Thiazolidinediones and Cardiovascular Outcomes in Older Patients With Diabetes

Abstract

ARDIOVASCULAR DISEASE IS AN important cause of morbidity and mortality among persons with type 2 diabetes mellitus. 1-3 The thiazolidinediones (TZDs), rosiglitazone and pioglitazone, are oral hypoglycemic agents that have been shown to improve glycemic control and may act to slow the progression of beta cell failure. 4 While improved glycemic control has been linked to better clinical outcomes in diabetes 5-7 and TZDs have been suggested as having potential cardiovascular benefits, 8-11 recent concerns have arisen regarding adverse cardiac effects of these drugs. Use of TZDs is associated with weight gain and edema, 12 and evidence suggests that both rosiglitazone and pioglitazone increase the risk of congestive heart failure (CHF). 8,10,13-19 A recent boxed warning for CHF was added for these agents recommending against the use of TZDs in persons with preexisting CHF. 20 Two meta-analyses have also suggested that rosiglitazone may be associated with an increased risk of acute myocardial infarction (AMI) and death. 18,21 These findings prompted a hearing by a US Food and Drug Administration advisory panel regarding the safety of rosiglitazone; however, the panel voted against removing rosiglitazone from the market because of insufficient data. 22 Most studies to date far have examined adverse cardiovascular outcomes associated with TZDs among clinical trial samples. However, the extent to which these adverse effects apply to real-world populations is less clear. In addition, older persons are traditionally underrepresented in clinical

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