Insulin-Sensitizing Antihyperglycemic Drugs and Mortality After Acute Myocardial Infarction
Insights from the National Heart Care Project
- Silvio E. Inzucchi, MD1,
- Frederick A. Masoudi, MD, MSPH2345,
- Yongfei Wang, MS6,
- Mikhail Kosiborod, MD6,
- Joanne M. Foody, MD6,
- John F. Setaro, MD6,
- Edward P. Havranek, MD25 and
- Harlan M. Krumholz, MD5678
- 1Section of Endocrinology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
- 2Division of Cardiology, Department of Medicine, Denver Health Medical Center, Denver, Colorado
- 3Division of Geriatric Medicine, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado
- 4Colorado Health Outcomes Program, Aurora, Colorado
- 5Colorado Foundation for Medical Care, Aurora, Colorado
- 6Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
- 7Section of Health Policy and Administration, School of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut
- 8Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut
- Address correspondence and reprint requests to Silvio E. Inzucchi, MD, Section of Endocrinology, Yale University School of Medicine, 333 Cedar St./LLCI-101, New Haven, CT 06520-8020. E-mail: silvio.inzucchi{at}yale.edu
Abstract
OBJECTIVE—Thiazolidinediones (TZDs) and metformin are insulin-sensitizing antihyperglycemic agents with reported benefits on atherosclerosis. Despite extensive use in patients with diabetes and cardiovascular disease, there is a paucity of outcomes data with metformin and none yet with TZDs. We sought to determine the impact of these insulin sensitizers on outcomes in diabetic patients after hospitalization with acute myocardial infarction (AMI).
RESEARCH DESIGN AND METHODS—We conducted a retrospective cohort study of 24,953 Medicare beneficiaries with diabetes discharged after hospitalization with AMI between April 1998 and March 1999 or July 2000 and June 2001. The independent association between discharge prescription for metformin, TZD, or both agents and outcomes at 1 year was assessed in multivariable Cox proportional hazards models, adjusting for patient, physician, and hospital variables. The primary outcome was time to death within 1 year of discharge; secondary outcomes were time to first rehospitalization within 1 year of discharge for AMI, heart failure, and all causes.
RESULTS—There were 8,872 patients discharged on an antihyperglycemic agent, of which 819 were prescribed a TZD, 1,273 metformin, and 139 both drugs. After multivariable analysis, compared with patients prescribed an antihyperglycemic regimen that included no insulin sensitizer, mortality rates were not significantly different in patients treated with either metformin (hazard ratio [HR] 0.92 [95% CI 0.81–1.06]) or a TZD (0.92 [0.80–1.05]) but were lower in those prescribed both drugs (0.52 [0.34–0.82]). The results were similar among patients with heart failure. The prescription of a TZD was associated with a borderline higher risk of all-cause readmission (1.09[1.00–1.20]), predominately due to a higher risk for heart failure readmission (1.17 [1.05–1.30]).
CONCLUSIONS—Individually, prescription of insulin-sensitizing drugs is not associated with a significantly different risk of death in older diabetic patients within 1 year following AMI compared with other antihyperglycemic agents. Combined, however, metformin and TZDs may exert benefit. TZD prescription is associated with a higher risk of readmission for heart failure after myocardial infarction.
Footnotes
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S.E.I. has served on an advisory board for Takeda and has received honoraria from Takeda and Glaxo-Smith Kline. F.A.M. has served on an advisory board for Takeda and has received honoraria from Pfizer and AstraZeneca. E.P.H. has received honorarium from Takeda.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted April 10, 2005.
- Received December 11, 2004.
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