Current Atherosclerosis Reports

, Volume 10, Issue 5, pp 398–404

Rosiglitazone and cardiovascular risk



A meta-analysis of 42 clinical trials suggested that rosiglitazone, a widely used thiazolidinedione, was associated with a 43% greater risk of myocardial infarction (P = 0.03) and a 64% greater risk of cardiovascular death (P = 0.06). However, a number of criticisms have been raised that potentially undermine the conclusions of this analysis. In this article, we point out some of these limitations, summarize the currently available evidence concerning rosiglitazone and cardiovascular risk, share implications for drug safety evaluation, and offer practical recommendations to health care providers. We conclude that the data showing the increased risk for myocardial infarction and death from cardiovascular disease for diabetic patients taking rosiglitazone are inconclusive.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356:2457–2471.PubMedCrossRefGoogle Scholar
  2. 2.
    Rosiglitazone: seeking a balanced perspective [editorial]. Lancet 2007, 369:1834.Google Scholar
  3. 3.
    Fuster V, Farkouh ME: Faster publication isn’t always better. Nature Clin Pract Cardiovas Med 2007, 4:345.CrossRefGoogle Scholar
  4. 4.
    McCullough PA, Lepor NE: The rosiglitazone meta-analysis. Rev Cardiovasc Med 2007, 8:123–126.PubMedGoogle Scholar
  5. 5.
    Strom BL: Statements for the hearing record. Committee on Oversight and Government Reform. United States House of Representatives, June 7, 2007. Available at: Accessed on May 17, 2008.
  6. 6.
    Diamond GA, Bax L, Kaul S: Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Ann Intern Med 2007, 147:578–581.PubMedGoogle Scholar
  7. 7.
    Mulrow CD, Cornell J, Localio AR: Rosiglitazone: a thunderstorm from scarce and fragile data. Ann Intern Med 2007, 147:585–587.PubMedGoogle Scholar
  8. 8.
    Bracken MB: Rosiglitazone and cardiovascular risk [letter]. N Engl J Med 2007, 357:937–940.PubMedCrossRefGoogle Scholar
  9. 9.
    Home PD, Pocock SJ, Beck-Nielsen H, et al.: Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N Engl J Med 2007, 357:28–38.PubMedCrossRefGoogle Scholar
  10. 10.
    FDA Briefing Document: Advisory Committee meeting July 30th 2007 to discuss cardiovascular ischemic events with Avandia. Available at Accessed on May 17, 2008.
  11. 11.
    Advisory Committee Briefing Document: Cardiovascular safety of rosiglitazone. Philadelphia: GlaxoSmithKline; 2007. Available at Accessed on May 17, 2008.
  12. 12.
    Psaty BM, Furberg CD: The record of rosiglitazone and the risk of myocardial infarction. N Engl J Med 2007, 357:67–69.PubMedCrossRefGoogle Scholar
  13. 13.
    Singh S, Loke YK, Furberg CD: Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 2007, 298:1189–1195.PubMedCrossRefGoogle Scholar
  14. 14.
    Richter B, Bandeira-Echtler E, Bergerhoff K, et al.: Rosiglitazone for type 2 diabetes mellitus. Cochrane Database Syst Rev 2007; Issue 3. Art No: CD006063. DOI: 10.1002/14651858.CD006063.pub2.Google Scholar
  15. 15.
    Lago RM, Singh PP, Nesto RW: Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet 2007, 370:1129–1136.PubMedCrossRefGoogle Scholar
  16. 16.
    Shuster JJ, Jones LS, Salmon DA: Fixed vs. random effects meta-analysis in rare event studies: the rosiglitazone link with myocardial infarction and cardiac death. Stat Med 2007, 26:4375–4385.PubMedCrossRefGoogle Scholar
  17. 17.
    McAfee AT, Koro C, Landon J, et al.: Coronary heart disease outcomes in patients receiving antidiabetic agents. Pharmacoepidemiol Drug Saf 2007, 16:711–725.PubMedCrossRefGoogle Scholar
  18. 18.
    Rosen C: The rosiglitazone story: lessons from an FDA advisory committee meeting. N Engl J Med 2007, 357:1–3.CrossRefGoogle Scholar
  19. 19.
    Lipscombe LL, Gomes T, Lévesque LE, et al.: Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA 2007, 298:2634–2643.PubMedCrossRefGoogle Scholar
  20. 20.
    Wood S: FDA advisory panels acknowledge signal of risk with rosiglitazone but stop short of recommending its withdrawal. Available at: Accessed on January 20, 2008.
  21. 21.
    European Medicines Agency confirms positive benefit-risk balance for rosiglitazone and Pioglitazone. Doc. Ref. EMEA/484277/2007. Available at: Accessed on May 17, 2008.
  22. 22.
    FDA adds boxed warning for heart-related risk to anti-diabetes drug Avandia. Available at Accessed on May 17, 2008.
  23. 23.
    The Action to Control Cardiovascular Risk in Diabetes Study Group: Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008, 358:2545–2559.CrossRefGoogle Scholar
  24. 24.
    Questions and Answers: Use of Rosiglitazone (Avandia) in the National Heart, Lung, and Blood Institute’s Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trials. Available at Accessed on May 17, 2008.
  25. 25.
    Beals JK: VA diabetes trial shows that intensive glucose control has little effect on cardiovascular risk. Available at: Accessed on June 18, 2008.
  26. 26.
    Dormandy JA, Charbonnel B, Eckland DJ, et al.: Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PRO spective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005, 366:1279–1289.PubMedCrossRefGoogle Scholar
  27. 27.
    Dargie HJ, Hildebrandt PR, Riegger GA, et al.: A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association functional class I or II heart failure. J Am Coll Cardiol 2007, 49:1696–1804.PubMedCrossRefGoogle Scholar
  28. 28.
    Lincoff AM, Wolski K, Nicholls SJ, Nissen SE: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 2007, 298:1180–1188.PubMedCrossRefGoogle Scholar
  29. 29.
    Johannes CB, Koro CE, Quinn SG, et al.: The risk of coronary heart disease in type 2 diabetic patients exposed to thiazolidinediones compared to metformin and sulfonylurea therapy. Pharmacoepidemiol Drug Saf 2007, 16:504–512.PubMedCrossRefGoogle Scholar
  30. 30.
    Goldberg RB, Kendall DM, Deeg MA, et al.: A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2005, 28:1547–1554.PubMedCrossRefGoogle Scholar
  31. 31.
    Avorn J: Keeping science on top in drug evaluation. N Engl J Med 2007, 357:633–635.PubMedCrossRefGoogle Scholar
  32. 32.
    Committee on the Assessment of the US Drug Safety System. Baciu A, Stratton K, Burke SP, (eds): The Future of Drug Safety: Promoting and Protecting the Health of the Public. Washington, DC: National Academies Press; 2006.Google Scholar
  33. 33.
    Vicari KA: Cancer Drugs: No Remission for FDA Omission. Wall Street Journal, August 16, 2007.Google Scholar
  34. 34.
    Strom BL: How the US drug safety system should be changed. JAMA 2006, 295:2072–2074.PubMedCrossRefGoogle Scholar
  35. 35.
    Approval letter. Application number 021071. Center for Drug Evaluation and Research. Available at: Accessed on May 17, 2008.
  36. 36.
    The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008, 358:2545–2559.CrossRefGoogle Scholar
  37. 37.
    Final PDUFA Recommendations Transmitted to Congress Will Strengthen Drug Review and Drug Safety. Available at Accessed on May 17, 2007.
  38. 38.
    Price D, Jefferson T, Demicheli V: Methodological issues arising from systematic reviews of the evidence of safety of vaccines. Vaccine 2004, 22:2080–2084.PubMedCrossRefGoogle Scholar
  39. 39.
    American Diabetes Association: Standards of medical care in diabetes-2008. Diabetes Care 2008, 31(Suppl 1):S12–S54.CrossRefGoogle Scholar
  40. 40.
    UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998, 352:854–865.CrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Division of CardiologyCedars-Sinai Medical CenterLos AngelesUSA

Personalised recommendations