In a new study, the diabetes drug rosiglitazone was not associated with an increased risk of major cardiovascular events and mortality in diabetic patients who had established CAD….
Richard Bach, MD, of Washington University in St. Louis, and colleagues reported In a post-hoc analysis of data from the BARI 2D trial, patients taking rosiglitazone had an equal likelihood of dying over 5 years as those who didn’t take any drug in the thiazolidinedione (TZD) class (hazard ratio 0.83, 95% CI 0.58 to 1.18, P=0.29)..
The drug also appeared to significantly lower the risk of a composite of death, myocardial infarction (MI), and stroke (HR 0.72, 95% CI 0.55-0.93, P=0.01).
The current publication is an update from data reported at the 2010 American Diabetes Association meeting, and now includes propensity-matched analyses in order to "thoroughly examine the question of whether rosiglitazone was associated with adverse cardiovascular outcomes in BARI 2D."
Bach added that, "Each of the analytic methods employed has strengths and limitations, yet, of note, neither show a significant association of rosiglitazone use with death or MI in this potentially highly vulnerable population of patients with type 2 diabetes and established coronary artery disease (CAD) where long-term cardiovascular outcomes were prospectively collected and carefully adjudicated.
When the data were presented at the 2010 meeting, they were a stark contrast to two other studies reported at the meeting. One was an updated meta-analysis by Steven Nissen, MD, of the Cleveland Clinic, and colleagues, which found a significantly increased risk of MI with use of the drug, and the other was an analysis of FDA data that found a higher risk of a composite of stroke, heart failure, MI, and death.
The release of the updated data comes just months after an FDA advisory panel recommended that the agency loosen restrictions on prescribing the drug, which were set in 2010 after several studies had found an increased risk of MI with use of the drug.
The change of heart was sparked largely by a readjudication of GlaxoSmithKline’s RECORD trial, which turned up results similar to the first analysis: rosiglitazone didn’t increase the risk of a composite of cardiovascular death, MI, and stroke.
In addition to the updated Cox regression models, Bach and colleagues conducted propensity matching to investigate the link between the drug and heart and mortality risk in the dataset, which included 2,368 patients with type 2 diabetes and CAD over a mean 4.5 years of follow-up.
In the Cox analyses, they found that mortality wasn’t significantly different between patients treated with rosiglitazone and those who didn’t get a TZD (1.88 versus 2.56 per 100 patient-years, P=0.08). They also saw lower incidence of the composite of death, MI, and stroke in rosiglitazone patients (3.79 versus 5.81 per 100 patient-years, P=0.002), as well as a lower risk of stroke (HR 0.36, 95% CI 0.16 to 0.86), although there were no significant findings with regard to MI alone.
Cox analyses did, however, reveal a higher incidence of fractures (HR 1.62, 95% CI 1.05 to 2.51, P=0.03) that appeared to be higher among women. Congestive heart failure was also more frequent among patients taking rosiglitazone, but the difference wasn’t significant, they reported.
The propensity matching analyses turned up no significant differences between rosiglitazone users and those who didn’t take a TZD in terms of mortality, in the composite of death, MI, and stroke, for stroke alone, or for congestive heart failure.
"From our examination of over 450 adjudicated ischemic cardiovascular events occurring during 4.5 years of follow-up in BARI 2D and with at least 2,500 patient-years of exposure to rosiglitazone for each endpoint, it is notable that neither analysis suggested that rosiglitazone use was associated with a significant increase in adverse cardiovascular ischemic events, including death or MI," they wrote.
They noted that the BARI 2D trial provided intensive medical therapy for ischemic cardiovascular disease, so results could imply that the drug holds particular benefit among patients who are being intensively managed for cardiovascular disease.
They concluded that their results "contribute prospective longitudinal data regarding outcomes related to treatment with rosiglitazone among high-risk patients."
- Point out that the drug also appeared to significantly lower the risk of a composite of death, myocardial infarction, and stroke.
- Rosiglitazone (Avandia) won’t increase the risk of major cardiovascular events and mortality in diabetic patients who have established coronary artery disease.