FDA Approves Coronary Drug-Coated Balloon Specifically for In-Stent Restenosis
This trial randomized 600 U.S. patients with restenosis of a previously placed stent 2:1 to treatment with the AGENT drug-coated balloon or with regular balloon angioplasty. Target lesion failure at one year was significantly lower with the drug-coated balloon, as were target vessel myocardial infarction and stent thrombosis.
This is a summarized version of the full in-depth article on Relias Media.
By Jeffrey Zimmet, MD, PhD. Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center.
In-Stent Restenosis: A Persistent Challenge in Coronary Intervention
In-stent restenosis (ISR) remains a significant issue despite advancements in drug-eluting stents (DES), with ISR requiring intervention in an estimated 10% of all percutaneous coronary interventions (PCIs). Traditionally, the placement of an additional DES is the most common approach for treating ISR, offering better outcomes than plain balloon angioplasty alone. However, adding more layers of metal stents into the artery introduces complexities, such as the risk of target lesion failure and recurrent restenosis. As a result, interest in alternative treatments like drug-coated balloons (DCB) has grown. These devices deliver antiproliferative drugs to the arterial wall without the need for additional stent layers, potentially simplifying the treatment of ISR.
The AGENT IDE Trial: A Breakthrough in DCB Use for ISR
The AGENT IDE trial was a prospective, randomized controlled trial designed to evaluate the efficacy and safety of a commercially available DCB for the treatment of ISR lesions. Conducted at 40 U.S. sites, the trial enrolled 600 patients, who were randomized 2:1 to receive either DCB or plain balloon angioplasty following successful lesion pre-dilation. Initial data from 480 patients (321 in the DCB group, 159 in the balloon angioplasty group) were presented in October 2023, and the results were subsequently reviewed by the U.S. Food and Drug Administration (FDA).
The primary endpoint was one-year target lesion failure, defined as a composite of target lesion revascularization, myocardial infarction (MI), or cardiac death. Results demonstrated the superiority of DCB over balloon angioplasty, with a significantly lower incidence of target lesion failure in the DCB group (17.9% vs. 28.7%; P = 0.0063). This represents a 38% relative risk reduction.
Some individual components of the primary endpoint were also significantly improved in the DCB group:
- Target lesion revascularization was reduced by 51% (12.4% vs. 24.0%; P = 0.002).
- Target vessel MI was reduced by 49% (6.4% vs. 12.3%; P = 0.03).
- Stent thrombosis occurred in 3.9% of the balloon angioplasty group but was completely absent in the DCB group.
These results led the FDA to approve the use of this coronary DCB on March 1, 2024, marking the first approval of a coronary DCB in the United States.
Clinical Significance of the AGENT IDE Trial
The AGENT IDE trial is notable for being the largest trial to evaluate DCB for ISR, with results demonstrating a clear advantage over balloon angioplasty. Previous trials, such as the PACCOCATH ISR and PEPCAD trials, have shown similar efficacy for DCB, particularly in Europe, where the European Society of Cardiology recommended DCB for ISR with a Class IA recommendation in 2014. However, these earlier trials were smaller in scale, and DCB use in the United States had remained limited due to insufficient data for FDA approval.
One critique of the AGENT IDE trial is the choice of balloon angioplasty as the comparator, as 85% of ISR cases in the United States are typically treated with repeat stenting. Nonetheless, the AGENT trial provides strong evidence supporting DCB use, offering a non-stent-based alternative for ISR treatment that avoids the complications associated with placing additional metal layers in already-stented arteries.
Remaining Challenges and Future Directions
Despite the advantages of DCB demonstrated in the AGENT trial, the results also underscore the complexity of treating ISR. The target lesion failure rate of 17.9% in the DCB group remains relatively high, reflecting the ongoing challenge of effectively managing restenotic lesions. This highlights the importance of continuous innovation in stent technology, lesion preparation techniques, and the use of intravascular imaging to optimize outcomes.
While the AGENT trial establishes DCB as an effective and safe option for ISR, questions remain about its broader application, particularly in treating de novo coronary lesions. Currently, DCB use is mostly limited to ISR, but ongoing and future trials may help determine whether DCB can be a viable treatment for other types of coronary artery disease. Additionally, alternatives such as intracoronary radiation (brachytherapy), while effective in some cases, remain niche therapies and are not widely available.
Conclusion
The approval of the first coronary DCB in the United States, based on the results of the AGENT IDE trial, marks a significant advancement in the treatment of in-stent restenosis. The trial demonstrated the superiority of DCB over balloon angioplasty in reducing key clinical outcomes, including target lesion revascularization, MI, and stent thrombosis. While DCB is not a panacea for ISR, it offers a promising alternative to additional stent placement and represents a critical tool in the ongoing effort to improve outcomes for patients undergoing PCI. Further research is needed to explore the potential of DCB in other areas of coronary intervention, but the AGENT trial sets a new standard for ISR treatment in the United States.
Read the full in-depth article on Relias Media
We discuss the drug-coated balloon specifically for in-stent restenosis in more detail in our full write-up on Relias Media.