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

Randomized Controlled Trial

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

Richard G Bach et al. Circulation. 2013.

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.

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Figures

Figure 1

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

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

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

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

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

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

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.

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References

    1. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O’Neill MC, Zinman B, Viberti G. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–2443. - PubMed
    1. Kelly AS, Thelen AM, Kaiser DR, Gonzalez-Campoy JM, Bank AJ. Rosiglitazone improves endothelial function and inflammation but not asymmetric dimethylarginine or oxidative stress in patients with type 2 diabetes mellitus. Vasc Med. 2007;12:311–318. - PubMed
    1. Esposito K, Ciotola M, Carleo D, Schisano B, Saccomanno F, Sasso FC, Cozzolino D, Assaloni R, Merante D, Ceriello A, Giugliano D. Effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. Diabetes Care. 2006;29:1071–1076. - PubMed
    1. Wang TD, Chen WJ, Lin JW, Chen MF, Lee YT. Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Am J Cardiol. 2004;93:362–365. - PubMed
    1. Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation. 2002;106:679–684. - PubMed

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