Rosiglitazone and outcomes for patients with diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial

Abstract

Background: Rosiglitazone improves glycemic control for patients with type 2 diabetes mellitus, but there remains controversy regarding an observed association with cardiovascular hazard. The cardiovascular effects of rosiglitazone for patients with coronary artery disease remain unknown.

Methods and results: To examine any association between rosiglitazone use and cardiovascular events among patients with diabetes mellitus and coronary artery disease, we analyzed events among 2368 patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Total mortality, composite death, myocardial infarction, and stroke, and the individual incidence of death, myocardial infarction, stroke, congestive heart failure, and fractures, were compared during 4.5 years of follow-up among patients treated with rosiglitazone versus patients not receiving a thiazolidinedione by use of Cox proportional hazards and Kaplan-Meier analyses that included propensity matching. After multivariable adjustment, among patients treated with rosiglitazone, mortality was similar (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.58-1.18), whereas there was a lower incidence of composite death, myocardial infarction, and stroke (HR, 0.72; 95% CI, 0.55-0.93) and stroke (HR, 0.36; 95% CI, 0.16-0.86) and a higher incidence of fractures (HR, 1.62; 95% CI, 1.05-2.51); the incidence of myocardial infarction (HR, 0.77; 95% CI, 0.54-1.10) and congestive heart failure (HR, 1.22; 95% CI, 0.84-1.82) did not differ significantly. Among propensity-matched patients, rates of major ischemic cardiovascular events and congestive heart failure were not significantly different.

Conclusions: Among patients with type 2 diabetes mellitus and coronary artery disease in the BARI 2D trial, neither on-treatment nor propensity-matched analysis supported an association of rosiglitazone treatment with an increase in major ischemic cardiovascular events.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Keywords: coronary disease; diabetes mellitus; myocardial infarction; pharmaceutical preparations; rosiglitazone; thiazolidinediones.

Figures

Figure 1

Relative risk of adverse cardiovascular outcomes for patients on treatment with rosiglitazone compared with patients not treated with a thiazolidinedione, after adjustment for baseline characteristics and other diabetes-related medications.

Figure 2

Kaplan-Meier curves during BARI 2D follow-up comparing the incidence of events among propensity-matched patients in the insulin-provision arm who did not start the study with any thiazolidinedione (Did not start with TZD) vs. similar patients in the insulin-sensitization arm who started the study with rosiglitazone (Started with RSG) of (A) all cause death; (B) the composite of death, MI, and stroke; (C) MI (excluding procedure-related MI); (D) stroke; (E) CHF; and (F) fractures. Numbers of patients at risk at baseline, 2 years, and 4 years are shown below each graph.

Figure 2

Kaplan-Meier curves during BARI 2D follow-up comparing the incidence of events among propensity-matched patients in the insulin-provision arm who did not start the study with any thiazolidinedione (Did not start with TZD) vs. similar patients in the insulin-sensitization arm who started the study with rosiglitazone (Started with RSG) of (A) all cause death; (B) the composite of death, MI, and stroke; (C) MI (excluding procedure-related MI); (D) stroke; (E) CHF; and (F) fractures. Numbers of patients at risk at baseline, 2 years, and 4 years are shown below each graph.

Figure 2

Kaplan-Meier curves during BARI 2D follow-up comparing the incidence of events among propensity-matched patients in the insulin-provision arm who did not start the study with any thiazolidinedione (Did not start with TZD) vs. similar patients in the insulin-sensitization arm who started the study with rosiglitazone (Started with RSG) of (A) all cause death; (B) the composite of death, MI, and stroke; (C) MI (excluding procedure-related MI); (D) stroke; (E) CHF; and (F) fractures. Numbers of patients at risk at baseline, 2 years, and 4 years are shown below each graph.

Figure 2

Kaplan-Meier curves during BARI 2D follow-up comparing the incidence of events among propensity-matched patients in the insulin-provision arm who did not start the study with any thiazolidinedione (Did not start with TZD) vs. similar patients in the insulin-sensitization arm who started the study with rosiglitazone (Started with RSG) of (A) all cause death; (B) the composite of death, MI, and stroke; (C) MI (excluding procedure-related MI); (D) stroke; (E) CHF; and (F) fractures. Numbers of patients at risk at baseline, 2 years, and 4 years are shown below each graph.

Figure 2

Kaplan-Meier curves during BARI 2D follow-up comparing the incidence of events among propensity-matched patients in the insulin-provision arm who did not start the study with any thiazolidinedione (Did not start with TZD) vs. similar patients in the insulin-sensitization arm who started the study with rosiglitazone (Started with RSG) of (A) all cause death; (B) the composite of death, MI, and stroke; (C) MI (excluding procedure-related MI); (D) stroke; (E) CHF; and (F) fractures. Numbers of patients at risk at baseline, 2 years, and 4 years are shown below each graph.

Figure 2

Kaplan-Meier curves during BARI 2D follow-up comparing the incidence of events among propensity-matched patients in the insulin-provision arm who did not start the study with any thiazolidinedione (Did not start with TZD) vs. similar patients in the insulin-sensitization arm who started the study with rosiglitazone (Started with RSG) of (A) all cause death; (B) the composite of death, MI, and stroke; (C) MI (excluding procedure-related MI); (D) stroke; (E) CHF; and (F) fractures. Numbers of patients at risk at baseline, 2 years, and 4 years are shown below each graph.