Treatment of In-Stent Restenosis in Small Vessels with Paclitaxel-Coated Balloons

Coronary artery disease (CAD) in smaller epicardial vessels occurs in 30% to 67% of patients undergoing percutaneous coronary intervention and poses particular technical challenges. Small vessels (SVs), usually defined as those with diameters <2.25 to 3.0 mm, account for a higher risk of in-stent restenosis (ISR), which translates into higher rates of target lesion revascularization (TLR). In addition, ISR treatment often relies on optimizing the previous stent and implanting a new device. However, placing a second stent layer reduces luminal gain, a particularly relevant issue in SVs. Consequently, not only do these vessels carry a greater risk of ISR, but they also result in worse clinical outcomes when it occurs.

Drug-coated balloons (DCBs) have emerged as a promising alternative for treating ISR because they allow for the delivery of an antiproliferative agent while avoiding a new metal implant. However, the available evidence supporting their use in this context is still limited.

The aim of this study was to assess the efficacy and safety of DCBs compared with conventional balloon angioplasty, considering treated vessel size.

The primary endpoint (PEP) was the 1-year rate of target lesion failure (TLF), defined as a composite of myocardial infarction related to the treated vessel, ischemia-driven target lesion revascularization, or cardiac death.

The AGENT IDE trial (Clinical Trial to Evaluate the Paclitaxel-Coated Balloon Catheter for the Treatment of In-Stent Restenosis) randomized 600 patients with ISR to treatment with a DCB or with conventional balloons (2:1 ratio). This prespecified analysis examined the effect of treatment according to reference vessel diameter (RVD): ≤2.75 mm for small vessels and >2.75 mm for large vessels.

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Among the 597 patients with known RVD, 56% had SVs (mean RVD: 2.4±0.3 mm) and 44% had large vessels (mean RVD: 3.1±0.3 mm). The 1-year TLF rate was 20.6% in SVs and 22.6% in large vessels (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.65–1.31; p = 0.65). Regarding treatment, DCBs were associated with a 39-% relative reduction in TLF compared with balloon angioplasty in SVs (17.7% vs. 27.4%; HR: 0.61; 95% CI: 0.37–0.99), and with a 43-% reduction in large vessels (18.4% vs. 30.5%; HR: 0.57; 95% CI: 0.34–0.96). The benefits of DCBs were consistent regardless of vessel size (p for interaction = 0.88). There were no cases of definite or probable stent thrombosis reported among patients treated with DCBs.

Conclusion

This prespecified subgroup analysis of the AGENT IDE trial showed that patients with lesions ≤2.75 mm treated with DCBs had a significantly lower incidence of TLF and TLR at 1 year compared with those treated with conventional balloons. It is important to highlight that DCB angioplasty consistently showed a reduction in 1-year clinical events, regardless of vessel size. Overall, DCBs are an effective therapeutic option for patients with coronary in-stent restenosis.

Original Title: Paclitaxel-Coated Balloon for the Treatment of Small Vessel In-Stent Restenosis A Subgroup Analysis of the AGENT IDE Randomized Trial.

Reference: Jason Wen, MD et al JACC Cardiovasc Interv. 2025;18:2701–2710.