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Thiazolidinediones and Cardiovascular Outcomes in Older Patients With Diabetes
Lorraine L. Lipscombe, MD, MSc;
Tara Gomes, MHSc;
Linda E. Lévesque, BScPhm, MSc;
Janet E. Hux, MD, MSc;
David N. Juurlink, BPhm, MD, PhD;
David A. Alter, MD, PhD
JAMA. 2007;298(22):2634-2643.
Context 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.
Objective To explore the association between TZD therapy and congestive heart failure, acute myocardial infarction, and mortality compared with treatment with other oral hypoglycemic agents.
Design, Setting, and Patients Nested case-control analysis of a retrospective cohort study using health care databases in Ontario. We included diabetes patients aged 66 years or older treated with at least 1 oral hypoglycemic agent between 2002 and 2005 (N = 159 026) and followed them up until March 31, 2006.
Main Outcome Measures 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.
Results 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 (3478 congestive heart failure cases, 3695 acute myocardial infarction cases, and 5529 deaths). The increased risk of congestive heart failure, acute myocardial infarction, and mortality associated with TZD use appeared limited to rosiglitazone.
Conclusion 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 with other combination oral hypoglycemic agent treatments.
Author Affiliations: Institute for Clinical Evaluative Sciences (Drs Lipscombe, Hux, Juurlink, and Alter and Mss Gomes and Lévesque), Departments of Medicine (Drs Lipscombe, Hux, Juurlink, and Alter) and Health Policy, Management and Evaluation (Drs Hux, Juurlink, and Alter), University of Toronto, Women's College Hospital (Dr Lipscombe), Sunnybrook Health Sciences Centre (Drs Hux and Juurlink), Li Ka Shing Knowledge Institute of St Michael’s Hospital (Dr Alter), and Toronto Rehabilitation Institute (Dr Alter), Toronto, Ontario; Department of Community Health and Epidemiology, Queen's University (Ms Lévesque), and Kingston, Lennox, Frontenac and Addington Public Health (Dr Lévesque), Kingston, Ontario.
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