Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

Bach, Richard G.; Brooks, Maria M.; Lombardero, M.; Genuth, Saul; Donner, Thomas; Garber, Alan J.; Kennedy, Laurence; Monrad, E. Scott; Pop‐Busui, Rodica; Kelsey, Sheryl F.; Frye, Robert L.

doi:10.1161/circulationaha.112.000678

Cited by 61 publications

(44 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 They point out that, in contrast to our results, previous pooled analyses of randomized trials of rosiglitazone showed a higher incidence of myocardial infarction, and that our observed differences (or rather lack of differences) in cardiovascular outcomes associated with rosiglitazone were potentially attributable to residual confounding. They also raise the point that we did not report a falsification end point that could have assessed the likelihood that observed results were more likely attributable to confounding than true effects.…”

contrasting

confidence: 99%

Response to Letter Regarding Article, “Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial”

et al. 2014

Self Cite

View full text Add to dashboard Cite

We thank Drs Liu, Chen, and Huang for their interest in our article. 1 They point out that, in contrast to our results, previous pooled analyses of randomized trials of rosiglitazone showed a higher incidence of myocardial infarction, and that our observed differences (or rather lack of differences) in cardiovascular outcomes associated with rosiglitazone were potentially attributable to residual confounding. They also raise the point that we did not report a falsification end point that could have assessed the likelihood that observed results were more likely attributable to confounding than true effects.Our study reported prospectively collected longitudinal results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial cohort based on the diabetes mellitus treatment received, and was not a cross-sectional analysis. We agree that there is no substitute for randomization and no observational study, ours included, can fully exclude residual confounding. We should then also note the potential weaknesses of the meta-analysis that first implicated rosiglitazone as a cause of myocardial infarction, and reemphasize the unique aspects of the BARI 2D design and analysis that would be expected to minimize the impact of confounding. Even a well-conducted meta-analysis of limited studies will remain limited, because it is unable to compensate for the weaknesses of the original studies and may even unintentionally conceal those weaknesses. A carefully performed, independent examination of the meta-analysis regarding cardiovascular hazard from rosiglitazone concluded that the risk for myocardial infarction and death for diabetic patients taking rosiglitazone remained uncertain. 2It is within this context that the BARI 2D design and results merit further consideration. In the BARI 2D trial, 3 patients were randomly assigned to a glycemic strategy of insulin sensitization or insulin provision. Therefore, initiation of rosiglitazone was generally determined by treatment assignment rather than patient indication, and the biases seen when the initiation of drug treatment is influenced by severity of illness were minimized. We used propensity-matching to further reduce any baseline differences when comparing treatment groups. Despite this, we did not detect a signal of ischemic cardiovascular harm from rosiglitazone. Similar conclusions were recently confirmed by a thorough FDA review of the independent readjudication of the 1 completed randomized trial designed to test the cardiovascular safety of rosiglitazone. 4A falsification end point is most useful when an association is detected and the goal is to verify that the association is causal and not attributable to residual confounding. For our analyses, such a strategy was not applicable. We did, however, report what might arguably be considered a prespecified, unrelated, verification end point. An increase in bone fractures, especially among women, had been observed in the previous prospective, randomized trials of rosiglitazone. 5,6 In our analy...

show abstract

contrasting

confidence: 99%

Response to Letter Regarding Article, “Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial”

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the RECORD cardiovascular outcome trial, 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone did not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs [44]. Among patients with T2DM 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 [45].…”

Section: B) Hyperglycaemia : Minor Role In a Complex Pathophysiology mentioning

confidence: 99%

Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal

Scheen

Charbonnel

2014

Diabetes & Metabolism

View full text Add to dashboard Cite

Type 2 diabetes mellitus is strongly associated with cardiovascular complications, especially coronary artery disease. Numerous epidemiological studies showed a close relationship between major cardiovascular events and glycaemia and several pathophysiological mechanisms have been described that explain how hyperglycaemia induces vascular damages. However, randomized controlled trials that investigated either an intensive glucose lowering strategy versus standard care or the addition of a new glucose-lowering agent versus a placebo largely failed to demonstrate any clinical benefits in terms of cardiovascular morbidity or mortality. This lack of evidence led some people to contest the clinical efficacy of lowering blood glucose in patients with type 2 diabetes, despite its positive effects on microvascular complications. In this article, we analyze the various reasons that may explain such discrepancies. There are still strong arguments in favour of targeting hyperglycaemia, but avoiding other counterproductive effects, such as hypoglycaemia and weight gain, and integrating the glucose-lowering approach within a global multirisk strategy to reduce the burden of cardiovascular disease in type 2 diabetes.

show abstract

“…It should be noted that the dose of ROSI may be higher as compared to previous studies, in which ROSI was usually administered via oral gavage. Moreover, in a large scale meta-analysis, long-term use of ROSI has been proved to be associated with an increased risk in heart failure and myocardial infarction indicated in type 2 diabetic patients (31), whereas this association has not been supported by subsequent prospective clinical studies (32,33). Considering the controversy of ROSI in clinical practice, its beneficial effect on insulin signaling and hyperglycemia needs to be confirmed in further studies.…”

Section: Discussionmentioning

confidence: 99%

Acute Hepatic Insulin Resistance Contributes to Hyperglycemia in Rats Following Myocardial Infarction

Wang

Liu

Han

et al. 2015

Mol Med

View full text Add to dashboard Cite

Although hyperglycemia is common in patients with acute myocardial infarction (MI), the underlying mechanisms are largely unknown. Insulin signaling plays a key role in the regulation of glucose homeostasis. In this study, we test the hypothesis that rapid alteration of insulin signaling pathways could be a potential contributor to acute hyperglycemia after MI. Male rats were used to produce MI by ligation of the left anterior descending coronary artery. Plasma glucose and insulin levels were significantly higher in MI rats than those in controls. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. However, insulin-stimulated signaling was not altered significantly in skeletal muscle after MI. The relative mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase were slightly higher in the liver tissue of MI rats than those in controls. Rosiglitazone (ROSI) markedly restored hepatic insulin signaling, inhibited gluconeogenesis and reduced plasma glucose levels in MI rats. Insulin resistance develops rapidly in liver but not skeletal muscle after MI, which contributes to acute hyperglycemia. Therapy aimed at potentiating hepatic insulin signaling may be beneficial for MI-induced hyperglycemia.

show abstract

Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

Cited by 61 publications

References 27 publications

Response to Letter Regarding Article, “Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial”

Response to Letter Regarding Article, “Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial”

Effects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal

Acute Hepatic Insulin Resistance Contributes to Hyperglycemia in Rats Following Myocardial Infarction

Contact Info

Product

Resources

About