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 57th Annual Scientific Session 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 heartwire 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.

Use of contrast agents plummets since warning

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.

As reported by heartwire, 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.

Benefits of contrast agents outweigh risks

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.