Clues to Avandia Heart Failure Risk UncoveredSep 7, 2007
Avandia and other drugs in its class that are used to treat Type II diabetes have been linked to increased risk of heart failure, but the reasons behind this deadly side effect were poorly understood. Now, an experiment involving mice has given researchers clues to the reasons behind this heart failure connection. The study, conducted by researchers at the Columbia College of Physicians and Surgeons, found that PPARg agonists like Avandia can increase the uptake of both glucose and triglycerides in cardiac tissue. Such an occurrence can lead to or exacerbate heart failure, and the mice in the study developed cardiomyopathy.
To evaluate the effects of Avandia on the heart, the researchers used two types of mice. The mice were bred to over-express PPARg, the nuclear receptor that is targeted by drugs like Avandia. Some mice were bred to over-express PPARg at high-levels, while the other group over-expressed it at lower levels. The mice were also bred to have dilated left ventricles, impaired systolic function and increased heart-to-body ratios and other signs associated with heart failure. When the mice were exposed to Avandia, the treatment caused further deterioration of heart function including lipid accumulation and larger hearts.
When the researchers compared PPARg expression levels in the hearts of the mice and human hearts, they found that the expression in human hearts was greater. This would suggest that PPARg has a bigger impact on human hearts. The researchers wrote that “While PPARg antagonists appear to have multiple beneficial affects, their direct actions on the myocardium have the potential to lead to deterioration in heart function.”
Avandia carries a black box warning about its potential to cause or exacerbate heart failure, and it is not recommended for patients with heart failure. The drug became a subject of controversy in May when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack. Earlier this summer, the Food & Drug Administration (FDA) convened an advisory panel to look into safety issues surrounding Avandia. The panel found that patients using the drug did face a greater risk of heart attack, and recommended that its label include the strongest FDA warning possible regarding this risk. However, the panel stopped short of recommending that Avandia be pulled from the market. The panel also said that there was a need for more studies on the safety issues surrounding Avandia.