Myocardial infarction rosiglitazone

Rosiglitazone has been associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction in several studies. Although causality has not been conclusively established, the FDA has required that a black box warning be added to the labeling. A new longterm study to evaluate potential cardiovascular risks is planned. 

Nissen SE et al Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007 356 2457. [PMID 17517853]... 

Figure 13.3 gives side-by-side forest plots of the results of the two metaanalyses for the placebo-controlled trials for the eight outcomes. For rosiglitazone, the odds ratio estimates were consistently above 1. The 95% confidence interval for myocardial infarction was > 1. For pioglitazone, with... 

Out-patients ( = 39 736) aged 66 years or older who had used either pioglitazone or rosiglitazone were identified from the Ontario Public Drug Benefit Program prescription records [81 ]. Those who had taken pioglitazone had a lower risk of death or hospital admission for either acute myocardial infarction or heart failure compared with rosiglitazone, with an adjusted hazard ratio of 0.8. Further analysis showed that this was due to a reduction in death (adjusted hazard ratio = 0.86) and heart failure (0.77). There was no difference in the risk of acute myocardial infarction (0.95). 

In a case-control study of 9870 cases and 29 610 controls, mean age 63 years, there was difference in the risk of myocardial infarction in those taking pioglitazone compared with rosiglitazone [83 ]. Data were obtained from the Integrated Healthcare Information Services claims database. Cases were defined as people with a diagnosis of myocardial infarction at least 3 months after developing diabetes. 

In a multicenter, open trial in 4447 patients with type 2 diabetes taking metformin or sulfonylurea monotherapy, who were randomized to additional rosiglitazone (n = 2220) or to a combination of metformin and a sulfonylurea (n = 2227), there was a non-significant excess of myocardial infarction (HR 1.14) [97 ]. 

The safety of rosiglitazone has continued to be examined. The 2010 FDA metaanalysis did not include large trials, but included data from 52 studies of 2 months to 2 years duration in a total of 12 069 patients, mean age 58 years, 59% men, with a mean BMI of 30 kg/m [98 ]. The odds ratio for myocardial infarction in those taking rosiglitazone was 1.8 and for congestive heart failure 1.93. These data support the continued concern about the use of rosiglitazone in type 2 diabetes. 

Graham, D.J., Ouellet-Hellstrom, R., MaCurdy, T.E., Ali, F., Sholley, C., Worrall, C., and Kel-man, J.A. 2010. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA The Journal of the American Medical Association, 304(4), 411-418. 

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