A paclitaxel-coated balloon, Agent DCB (Boston Scientific), was superior to an uncoated balloon for treating coronary in-stent restenosis in patients undergoing percutaneous coronary intervention (PCI), in results released following the balloon’s recent approval by the US Food and Drug Administration (FDA).

Agent DCB received breakthrough device designation in 2021 and was approved by the FDA in part on the basis of the results of a prespecified analysis of the pivotal trial, presented at the Transcatheter Cardiovascular Therapeutics 2023 Congress.

This paper provides details of that trial, in which the primary endpoint of 1-year target lesion failure occurred in 17.9% of the paclitaxel-coated balloon group vs 28.6% of the uncoated balloon group, meeting criteria for superiority (hazard ratio [HR], 0.59).

These final results were presented at the Cardiovascular Research Technologies meeting and published online on March 9 in JAMA.

“It’ll be very important for cardiologists to be meticulous in applying best practices for treating in-stent restenosis lesions prior to using a drug-coated balloon,” lead author Robert W. Yeh, MD, MSc, of Beth Israel Deaconess Medical Center in Boston, Massachusetts, told theheart.org | Medscape Cardiology.

Understanding why a stent might have failed the first time “in nearly all cases will require some form of intravascular imaging,” he said. A drug-coated balloon should be applied “only after using the right tools to ensure that the old stent is adequately expanded, and [that] things like vessel calcification have been adequately addressed.”

Target Lesion Failure Rates Lower

Researchers conducted a US multicenter randomized clinical trial that included 600 patients with in-stent restenosis. The mean age was 68 years; 26.2% were women; 7% were Black; and 6% were Hispanic.

Patients had a visually estimated reference vessel diameter > 2.0-4.0 mm, a lesion length < 26 mm, and a target lesion diameter stenosis of less than 100% but greater than 50% (symptomatic patients) or greater than 70% (asymptomatic patients).

Four hundred and six patients underwent treatment with a paclitaxel-coated balloon and 194 with an uncoated balloon (2:1 randomization).

The primary endpoint of 1-year target lesion failure — defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death — occurred in 17.9% of those in the paclitaxel-coated balloon group vs 28.6% of those in the uncoated balloon group, meeting the criteria for superiority (HR, 0.59).

Target lesion revascularization and target vessel-related myocardial infarction occurred less frequently among patients treated with the coated balloon: 13.0% vs 4.7% (HR, 0.50) and 5.8% vs 11.1% (HR, 0.51), respectively.

In contrast, the rate of cardiac death was 2.9% vs 1.6% (HR, 1.75) in the coated vs uncoated balloon groups, respectively.

No definite or probable stent thrombosis occurred in any patient at 1 year in the coated balloon group vs six patients in the uncoated balloon group. Quality-of-life outcomes were similar between the groups.

Subgroup analyses showed that among patients with multiple stent layers, the rate of target lesion failure was 23.8% in the coated balloon group vs 40.0% in the uncoated balloon group (HR, 0.55). Among patients with diabetes, the rates of target lesion failure were 21.6% vs 29.2%, respectively (HR, 0.71).

Intracoronary Imaging Rates Higher

“This isn’t a therapy that is meant to be applied in all cases and every patient,” Yeh said. “We know that drug-eluting stents are still very effective in treating coronary blockages, and many patients with stable coronary disease can be treated adequately with medications alone. How these balloons perform in other potential situations where cardiologists might prefer to avoid stents, including bifurcations, long lesions, or small vessels, will be important areas of future research.”

Mirvat Alasnag, MD, a member of the American College of Cardiology Interventional Council, commented on the study for theheart.org | Medscape Cardiology. “This AGENT IDE trial complements the 10-year results of the ISAR-DESIRE 3 trial that once again noted fewer events and repeat revascularizations with drug-coated balloons in patients with in-stent restenosis,” she said.

“Since patients with long disease, severe stenosis, and multiple layers of stents were included, this makes the option of drug-coated balloons in real-life practice an attractive strategy with a high safety record,” she noted.

“Perhaps interventional cardiologists should diagnose the mechanism of stent failure with intracoronary imaging (which was high in this study compared with real-world practices) to appropriately size the balloon and avoid flow-limiting dissections,” Alasnag added. “It would also permit the diagnosis of under-expanded stents and calcified neointimal hyperplasia, or neoatherosclerosis, that would require the use of other plaque-modifying tools such as atherectomy or cutting balloons.”

In addition, she said, “It would be important to understand the efficacy of drug-coated balloons according to the underlying pathology, especially in those with previously undersized stents, a geographic miss, bifurcations, and small-caliber vessels.”

Like Alasnag, Amartya Kundu, MD, and David J. Moliterno, MD, both of the University of Kentucky, Lexington, Kentucky, wrote in a related editorial that the use of intravascular imaging in the study was higher (“five to 10 times”) than what usually occurs in practice in the United States, which may have influenced outcomes. They also noted that using noncoated balloons as the study control “does not represent the standard of care for treating in-stent restenosis in current practice.”

More than half of the patients in the trial underwent interventions for stable angina, where PCI is of questionable benefit, they added. Furthermore, the additional financial costs of drug-coated balloons, as well as the intravascular imaging, need to be taken into consideration.

Nevertheless, they concluded, “AGENT IDE provides strong evidence for regulatory approval of coronary DCB in the US, potentially providing numerous patients access to this established technology.”