UPMC Heart and Vascular Institute’s Experience with the AGENT™ Drug-Coated Balloon for In-Stent Restenosis

In-stent restenosis (ISR) remains a persistent challenge in the treatment of coronary artery disease (CAD). For years, one of the primary solutions to dealing with ISR, when feasible, has been to place additional stents within failing stents. However, this strategy can lead to complications such as increased metal burden and higher long-term risk of restenosis, and other complications.

The UPMC Heart and Vascular Institute’s interventional cardiology teams have been at the forefront of addressing this issue, leveraging the recently FDA-approved AGENT™ Drug-Coated Balloon (DCB) as an alternative approach to ISR in well-selected patients.

William Bachinsky, MD, FACC, FSCAI, an interventional cardiologist at the UPMC Heart and Vascular Institute in Central Pennsylvania was the site principal investigator for the AGENT investigational device exemption trial that began in 2021, and has been directly involved in the evaluation and adoption of this new approach to ISR. Dr. Bachinsky was for two decades the director of Interventional Cardiology and director of Cardiovascular Research before stepping down from those roles in 2024, though he continues his interventional cardiology clinical practice and research.

"We were part of the original clinical trials for AGENT DCB and performed the first case in the United States in 2021 during that trial,” says Dr. Bachinsky. “Since then, we have gained extensive experience using the device, treating approximately 50 patients before its ultimate FDA approval.”

Collaborating with Dr. Bachinsky during the initial AGENT DCB trial was Anay Pradhan, MD, FACC, FSCAI, director of the Complex Higher-Risk Intervention Program at the UPMC Heart and Vascular Institute in Central Pa.

From Clinical Trials to FDA Approval

Drug-coated balloons have been used to treat peripheral artery disease (PAD) for more than a decade as a way to avoid placing stents in the femoral (leg) arteries, among other indications. The efficacy of DCBs in these cases led to the idea that they could also be effective in treating coronary ISR. However, coronary arteries are more prone to complications, often requiring stents to maintain vessel patency.

The AGENT DCB device was designed specifically for coronary artery ISR, delivering paclitaxel, an antiproliferative drug, directly to the arterial wall. Unlike repeat stenting, this approach does not leave additional metal behind, which can reduce the risk of further restenosis and late stent thrombosis.

"This device gives us another option for ISR that does not require placing more metal in an already stented artery," says Dr. Bachinsky. "For the right patient, it can help us restore blood flow while preserving future treatment options.”

Following the IDE trial, the AGENT DCB device received FDA and CMS approval in 2023, allowing for its broader adoption into clinical practice. 

Having already been involved in the clinical trial, the UPMC Heart and Vascular Institute was among the first centers in the country to use the device post-approval.

Identifying the Right Patient Population 

ISR occurs in about 10-15% of patients with coronary artery stents. Some patients are at higher risk for ISR, including individuals with diabetes and patients with highly calcified or long-segment lesions that are more difficult-to-treat with stents.

“As a whole, women are more prone to ISR than are men, largely due to their innate anatomy – often with smaller coronary arteries, comparatively- speaking – which makes them more susceptible,” says Dr. Bachinsky.

While AGENT DCB has been shown to be highly efficacious in treating ISR cases, some patients may still require alternative approaches.

Severe ISR cases with complex anatomy may be better treated with bypass surgery, while others may do well with medical therapy alone.

“AGENT DCB is not a panacea for ISR in the coronary arteries,” says Dr. Bachinsky. “We have to evaluate each patient carefully and tailor the treatment or select the cases that will receive maximum benefit from this approach. It won’t be an option in every case of ISR.”

How AGENT DCB Works

The AGENT DCB device follows standard catheter-based techniques. The artery is first prepared using intravascular imaging and techniques such as intravascular lithotripsy to break up existing calcium deposits and ensure optimal expansion of the existing stent.

"An important factor in making AGENT DCB successful is properly preparing the artery before delivering the drug," says Dr. Bachinsky. "If the original stent is not fully expanded, which in and of itself is a common cause of ISR, the risk of repeat restenosis is much higher. Our approach to patient evaluation and planning for use of the device is meticulous to make sure we get the best possible result."

The drug-coated balloon is then inflated inside the stent for a brief period, delivering paclitaxel to the arterial wall before being removed. This method treats the restenosis, avoids adding another layer into the vessel, and generally preserves future therapeutic options that can be compromised by the presence of layered stents.

Benefits for Patients

By avoiding the need for additional stents, AGENT DCB offers several advantages for patients and for clinical teams.

“We can achieve a lower risk of late-stent thrombosis, which is something we are always cognizant of with multiple stent layers because of the potential catastrophic outcomes that can occur,” says Dr. Bachinsky. “And, again, we can better preserve future treatment options without the additional layers of metal inside an artery. Of course, AGENT DCB is a minimally invasive PCI approach, which has benefits, and the risk of recurrent ISR is comparable to other approaches.”

Not Every Hospital Can Use AGENT DCB

While AGENT DCB has the potential to significantly transform how ISR treatment is handled in many patients, not all hospitals or interventional cardiologists are permitted to use it. Boston Scientific, the device's manufacturer, has placed strict controls on which hospitals have access, ensuring that only centers with the appropriate expertise and infrastructure are performing the procedure.

"This is not a device that can just be used anywhere," says Dr. Bachinsky. "The manufacturer has been highly selective in where it is deployed. The UPMC Heart and Vascular Institute in Central Pa. was chosen because of our experience in ISR management and our ability to achieve excellent outcomes for patients. Having the right skill set and the ability to use advanced imaging and calcium modification techniques are essential."

This controlled access to the device highlights the leading role that the UPMC Heart and Vascular Institute plays nationally in interventional cardiology and the ability to offer patients state-of-the-art treatment options that may not be available elsewhere.

What Referring Physicians Should Know About ISR and AGENT DCB

For referring physicians, recognizing ISR and understanding available treatment options is key to optimal patient management and outcomes. AGENT DCB can be a great option for patients with ISR, particularly those who are not ideal candidates for additional stenting.

"In most cases, ISR does not require immediate emergency intervention," says Dr. Bachinsky. "This gives us and our patients the luxury of more time to consider the options, their goals of care, and appropriately evaluate them to see if AGENT DCB makes sense. However, for those who qualify, AGENT DCB provides an effective and minimally invasive solution for their coronary ISR."

What Does the Future of Drug-Coated Balloons Look Like?

According to Dr. Bachinsky, looking ahead, there is growing interest in expanding the use of DCBs beyond ISR – specifically to de novo lesions or blockages in the coronary arteries.