PURPOSE:The effects of thiazolidinediones (TZDs) on cardiovascular events remain incompletely characterized. While these insulin sensitizing agents have anti-atherogenic and anti-inflammatory effects, they induce fluid retention and worsen heart failure. Furthermore, a recent controversial meta-analysis suggested that a specific TZD (rosiglitazone) increases ischemic events in average risk populations. However, TZDs remain in widespread use. Our ongoing drug-exposure analysis is designed to assess the impact of rosiglitazone on survival in a high risk diabetic population with significant coronary artery disease (CAD).
METHODS:Information was obtained from the Manhattan Veterans Administration Hospital (MVA) catheterization database, which contained information on 1539 diabetics with CAD referred for cardiac catheterization or revascularization between 1990 and 2005. Clinical variables were recorded at the time of entry into the database. Laboratory and medication data were abstracted from patient charts, and mortality data was available via linking with the social security death index (SSDI). Comparisons were made between the unexposed and exposed rosiglitazone cohorts (with rosiglitazone exposure defined as any uninterrupted use for > 4 weeks). The study was approved by the local institutional review board.
RESULTS:Patients were treated with percutaneous coronary intervention (PCI) (n=705), coronary artery bypass (n=540), or medical management (n=294). Of the patients in the PCI subgroup, 17% were exposed to rosiglitazone for a mean of 30 months. Compared with the PCI non-exposure group, PCI exposed patients had a significantly higher rate of mild left ventricular (LV) dysfunction, a significantly lower rate of severe LV dysfunction, and a trend toward a lower rate of CHF. There were significant differences in the rates of several concomitant therapies. Otherwise the groups were similar at baseline. Unadjusted survival at 60 months was 40% for the unexposed PCI group and 60% for the exposed PCI group.
CONCLUSION:Unadjusted survival was better in the PCI cohort exposed to rosiglitazone. Further analyses, adjusted for covariates and including patients treated medically and surgically, are ongoing.
CLINICAL IMPLICATIONS:These ongoing analyses should further define the aggregate impact of TZDs on diabetics with CAD.
DISCLOSURE:Andrew Zinn, No Financial Disclosure Information; No Product/Research Disclosure Information