Is your patient still using rosiglitazone?

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Is your patient still using rosiglitazone?

J Fam Pract. 2011 May;60(5):282-284

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References

1. Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med. 2010;170:1191-1201.

2. 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.

3. Rosen CJ. The rosiglitazone story—lessons from an FDA Advisory Committee meeting. N Engl J Med. 2007;357:844-846.

4. Iskowitz M. Exclusive: Takeda launches Actos DTC campaign today. Medical Marketing Media. July 15, 2010. Available at: http://www.mmm-online.com/exclusive-takeda-launches-actos-dtc-campaign-today/article/174652/. Accessed April 11, 2011.

5. US Food and Drug Administration. Safety: Avandia (rosiglitazone): REMS – risk of cardiovascular events. Updated February 4, 2011. Available at: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm226994.htm. Accessed April 11, 2011.

6. Harris G. Glaxo agrees to post results of drug trials on web site. NY Times. August 27, 2004. Available at: http://www.nytimes.com/2004/08/27/business/glaxo-agrees-to-post-results-of-drug-trials-on-web-site.html?scp=1&sq=glaxo+agrees+to+post&st=nyt%3e.

7. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373:2125-2135.

8. Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096-1105.

9. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427-2443.

10. Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee. Summary Minutes of the joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. Gaithersburg, MD: US FDA, July 2010 (last updated January 6, 2011). Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM241505.pdf. Accessed February 14, 2011.

11. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279-1289.

12. Lincoff AM, Wolski K, Nicholls SJ, et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298:1180-1188.

13. US Food and Drug Administration. FDA briefing document. Division of Metabolism and Endocrine Products and Office of Surveillance and Epidemiology. July 30, 2007. Available at: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-02-fda-backgrounder.pdf. Accessed April 17, 2011.

14. US Senate Committee on Finance. Grassley, Baucus release committee report on Avandia. Senators’ letter to the FDA with attachments. Feb. 20, 2010. Available at: http://finance.senate.gov/newsroom/chairman/release/?id=bc56b552-efc5-4706-968d-f7032d5cd2e4. Accessed April 17, 2011.

15. Lipska KJ, Ross JS. Switching from rosiglitazone: thinking outside the class. JAMA. 2011;305:820-821.

At an FDA advisory committee meeting in July 2010, the recommendation to remove rosiglitazone from the market received a plurality of votes. That recommendation was not carried out, however because 4 other options—all of which involved leaving rosiglitazone on the market—taken together, received more votes.¹⁰

We think this meta-analysis provides substantial doubt about the safety of rosiglitazone. If there is a safer alternative, the decision not to use rosiglitazone becomes even easier. An important question, then, is whether the other thiazolidinedione on the market, pioglitazone (Actos), carries similar risks.

The PROACTIVE trial, a large cardiovascular outcomes study published in 2005,¹¹ and a patient-level meta-analysis of cardiovascular outcomes published in 2007,¹² assessed the risk of death, MI, and stroke in a diverse population of patients taking pioglitazone. Compared with studies of cardiovascular events associated with rosiglitazone, the PROACTIVE trial and the meta-analysis showed that pioglitazone has a significantly lower risk of death, MI, or stroke.

For patients who are doing well on rosiglitazone, a within-class switch to pioglitazone would appear to decrease coronary artery events. However, it must be noted that both drugs have a black box warning regarding congestive heart failure. (The black box warning for rosiglitazone now identifies the increased risk of MI, as well).⁵

CAVEATS: Missing data weaken analysis

The authors of the meta-analysis reported here were unable to obtain individual patient outcomes, which would have allowed them to do a more powerful analysis. However, other meta-analyses, including one from the FDA,¹³ found similar results.

CHALLENGES TO IMPLEMENTATION: Patients and physicians may be reluctant to switch

FAST TRACK

An in-class switch to pioglitazone appears to decrease cardiovascular events.

Theoretically, a switch to pioglitazone is an easy choice, as it is the same class of medication as rosiglitazone but has a lower risk of MI. The use of rosiglitazone caused about 83,000 excess MIs between 1999 and 2007, the FDA estimated.¹⁴ That number has since been downgraded to up to 6000 excess MIs annually to reflect the reduced usage of the drug.^1,14 But when patients are doing well on a particular medication, neither they nor their doctor may want to change to another drug, especially when the adverse effects of the current medication are uncommon. Nonetheless, reevaluation of their diabetic medication regimen often gives patients an opportunity to ensure that they are taking the best first-line agent—which in many cases is metformin, and not a thiazolidinedione at all.¹⁵

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.