Thursday, March 10, 2005

EMERALD Study: No Benefit from Protection Device for Heart Attack Patients
By Julie McKeel

The results of the Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris (EMERALD) study, published in the latest Journal of the American Medical Association, show that devices designed to capture dislodged blood-clot particles (emboli) and reduce complications during primary angioplasty and/or stenting failed to improve blood flow and restoration of the blood supply to damaged tissue, reduce the amount of damage to the heart muscle, or enhance survival in acute heart attack patients.

The DCRI’s Dr. Mitch Krucoff, director of the ECG and Holter Core Laboratory and Dr. Cindy Green, senior statistical advisor, provided the electrocardiographic and angiographic data analyses for this study, while Dr. Peter Berger served on the Data Safety and Monitoring Board.

This study “teaches us a lot about the pathophysiology” of acute heart attacks, according to lead researcher Dr. Gregg W Stone, of Columbia University Medical Center. “Before this study, we were doing a lot of distal protection in acute MI, and now we're not anymore,” Stone told theheart.org. “I think we should be pleased that we conducted a very good, well-run study that showed that this therapy, while it is safe and didn't do any harm, was just not effective."

The EMERALD trial was a multicenter, prospective, randomized study designed to measure the amount of heart-tissue damage 5 to 14 days after primary angioplasty and/or stenting for a heart attack. The study involved 501 patients at 38 academic and community-based centers in 7 countries. The patients were randomized to undergo angioplasty/stenting (percutaneous coronary intervention, or PCI) with the distal protection device or PCI alone. Investigators also sought to determine the frequency of complications and 30-day major adverse cardiac events (MACE).

Investigators effectively removed clot particles in 73% of patients using the protection device. However, removal of debris did not have any significant effect on the amount of tissue damage. There were no significant differences in the frequency of complications, and there was no improvement in event-free survival for those treated with the device.

Stone told theheart.org that he was surprised by the results. While the EMERALD investigators proposed a variety of theories as to why the protection device failed in this study, he suspects the intervention may have been "too little, too late." Embolic-protection devices might not be able to prevent tissue damage in a disease characterized by inflammation, capillary leakage, and reperfusion injury (an injury resulting from the process of restoring the blood supply to damaged heart tissue).

Editorialists commenting on the study for theheart.org credit the EMERALD investigators for conducting the first randomized trial of the usefulness of distal protection during angioplasty in heart attack patients, but they agree that the results do not lend support to the use of the device in these circumstances.

"They [the results] show, in addition, that neither the attractiveness of the therapeutic concept nor the enthusiasm generated by observations from a limited number of patients can replace the need for well-designed randomized clinical trials before advocating the widespread application of new technology," write the editorialists.

On the other hand, Dr Jay Yadav, of the Cleveland Clinic in Ohio, told theheart.org that he thinks the conclusions reached by the investigators may be too broad. He suspects the problem may be specific to the device, as distal-balloon-occlusion devices fail to protect side branches from dislodged clot particles.

"The device was developed for use in the carotid artery where there are no side branches. You can put the distal-balloon-occlusion device anywhere in those segments and you're protecting all of the runoff. But when you get into the coronaries, this is not the case. There are lots of branches, particularly in the left anterior descending artery."

Yadav pointed out that in the Saphenous vein graft Angioplasty Free of Emboli Randomized (SAFER) trial, the use of distal-balloon-occlusion protection was effective and associated with a 42% relative reduction in adverse cardiac events.

The EMERALD investigators note that despite the visible debris extracted from 73% of patients, emboli may still have been created when the angioplasty or stent device first reached the blockage or debris may have moved into unprotected side branches. They report, however, that there was no increase in blocked side branches on angiography in the embolic-protection device group.

"Newer embolic-protection devices are being developed specifically for the coronary arteries. I think a key concept to remember is that we are going to need embolic protection devices for specific organs and anatomies," Yadav told theheart.org. "It doesn't make sense to generalize to every territory, which is what has been done here with this early technology."

Medtronic Corp., maker of the GuardWire Plus device, funded the EMERALD study. Lead investigator Stone has served as a financial consultant to Medtronic Corp. Yadav is the inventor of the Angioguard, a guidewire-based, filter-type embolic-protection device.