Thiazolidinediones (TZDs), used to treat type 2 diabetes, are associated with an excess risk of congestive heart failure and possibly acute myocardial infarction. However, the association between TZD use and cardiovascular events has not been adequately evaluated on a population level.
The objective of this study was to explore the association between TZD therapy and congestive heart failure, acute myocardial infarction, and mortality compared with treatment with other oral hypoglycemic agents.
It was a nested case-control analysis of a retrospective cohort study using health care databases in Ontario, Canada. The authors included diabetes patients aged 66 years or older treated with at least one oral hypoglycemic agent between 2002 and 2005 (N=159,026) and followed them up until March 31, 2006.
The primary outcome consisted of an emergency department visit or hospitalization for congestive heart failure; secondary outcomes were an emergency department visit or hospitalization for acute myocardial infarction and all-cause mortality. The risks of these events were compared between persons treated with TZDs (rosiglitazone and pioglitazone) and other oral hypoglycemic agent combinations, after matching and adjusting for prognostic factors.
During a median follow-up of 3.8 years, 12,491 patients (7.9%) had a hospital visit for congestive heart failure, 12,578 (7.9%) had a visit for acute myocardial infarction, and 30,265 (19%) died. Current treatment with TZD monotherapy was associated with a significantly increased risk of congestive heart failure (78 cases; adjusted rate ratio [RR], 1.60; 95% confidence interval [CI], 1.21-2.10; P<.001), acute myocardial infarction (65 cases; RR, 1.40; 95% CI, 1.05-1.86; P=.02), and death (102 cases; RR, 1.29; 95% CI, 1.02-1.62; P=.03) compared with other oral hypoglycemic agent combination therapies (3,478 congestive heart failure cases, 3,695 acute myocardial infarction cases, and 5,529 deaths). The increased risk of congestive heart failure, acute myocardial infarction, and mortality associated with TZD use appeared limited to rosiglitazone.
In this population-based study of older patients with diabetes, TZD treatment, primarily with rosiglitazone, was associated with an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared to other combination oral hypoglycemic agent treatments.