To address their diabetes, the same patients were randomly assigned to receive either insulin-providing drugs (such as insulin itself) or insulin-sensitizing drugs (such as rosiglitazone or another drug, metformin). As a result, a large number of patients were treated with rosiglitazone during approximately five years of follow up in the trial. This aspect of BARI 2D provided a way to investigate rosiglitazone's cardiovascular safety after it came under scrutiny in 2007. In addition, Bach notes the importance of this new analysis because it looks at a population of patients already at high risk of cardiovascular events like heart attack and stroke.

Compared with patients not receiving a TZD, those who did take rosiglitazone showed a 28 percent lower combined rate of death, heart attack and stroke. In addition, the rate of stroke on its own was 64 percent lower in patients receiving rosiglitazone. Both of these differences were statistically significant. Rates of heart attack and death on their own showed no significant difference between those who took rosiglitazone and those who did not. In line with other studies, rosiglitazone was associated with increased risk of bone fracture, especially in women.

While these results support rosiglitazone's safety in patients with existing heart disease, Bach points out a weakness in the new analysis. Because BARI 2D was designed to assess treatment strategies, not the safety of rosiglitazone, the drug was not randomly assigned. It was the treating physician who decided whether to prescribe rosiglitazone to a particular patient, in line with the study protocol.

"It's not a pure randomly assigned trial of rosiglitazone versus a different drug," Bach says. "Our post-trial analysis compared patients treated with rosiglitazone to patients not receiving any TZD drug. That included patients in both arms - the insulin-providing and insulin-sensitizing arms," he says.

Like many diabetes drugs, rosiglitazone's FDA approval in 1999 was based on the fact that it improves glucose control, Bach explains. "We also have to be very careful about any additional adverse consequences or side effects of those drugs," he says. "We're always balancing risk versus benefit. Our particular data do not suggest that harm exceeds the potential benefit for rosiglitazone in patients with diabetes and established coronary artery disease."

Source: Washington University School of Medicine