Treatment options for in-stent restenosis are limited and often unsuccessful, so there was a lot of excitement when data from the first large U.S. randomized trial for a coronary drug-coated balloon (DCB) for this indication was presented at TCT 2023 in San Francisco.
The pivotal AGENT IDE trial found that the device reduced ischemia-driven target lesion revascularization rates by 50%, cutting them from 24% to 12%. Importantly, it also halved the rates of target vessel myocardial infarction, reducing them from 12% in the conventional balloon angioplasty group to 6% in the AGENT balloon group. Additionally, the AGENT balloon showed an excellent safety profile, with no occurrences of stent thrombosis, a significant concern in the alternative treatment arm.
Cardiovascular Business spoke with the principal investigator and presenter of the study results, Robert Yeh, MD, the director of the Richard A. and Susan F. Smith Center for Outcomes Research, section chief of interventional cardiology at the Beth Israel Deaconess Medical Center, and the Katz-Silver Family Professor of Medicine at Harvard Medical School. He said the device marks a significant milestone in the battle against coronary artery disease with a first-of-its-kind therapy in the United States.
"It turns out that in the United States, more than 10% of all of our percutaneous coronary interventions (PCIs) are actually conducted for stent re-stenosis. So this remains a prevalent problem despite the improvements in drug-eluting stent technology, and we don't have a lot of good treatments for this. Typically, patients receive another layer of drug-eluting stent in there, but patients often have two or three or even four layers of stent in there for which additional metal is not a good option for them. There are other options like balloon angioplasty, the competitor arm in this study, or radiation brachytherapy, which is not available in most U.S. centers," Yeh explained.
He said the Boston Scientific Agent DCB may offer an easy-to-use solution for restenosis. The results of this investigational device exemption (IDE) trial will be submitted to the FDA for review.
"Positive outcomes in this complex trial population – from the markedly lower rate of target lesion failure to the significant reduction in heart attack and no stent thromboses – support the Agent DCB as an alternative treatment option for coronary in-stent restenosis," said Yeh. "Meaningful therapy advancements for this condition are critical, and the ability to reduce the risk of restenosis without using radiation or introducing another layer of metal stenting is a promising step forward."
Understanding the challenge of in-stent restenosis
In-stent restenosis refers to the recurrence of narrowed or blocked arteries within previously placed stents. This is caused by neo-intimal hyperplasia, which is seen in some patients as the body reacts to vessel trauma from angioplasty or to the stent with an overgrowth of scar tissue that can re-occlude the vessel segment. Despite significant advancements in drug-eluting stents (DES) technology, which use an anti-proliferative drug coating to prevent hyperplasia, it still occurs in some patients.
The Agent DCB is a a semi-compliant balloon designed to deliver the anti-proliferative drug paclitaxel to stop and prevent further tissue overgrowth. The complex part of making a drug-eluting balloon where most of the research and development is centered is on the excipient. That carries the drug through the blood without the drug washing away. It also has properties to allow it to quickly deliver the drug into the tissue one the balloon is expanded.
"These aren't easy devices to make. These are what the FDA refers to as drug device combination products, and they're challenging to make. That's one of the reasons we don't have one available in the United States. There are new technologies that are coming out that are trying different drugs. But we think that paclitaxel is going to be the one that's most effective for the unique properties. This is not a class effect for all these devices. In fact, these devices differ from one to another," Yeah explained.
The AGENT IDE trial results
The AGENT IDE trial compared the efficacy of the paclitaxel-eluting Agent balloon with conventional balloon angioplasty in treating in-stent restenosis. This first data presented at TCT were one-year outcomes for 480 patients, but the final results of there trial will include up to 600 patients.
The primary outcome of the trial was the occurrence of target lesion failure, a composite endpoint including ischemia-driven target lesion revascularization (TLR), target vessel myocardial infarction, and cardiac death assessed at one year. Patients treated with conventional balloon angioplasty exhibited a significantly higher event rate of 28.7% compared to 17.9% in those treated with the Agent DCB. This represents a 37% relative risk reduction and a 10% absolute risk reduction, with a highly significant P value of 0.0063, Yeh said. This demonstrated the superiority of the Agent balloon in treating in-stent restenosis.
These differences were mainly driven by significantly reduced rates of myocardial infarction related to the target vessel (TV-MI) and the need for a repeat TLR procedure. Overall, data demonstrated an approximate 38% relative risk reduction in TLF. Additional 12-month event rates for the Agent DCB vs. uncoated balloon included zero definite/probable cases of stent thrombosis (0% vs. 3.9%), 51% risk reduction in TLR (12.4% vs. 24.%), and a 49% risk reduction in TV-MI (6.4% vs. 12.3%).
"You need careful vessel preparation, intravascular imaging, and then finally the delivery of drug. But it's something ... that almost everybody in any center will be able to do, as opposed to some of these devices like atherectomy, laser, potentially other devices which haven't been demonstrated in a conclusive way to be beneficial and also are more challenging to deliver and deploy," Yeh said.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com