Agent Coronary DCB Gets FDA Approval for In-Stent Restenosis

A paclitaxel-coated device, Agent, has become the first coronary DCB in the United States to be approved for the treatment of in-stent restenosis (ISR), Boston Scientific announced today.

The Food and Drug Administration’s decision comes just about 4 months after investigators from the AGENT IDE trial reported an interim analysis of the first 480 patients that showed less TLF at 12 months with the DCB compared with uncoated balloon angioplasty (17.9% vs 28.7%; P = 0.006). The difference was driven by a relative halving of the risks of TLR and target-vessel MI.

The Agent DCB had been granted breakthrough device designation by the FDA in 2021. In their announcement today of the approval, Boston Scientific said the device addresses “a critical unmet need” as the first approved dedicated treatment option for ISR.

This announcement caps years of waiting by American operators, who have watched impatiently as usage grew in other parts of the world: DCBs have had a class I recommendation for in-stent restenosis in European guidelines for the last decade. The devices are already approved for use in Europe, parts of Asia Pacific, and Latin America for the treatment of ISR and previously untreated small vessel coronary disease. According to Boston Scientific, the DCB has been used in more than 100,000 patients in both clinical and commercial settings.

“We've really lagged behind the rest of the world in terms of having this available to us,” said AGENT IDE principal investigator Robert Yeh, MD (Beth Israel Deaconess Medical Center, Boston, MA). “Now that we have it, physicians will be able to offer better treatments to their patients.”

Both Yeh and AGENT IDE study chair Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), told TCTMD that one thing that was clear from the trial was that many patients had multiple instances of restenosis, with 40% of participants having multiple layers of previously placed stents.

“So, that's a natural fit for a technology like a drug-coated balloon,” Kirtane said. “What was nice in the AGENT trial is we did show that the effect was consistent, irrespective of whether it was single layer or multilayer in-stent restenosis,” he added.

Based on the trial experience, Yeh and Kirtane said the most important thing for operators to know about using the DCB is that it’s crucial to treat the lesion as optimally as possible in the lead-up to deploying it.

“If a physician reads this news and says I'm just going to directly put in the Agent balloon and inflate and be done, that is not how it should be used and . . . the likelihood of failure is higher. I think what people need to do is they need to image, figure out why the stent failed, optimize whatever they can optimize—whether they expand further, balloon further, or whatever—and then when they're done, deploy the Agent balloon. That's the way it was done in the study,” Kirtane added.

“This is definitely not a one-stop shop angioplasty treatment,” Yeh concurred. “The fact that patients restenose in the first place is often due to the fact that PCI may not have been optimized. It’s critically important to make sure that the stent is really well expanded, and to me that starts with doing intravascular imaging to understand the mechanism of failure, and then really making sure that before the application of the drug-coated balloon, that you've really achieved the adequate expansion and lumen area that is necessary to ensure a good outcome.”

Yeh added that how operators use intravascular imaging to learn from the treatment of ISR with the DCB is going to be a critical part of the story moving forward.

While today’s approval is specific to ISR, Kirtane said it sets the stage for additional uses aimed at limiting the amount of metal being put into patients. One example could be diffuse LAD disease, where a stent could be used proximally and the DCB used in the mid to distal segments.

“Intuitively, from a patient standpoint, that also sounds good,” he observed. “We obviously have to develop the data and the evidence base to support those types of practices.”

Yeh added that having a DCB also could be helpful for treating bifurcation lesions where “there are limitations in terms of the things that we can do if that bifurcation stent were to restenose.”