A St Louis cardiologist is calling upon the US FDA to reconsider a black-box warning it placed on ultrasound contrast agents at the end of last year, following a new study she coordinated that shows that the benefits of such agents outweigh the risks.

Dr Melda Dolan (Saint Louis University School of Medicine, St Louis, MO) presented her data during a late-breaking clinical-trials session at the American College of Cardiology 2008 Scientific Sessions last week.

"Based on the results of our study, we believe the FDA should reconsider its stance on contrast agents, because the benefits outweigh the potential, although not established, risk," said Dolan. She maintains that the black-box warning, instituted in October 2007, was issued without a formal examination of the risks and benefits of using the agents.

"Our research indicates that contrast agents can be safely used," she said. Furthermore, her study suggests withholding their use in patients who require them could be detrimental, "leading to a failure to detect life-threatening cardiac events," she noted.

Dolan told that in the week since her presentation she has not heard from the FDA. "There are of course some rumors, but I don't want to predict what they will or won't do based on rumors." She is in the process of preparing a manuscript of her study, which will be combined with data from the Mayo Clinic, to include information on the use of contrast agents in around 40 000 patients, she says.

Dolan explained that contrast agents were introduced during the late 1990s and are administered intravenously in about one in five patients undergoing transthoracic echocardiography, including stress echo, to obtain optimal images.

Contrast agents greatly enhance the quality of the images taken and the doctors' ability to assess cardiac function, she noted.

But last October, following reports of a number of deaths and serious adverse reactions shortly after or during infusion of contrast agents, the FDA placed a black-box warning on such products, and use of the agents plummeted.

There have since been calls for the warning labels to be removed, with experts arguing that the very patients who are excluded from undergoing echocardiograms with these contrast agents are precisely the ones in whom they are needed.

Dolan and her colleagues compared short-term outcomes in almost 24 000 patients undergoing a resting transthoracic echo with a contrast agent with those from approximately 6000 who did not need contrast agents; they found no difference between the groups in deaths or serious adverse events occurring within 30 minutes.

At 24 hours, there were three nonfatal MIs and one death in the contrast-agent group, none of which could be attributed to contrast agents. This compared with seven nonfatal MIs and one death in the 6000 patients who did not get contrast agents.

• They then looked at 4011 patients undergoing stress echo and receiving contrast agents for suboptimal images and 1923 matched patients with optimal image quality without contrast and compared these with angiography for accuracy and sensitivity.
• Those who had the contrast agents reached or exceeded the levels of sensitivity of those who did not.
• Hence, the benefits of contrast use in patients with suboptimal images are significant—they make suboptimal studies equivalent to optimal studies and prevent additional costly tests—and these benefits outweigh the possible risks, said Dolan.

Finally, the researchers assessed use of contrast agents in 6075 patients analyzed to determine the added benefit of myocardial-perfusion imaging with respect to long-term follow-up.

They found that myocardial-perfusion assessment with contrast echo adds significant prognostic value, with these analyses significantly increasing the ability of stress echo to predict adverse events, Dolan emphasized.

"The message that patients should take home from our study is that there are risks to every treatment, from medications to surgery.

But when the benefits of a treatment or test greatly outweigh the risks, it may be worthwhile to take a small risk for a great benefit," she concluded.