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Vildagliptin preserved protective effects of ischemic preconditioning in diabetes, CAD
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ADA 70th Scientific Sessions
ORLANDO — Compared with repaglinide, vildagliptin did not affect the protective mechanism of myocardial ischemic preconditioning in patients with type 2 diabetes and symptomatic coronary artery disease, suggesting a good alternative treatment for this population, researchers said here.
The study included 81 patients with type 2 diabetes, a positive exercise test and multivessel coronary artery disease. During phase 1 of the trial, patients underwent two consecutive treadmill exercise tests. During phase 2, patients were randomly assigned to repaglinide 2 mg (n=42) or vildagliptin 100 mg (n=38) and underwent two more consecutive tests so researchers could determine the effects of hypoglycemic drugs on myocardial ischemic preconditioning.
During phase 1, ischemic preconditioning was demonstrated by improvement in time to 1 mm of ST segment depression, according to the results.
All patients assigned to both hypoglycemic therapies developed ischemia in phase 2 of the trial. However, 83.3% of patients assigned to repaglinide (Prandin, Novo Nordisk) experienced ischemia earlier, which indicated cessation of ischemic preconditioning, according to the researchers.
Nearly three-quarters of patients assigned to vildagliptin (Galvus, Novartis) preserved the protective effect of ischemic preconditioning, and only 28% demonstrated ischemic preconditioning cessation.
The researchers hypothesized that vildagliptin eliminated myocardial ischemic preconditioning via its effect on the ATP-potassium channel.
Ischemic preconditioning is defined as short periods of myocardial ischemia that promote resistance to a subsequent ischemic insulin. It is considered a protective mechanism for myocardial necrosis. Previous research has indicated that some hypoglycemic drugs can eliminate this protective phenomenon. - by Matthew Brannon
The idea that an agent can potentially affect potassium channels of the heart modifies the normal post-ischemic response in the myocardium in humans is really a relevant issue in terms of prescribing. The sulfonylureas are becoming less popular with time and the data have been somewhat concerning related to sulfonylureas and heart disease now for 3 or 4 decades. Now this new class, the glinides, really modify insulin secretion in a different way but do it mechanistically, probably through the same ion channels, and the fact that it modifies the myocardial response to ischemia is of concern.
– Robert H. Eckel, MD
Program Director,
Adult General Clinical Research Center,
University of Colorado Health Sciences
Center
For more information:
- Rahmi R. 784-P. Presented at: The American Diabetes Association 70th Scientific Sessions; June 25-29, 2010; Orlando.
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