Off-label gadolinium use during CMR linked to low incidence of adverse events in European registry

Off-label use of gadolinium-based contrast agents in cardiac magnetic resonance appeared safe regarding frequency, manifestation and severity of acute events, according to an analysis of the EuroCMR Registry.

Among 17,767 patients who received a mean dose of 25.6 mL of gadolinium-based contrast agent in the European Cardiovascular Magnetic Resonance (EuroCMR) registry, 0.17% (n=30) experienced acute adverse reactions during and immediately after the cardiac magnetic resonance (CMR) procedure.

The reactions were considered mild, with the most frequent complaints being rashes and hives (nine of 30), nausea (seven of 30) and anxiety (six of 30). Event rates ranged from 0.06% to 0.47%, but researchers found individual event rates and specific characteristics of the agents showed no relation.

“The use of magnetic resonance imaging to assess the heart is a relatively new technique and is increasingly used in the United States and Europe,” study researcher Anja Wagner, MD, of Hahnemann University Hospital, Drexel University College of Medicine, Philadelphia, told Cardiology Today. “We found that the incidence of acute adverse reactions after administration of gadolinium-based contrast was not different from the incidence in the FDA-approved general radiology setting. Thus, the use of gadolinium-based contrast in CMR should be regarded as safe concerning the frequency, manifestation and severity of acute events.”

Off-label status

Currently, there are six gadolinium-based contrast agents approved by the FDA for patients undergoing MRI, with gadobutrol (Gadavist, Bayer Pharmaceuticals) recently approved in March. However, gadolinium-based contrast agents for patients undergoing CMR are still off-label.

According to Wagner, “Gadolinium-based contrast agents are frequently used in noncardiac and CMR imaging; however, the safety of gadolinium-based contrast agents have only been studied and are FDA-approved for noncardiac imaging. Therefore, the use of gadolinium-based contrast agents to assess the heart is considered ‘off-label’ in Europe and the United States.”

According to the researchers, there is a relatively low incidence of adverse reactions vs. iodinated contrast agents used for CT, but “the frequency, manifestation and severity of acute adverse reactions associated with gadolinium-based contrast agents in the specific setting of CMR have not been systematically evaluated yet.

“Despite the fact that there currently is no FDA approval of gadolinium for CMR in the US and many European countries, the off-label use does not bring any additional risks for the patient,” they concluded. “In fact, datasets such as this, when combined with efficacy studies, may facilitate FDA approval for gadolinium in CMR in the future.”

The future with gadolinium

Natalie Bello, MD, of the department of medicine, and Warren J. Manning, MD, of the department of radiology, both at Beth Israel Deaconess Medical Center and Harvard Medical School, said although the EuroCMR registry confirms the safety of using gadolinium contrast in CMR, a CMR registry in the US and worldwide would only benefit gadolinium in CMR research.

“[A worldwide registry] would enable monitoring of indications for CMR, use of and reaction to contrast agents, as well as adherence to appropriateness criteria,” Bello and Manning wrote in an accompanying editorial. “The registry may also serve as a platform for cost-effective analyses of the down-stream testing impact of CMR.”

Wagner said the EuroCMR registry and similar registries are helpful because they include large numbers of patients and reflect “real-world medicine.” – by Casey Murphy

For more information:

• Bello N. J Am Coll Cardiol Img. 2011;4:1177-1179.
• Bruder O. J Am Coll Cardiol Img. 2011;4:1171-1176.

Disclosure: One of the study researchers reports receiving research support from Bayer-Schering. Drs. Bello and Manning report no relevant financial disclosures.

W. Gregory Hundley

This study demonstrates the benefits associated with research using registry and longitudinal follow-up data. Expanding this type of research throughout the United States could further [help researchers] understand suitability of gadolinium use in MRI of the CV system.

– W. Gregory Hundley, MD
Cardiology Today Editorial Board Section Editor

Disclosure: Dr. Hundley receives contrast from Bracco diagnostics for research purposes.

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