The thiazolidinediones rosiglitazone and pioglitazone and the risk of coronary heart disease: a retrospective cohort study using a US health insurance database.

Background: The thiazolidinediones (TZDs), including rosiglitazone maleate and pioglitazone hydrochloride, are commonly prescribed in patients with type 2 diabetes mellitus. Although recent meta-analyses suggest there is an increased risk of myocardial infarction (MI) among rosiglitazone users, these findings were not supported by data from other studies.

Objective: The goal of this research was to compare the risk of MI, coronary revascularization (CR), and sudden death in patients who began rosiglitazone therapy versus those who began pioglitazone therapy.

Methods: This was a retrospective cohort study using information from a large health care database (with data available on approximately 14 million individuals). All initiators of rosiglitazone or pioglitazone from July 1, 2000, through March 31, 2007, for whom the first dispensing followed >or=6 months of health plan membership and the member's 18th birthday were identified. The propensity score method was used to create matched cohorts of patients in 3 treatment groups: TZD monotherapy, dual therapy (a TZD plus another antidiabetic agent), and TZD therapy with concomitant insulin. Follow-up continued to a change in treatment regimen, defined as regimen switch (ie, the addition of any antidiabetic agent to an existing regimen) or regimen stop (ie, the discontinuation of any component of the therapeutic regimen). Three outcomes that represent coronary heart disease were assessed for this analysis: MI, CR, and sudden death. The proportional hazards model, stratified by therapeutic regimen, was used to estimate hazard ratios (HRs) and 95% CIs of coronary heart disease risk associated with use of rosiglitazone relative to pioglitazone.

Results: Among 47,501 matched pairs of rosiglitazone and pioglitazone users, 72,104 (75.9%) were receiving TZD monotherapy, 17,822 (18.8%) were receiving dual therapy, and 5076 (5.3%) were receiving TZD therapy with insulin. Mean follow-up was 9.6 months with regimen switch as the censoring event and 8.4 months with regimen stop as the censoring event. For MI, the HR was 1.35 (95% CI, 1.12-1.62) through regimen switch and 1.41 (95% CI, 1.13-1.75) through regimen stop. For the composite outcome of MI, CR, and/or sudden death, the HR was 1.09 (95% CI, 0.97-1.22) through regimen switch and 1.12 (95% CI, 0.98-1.27) through regimen stop.

Conclusions: In this retrospective cohort analysis, MI was more common in users of rosiglitazone than in users of pioglitazone. The incidence of a combined end point of MI, CR, and/or sudden death in patients receiving rosiglitazone was not significantly different from that in patients receiving pioglitazone.