The FDA’s warning on echo contrast agents galvanized physicians and sonographers to fight back. They enjoy a partial victory, but the fight is still on to prove safety and efficacy.
The echocardiography community responded vociferously in the negative to the FDA’s 2007 black box warning on the two U.S. approved echo contrast agents: Definity (Lantheus Medical) and Optison (GE Healthcare). To its credit, the FDA responded to the clinical pressure and changed the warning a year later to a less restrictive one. Since that time, cardiologists across the country have continued to use these agents, collecting data to prove their safety and efficacy.
“I think the black box warning is overly conservative. Echo contrast is clearly very safe,” says Michael Farrar, MD, director of the noninvasive lab at North Kansas City Hospital in North Kansas City, Mo. Farrar handles about 30,000 echocardiograms a year, one-quarter of which require the use of contrast.
Whether the FDA further revises or removes the black box warning won’t overly affect Farrar and colleagues. Where the warning will have the most impact, he says, are in labs that order contrast through the pharmacy, instead of the cardiology department. “Pharmacies and pharmacists by their nature will be more concerned about the black box warning, rather than the clinicians who are actually using it on a day-to-day basis to make clinical decisions,” he says.
Like many facilities, North Kansas City Hospital has a sonographer-driven protocol for the use of contrast. If a patient has relative contraindications, however, such as pulmonary hypertension, respiratory failure, patent foramen ovale (PFO) or a recent acute event, sonographers consult with the cardiologist.
A sonographer-driven contrast protocol leads to improved workflow and patient management. “I tell my staff that if they have a technically challenging patient who may require contrast, make that decision up front rather than struggling through the whole exam,” says Karl Q. Schwarz, MD, director, echocardiography and mobile echocardiography services at the University of Rochester Medical Center in New York. “A suboptimal exam carries a burden with it that is ongoing,” particularly for referring physicians if the patient returns with chest pain.
Prior to stress echo contrast reimbursement, Schwarz and colleagues conducted a study to determine contrast’s efficacy (J Am Soc Echocardiogr 2004;17(1):15-20). He says they were “very judicious in contrast use so as not to lose too much money.” Contrast was used in about 10 to 15 percent of patients, which were “the toughest of the tough,” Schwarz says. Researchers achieved diagnostic images in more than 90 percent of the nearly 300 patients, but they also had a better than 95 percent negative predictive value. “If we have a test that can rule out cardiac pathology as the cause of pain, that’s very helpful,” he adds. Now Schwarz and colleagues use contrast in about half of the stress echo patients—“the tough cases, but also in those with limited pictures as well.”
Softer, but still chilling
Even though the FDA “softened” the black box warning, it continues to have a chilling effect on use, says Michael L. Main, MD, director, echocardiography at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. “Many clinicians have medico-legal concerns. They know that these agents are safe in comparison to other contrast agents and other tests, but they are concerned. Many labs that have previously used echo contrast agents have stopped altogether and have not resumed even after the modification last year.”
Since those initial warnings, many large safety studies have been published, signaling the appearance of safe agents. At the 2009 American College of Cardiology meeting, Main presented the results of a retrospective study of nearly 40,000 severely ill patients, some 20,000 of whom received contrast (78 percent Definity, 22 percent Optison). Patients who received contrast had a 26 percent lower risk of short-term mortality within 48 hours after the exam. Analysis of a subset using mechanical ventilation also showed lower short-term mortality rates for those receiving contrast. Another Main et al retrospective study of more