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Rosiglitazone (Avandia) is a thiazolidinedione drug used to treat type 2 diabetes. While this drug is known to precipitate congestive heart failure, its effect on coronary events is unclear. This meta-analysis of 42 randomized published and unpublished trials examined the effect of rosiglitazone on myocardial infarction and cardiovascular death. The trials included 28,000 patients, generally lasted 6 to 12 months, and compared rosiglitazone with other glucose-lowering drugs or placebo.
Overall, the incidence of MI was about 0.6%, and the incidence of cardiovascular death was about 0.3%. Rosiglitazone was associated with a significantly increased risk for MI, compared with risk among controls (odds ratio, 1.43; P=0.03). In addition, an increased risk for cardiovascular death in the rosiglitazone group almost reached statistical significance (OR, 1.64; P=0.06).
Nissen SE and Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007 Jun 14; [e-pub ahead of print]. (http://content.nejm.org/cgi/content/full/NEJMoa072761)
Psaty BM and Furberg CD. Rosiglitazone and cardiovascular risk. N Engl J Med 2007 Jun 14; [e-pub ahead of print]. (http://content.nejm.org/cgi/content/full/NEJMe078099)
Comment
This meta-analysis has several methodologic limitations, acknowledged by the authors and editorialists; nonetheless, the results alert us to the possibility that rosiglitazone may increase risk for coronary events. A key question is whether the new findings represent a “class effect” of all thiazolidinedione drugs; perhaps tellingly, another thiazolidinedione (muraglitazar) was associated with increased cardiovascular morbidity (Journal Watch Nov 29 2005) and was not marketed in the U.S.
For now, clinicians have several options. One is to stop rosiglitazone and consider other drug classes, if necessary. A second option is to substitute pioglitazone (Actos), the other thiazolidinedione available in the U.S. This drug was associated with a small reduction in a composite of death, MI, and stroke (but an increase in heart failure) in a recent trial (Journal Watch Nov 8 2005) and is associated with better lipid profiles than rosiglitazone. With this option, patients should understand that a comprehensive analysis of pioglitazone’s effect on coronary events has not been undertaken. A third option is to continue rosiglitazone in patients who appear to have benefited from it, as long as patients understand that MI risk may be increased and that alternative treatments are available. The FDA has issued a safety alert on rosiglitazone.