Rosiglitazone associated with higher mortality rate versus pioglitazone

Rosiglitazone was associated with an increased risk of all-cause mortality and congestive heart failure (CHF) compared with pioglitazone in an inception cohort study of patients aged >65 years. Patients treated with rosiglitazone or pioglitazone demonstrated similar rates of myocardial infarction (MI) and stroke. These results were published in the Archives of Internal Medicine.

Study investigators assessed medical claims data from the New Jersey Pharmaceutical Assistance for the Aged and Disabled program from January 1, 1999, through December 31, 2004, and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly program from January 1, 1999, through December 31, 2005. These data were merged with Medicare Parts A and B claims. The programs had no restrictions or prior-authorization programs in place for rosiglitazone or pioglitazone. Patients aged >65 years were included in the study if they had initiated treatment with either rosiglitazone or pioglitazone for diabetes during the study period. The primary outcome was all-cause mortality. Secondary outcomes were MI, stroke, and hospitalization for CHF.

A total of 28,361 patients were included in the study; 14,260 were treated with pioglitazone and 14,101 were treated with rosiglitazone. The baseline characteristics of these 2 groups were similar. During 29,060 person-years of follow-up, 1,869 patients died. After adjusting for multiple covariates, the investigators observed that rosiglitazone-treated patients had a 15% (95% CI, 5%-26%) higher mortality rate than pioglitazone-treated patients. Rosiglitazone-treated patients also demonstrated a 13% (95% CI, 1%-26%) greater risk of CHF than pioglitazone-treated patients. There was no significant difference between the 2 drugs in the outcomes of MI and stroke. These results were consistent across patient subgroups.

In their discussion of the study results, the authors pointed out the apparent discrepancy in these data: “if rosiglitazone use increases all-cause mortality compared with pioglitazone but no differences in diagnosed MI and stroke are observed between these drugs, what is the mechanism for this harmful mortality effect?” The authors hypothesized that many of the deaths were caused by MI or stroke but that these deaths may have occurred suddenly or before a diagnosis was made. They concluded, “This study confirms the safety concerns that have been raised for rosiglitazone compared with pioglitazone, which, in turn, also cannot be considered a very safe drug given its well-documented effect on the risk of CHF.”

Source
Winkelmayer WC, Setoguchi S, Levin R, Solomon DH. Comparison of cardiovascular outcomes in elderly patients with diabetes who initiated rosiglitazone vs pioglitazone therapy. Arch Intern Med. 2008;168:2368-2375.