Increased Risk of Left Heart Valve Regurgitation Associated with Benfluorex Use in Patients with Diabetes Mellitus: A Multicenter Study
Background—Benfluorex was withdrawn from European markets in June 2010 following reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least three months and in diabetic controls never exposed to the drug.
Methods and Results—This reader-blinded controlled study conducted in ten centers in France included prospectively between February 2010 and September 2011 376 diabetic subjects previously exposed to benfluorex referred by primary care physicians for echocardiography and 376 diabetic controls. Using propensity scores, 293 patients and 293 controls were matched for age, gender, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (OR) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared to controls: 31.0% vs. 12.9% (OR 3.55[2.03-6.21]) for aortic and/or mitral regurgitation; 19.8% vs. 4.7% (OR 5.29[2.46-11.4]) for aortic regurgitation; and 19.4% vs. 9.6% (OR 2.38[1.27-4.45]) for mitral regurgitation.
Conclusions—Our results indicate that use of benfluorex is associated with significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.
- Received April 9, 2012.
- Accepted October 22, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited