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(Circulation. 1998;97:1427-1428.)
© 1998 American Heart Association, Inc.

Correspondence

Sulfonylureas and Cardiovascular Mortality in Diabetes: A Class Effect?

Thomas C. Wascher, MD

Department of Internal Medicine, Diabetes and Metabolism Unit, University of Graz, Graz, Austria

To the Editor:

In a recent issue of Circulation, Cleveland and coworkers¹ provided excellent evidence that in diabetic patients, chronic inhibition of the K_ATP channel with oral sulfonylureas abolishes ischemic preconditioning of explanted myocardium. The authors conclude that this phenomenon might contribute to the increased cardiovascular mortality in sulfonylurea-treated diabetic patients, as found in the University Group Diabetes Programme (UGDP).² This extension of their findings in mainly glibenclamide-treated patients (6 and 1 glipizide) to sulfonylureas as a class, however, must be seen with some limitations because neither experimental nor clinical data suggest a uniform effect of different sulfonylureas on the cardiovascular system.

In experimental animals, inhibition of the cardiac K_ATP channel with glibenclamide has been shown to increase ischemia-reperfusion damage,³ whereas gliclazide, a sulfonylurea with pronounced in vivo antioxidative properties,⁴ prevented such damage.⁵

In studies in the human forearm, significant interaction with the vascular K_ATP channel was found for glibenclamide, whereas the effect was much less pronounced for tolbutamide⁶ and even absent for the new drug glimepiride.⁷

For tolbutamide (the sulfonylurea used in the UGDP), further evidence of an increased cardiovascular morbidity in comparison to glibenclamide or gliclazide was recently reported,⁸ and a possible substance-specific cardiotoxicity was suggested. Tolbutamide, as a first-generation sulfonylurea, is used in the highest dose (up to 3000 mg) of all currently available sulfonylureas (for review, see Reference 9). In a recent survey from Australia, neither glibenclamide- nor gliclazide-treated patients with myocardial infarction had higher mortality rates than insulin-treated diabetic patients.¹⁰ In the same survey, . . . [Full Text of this Article]

Joseph C. Cleveland, Jr, MD; Daniel R. Meldrum, MD; Brian S. Cain, MD; Anirban Banerjee, PhD; ; Alden H. Harken, MD

University of Colorado Health Sciences Center, Department of Surgery, Denver, Colo