large national linked databases, health insurance system (SNIIRAM) and hospitalization (PMSI). Patients aged 40–69 years with reimbursement for oral antidiabetic and/or insulin in 2006 were eligible. Exposed patients were defined as patients with at least one benfluorex reimbursement in 2006. Selected admission diagnoses of interest in 2007 and 2008 PMSI databases were valvular insufficiency for any cause, mitral insufficiency, aortic insufficiency, and valvular replacement surgery with cardiopulmonary bypass. Relative risks (RR) were adjusted on gender, age, and history of chronic cardiovascular disease.
A total of 1 048 173 diabetic patients were included, with 43 044 (4.1%) exposed to benfluorex. The risk of hospitalization in 2007 and 2008 for any cardiac valvular insufficiency was higher in the benfluorex group: crude RR = 2.9 [95% confidence interval 2.2–3.7] and adjusted RR = 3.1 [2.4–4.0], with a lower risk for patients with lower cumulative dose of benfluorex. Adjusted RR for mitral insufficiency and aortic insufficiency admissions were 2.5 [1.9–3.7] and 4.4 [3.0–6.6], respectively. Adjusted RR for valvular replacement surgery was 3.9 [2.6–6.1].
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. Copyright © 2010 John Wiley & Sons, Ltd.