In Reply: Dr Konstantinopoulos and colleagues raise the issue of the potential effect of concomitant aspirin use with TZDs on cardiac outcomes. We agree that aspirin use would have been an important variable to consider in our study. However, because aspirin is available without a prescription in Ontario, it is not covered by the provincial drug plan and is thus not captured by our databases.
Although the rate of cardiovascular events might be predicted to have been lower overall in patients taking aspirin,1 there is no reason to believe that aspirin treatment in our study was different between TZD and non-TZD users. First, history of cardiovascular disease (the primary indication for aspirin) was generally similar between oral hypoglycemic drug groups, and our analyses further matched and adjusted for cardiovascular variables. Second, we did consider other important medications in our study, and more than 64% of TZD-treated patients were taking at least 1 other cardioprotective agent. The use of β-adrenergic antagonists and angiotensin-converting enzyme inhibitors was evenly distributed between TZD and non-TZD users, and statin treatment was somewhat higher among TZD users (56% vs 46%). The use of nonsteroidal anti-inflammatory drugs, which like aspirin nonselectively inhibit both COX-1 and COX-2, was also similar across drug groups. Even after fully adjusting for these prescriptions, our study still found a higher risk of cardiac events among patients taking TZDs vs other oral hypoglycemic agents. We feel that it is therefore unlikely that aspirin use was a significant confounder in our findings because TZD-treated patients likely used aspirin to the same extent as patients taking other oral diabetes drugs.
Lipscombe LL, Alter DA. Effect of Aspirin Use on Thiazolidinediones and Cardiovascular Events—Reply. JAMA. 2008;299(13):1539-1540. doi:10.1001/jama.299.13.1539-b