Thiazolidinediones, Metformin, and Outcomes in Older Patients With Diabetes and Heart Failure

Ovid Technologies (Wolters Kluwer Health) - Tập 111 Số 5 - Trang 583-590 - 2005
Frederick A. Masoudi1, Silvio E. Inzucchi1, Li Wang1, Edward P. Havranek1, JoAnne M. Foody1, Harlan M. Krumholz1
1From the Department of Medicine, Denver Health Medical Center (F.A.M., E.P.H.), and Department of Medicine, University of Colorado Health Sciences Center (F.A.M., E.P.H.), Denver, Colo; Colorado Foundation for Medical Care (F.A.M., E.P.H., H.M.K.) and Colorado Health Outcomes Program (F.A.M.), Aurora, Colo; and Department of Medicine (Y.W., S.E.I., J.M.F., H.M.K.), Yale University School of Medicine, and Center for Outcomes Research and Evaluation (H.M.K.), Yale-New Haven Hospital, New Haven, Conn.

Tóm tắt

Background— Insulin-sensitizing drugs of the thiazolidinedione class and metformin are commonly prescribed to treat diabetes in patients with heart failure despite strong warnings from the Food and Drug Administration against this practice. Whether this results in adverse outcomes is unknown. Methods and Results— We conducted a retrospective cohort study of 16 417 Medicare beneficiaries with diabetes discharged after hospitalization with the principal discharge diagnosis of heart failure. The association between antidiabetic drug prescriptions and outcomes was assessed in multivariable hierarchical Cox proportional hazards models, with adjustment for patient, physician, and hospital variables and accounting for the clustering of patients within hospitals. The primary outcome of the study was time to death due to all causes. Secondary outcomes included time to readmission for all causes or for heart failure. Crude 1-year mortality rates were lower among the 2226 patients treated with a thiazolidinedione (30.1%) or the 1861 treated with metformin (24.7%) compared with that among the 12 069 treated with neither insulin-sensitizing drug (36.0%, P =<0.0001 for both comparisons). In multivariable models, treatment with the thiazolidinediones (hazard ratio [HR] 0.87, 95% CI 0.80 to 0.94) or metformin (HR=0.87, 95% CI 0.78 to 0.97) was associated with significantly lower risks of death. There was no association with treatment with sulfonylureas (HR=0.99, 95% CI 0.91 to 1.08) or insulin (HR=0.96, 95% CI 0.88 to 1.05) and mortality. Admissions for all causes did not differ with either insulin sensitizer. There was a higher risk of readmission for heart failure with thiazolidinedione treatment (HR 1.06, 95% CI 1.00 to 1.09) and a lower risk with metformin treatment (HR 0.92, 95% CI 0.92 to 0.99). Conclusions— This observational study suggests that thiazolidinediones and metformin are not associated with increased mortality and may improve outcomes in older patients with diabetes and heart failure. Randomized trials are warranted to corroborate these findings.

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Tài liệu tham khảo

Takeda Pharmaceuticals. Actos prescribing information 2002. Available at: http://www.actos.com/pi.pdf. Accessed October 11 2004.

GlaxoSmithKline Pharmaceuticals. Avandia prescribing information 2002. Available at: http://us.gsk.com/products/assets/us_avandia.pdf. Accessed October 11 2004.

Bristol-Meyers Squibb Company. Glucophage and Glucophage XR prescribing information 2002. Available at: http://www.bms.com. Accessed October 11 2004.

US Food and Drug Administration. Summary for Actos and Avandia April 26 2002. Available at: http://www.fda.gov/medwatch/safety/2002/summary-actos-avandia.pdf. Accessed October 11 2004.

10.1161/01.cir.0000103683.99399.7e

10.1161/circ.104.24.2996

10.1001/jama.290.1.81

10.2105/AJPH.86.10.1481

American Hospital Association. The AHA Annual Survey Database: Fiscal Year 2000 Documentation. Chicago Ill: Health Forum AHA; 2001.

10.2337/diacare.17.10.1100

10.1056/NEJM199508313330902

10.2337/diacare.24.2.308

10.2337/diacare.23.11.1605

10.1001/jama.283.13.1695

10.1001/archinte.163.21.2594

10.2337/diacare.22.6.925

10.2337/diacare.26.11.2983

10.4065/78.9.1088

10.1016/S0735-1097(03)00159-1

10.2337/diab.46.3.433

10.2337/diacare.25.11.2058

10.2337/diabetes.50.5.1166

10.1136/bmj.310.6972.83

10.2337/diacare.13.1.1

10.2337/diacare.19.1.64

10.1016/S0140-6736(98)07037-8

10.2337/diacare.21.5.796

10.1161/hyp.34.1.83

10.1210/jcem.83.5.4932

10.1161/01.cir.0000025403.20953.23

10.2337/diabetes.49.4.633

Kotchen TA, Zhang HY, Reddy S, Hoffmann RG. Effect of pioglitazone on vascular reactivity in vivo and in vitro. Am J Physiol. 1996; 270: R660–R666.

10.1161/circ.101.10.1165