Coronary bifurcation lesions are treated in 15-20% of all percutaneous coronary intervention (PCI) cases and are a challenging scenario.¹ Drug-eluting stents (DES) and better bifurcation PCI techniques improve the treatment of bifurcations beyond bare-metal stents, but stent thrombosis (ST) and in-stent restenosis (ISR) remain threats. Although the provisional technique remains the default approach, more complex two-stent techniques are contemplated in some cases that carry the risk of side-branch (SB) restenosis. Drug-coated balloons (DCB) are appealing in a KISSS (keep it swift, simple, and safe) strategy for a simpler procedure. Coronary artery bifurcations sometimes have significant size mismatch between the proximal and distal main branch (MB), which may increase the incidence of ISR and potentially impact SB coronary flow dynamics.¹ DCB might represent an alternative to plain old balloon angioplasty (POBA) and/or DES for SB-PCI because it maintains the bifurcation anatomy, particularly in the carina area, ensuring even distribution of high-dose antiproliferative drugs across the entire blood vessel surface, avoiding stent fracture/malapposition from the addition of another stent in the SB, and avoiding complex steps such as rewiring or reballooning.¹ DCB precludes additional stent implantation and circumvents the risk of stent malapposition/fracture, and therefore may decrease ISR and ST.

The use of DCB in the SB, in contrast to any of the two-stent techniques, eliminates the possibility of incomplete coverage of the bifurcation area, scaffolding of SB ostium, stent distortions in MB through the SB access, and overlapping and crushing of multiple metal layers. Additionally, DCB may be superior to POBA in terms of plaque stabilization and vascular remodeling. Two recent meta-analyses comparing DCB with POBA for SB treatment found that DCB were associated with significantly lower late lumen loss (LLL) and a reduced incidence of major adverse cardiac events (MACE).^2,3 However, no differences were found when analyzing the individual components of MACE. The DCB-BIF (Comparison of Noncompliant Balloon With Drug-Coated Balloon Angioplasties for Side Branch After Provisional Stenting for Patients With True Coronary Bifurcation Lesions) randomized controlled trial (RCT) results showed that, in true coronary bifurcation lesions undergoing provisional MB stenting combined with a DCB for the compromised SB, there was a lower 1-year composite outcome compared with POBA.⁴ When a DCB is used in the MB, there is a significant increase in the ostial SB area at follow-up. This phenomenon is likely to reduce the high rates of SB-ISR.¹ In a retrospective, single-arm study, Ikuta et al. found that DCB treatment of the SB was associated with late lumen gain in 71.7% of cases, which had lower MACE and target-lesion revascularization rates than did those with LLL.⁵ Despite these promising data, there are still issues to be clarified with the technique of DES in MB and DCB in the SB because predilatation of the SB can lead to dissection and increase the likelihood of bailout stenting and advancing the DCB after provisional stent of the MB can be difficult due to lower flexibility and a larger balloon profile.

The evidence indicates that a hybrid strategy combining DCB and DES for left main coronary artery bifurcation lesions can lead to better outcomes than DES alone (provisional stenting or two-stent strategies), particularly by reducing LLL and target-lesion failure at 1 and 2 years, respectively, as demonstrated in the results of one observational study.⁶ Liu et al. demonstrated in another observational study that a hybrid strategy using a DCB in the SB in addition to a DES in the MB was superior to a two-stent strategy in terms of LLL, both at the SB ostium and at the proximal MB.⁷ The effectiveness of DCB depends on drug transfer, bioavailability, and drug transit time, which is subject to proper lesion preparation. The initial step involves predilating the MB and/or SB using conventional balloons with an inflation pressure higher than nominal and a balloon-to-artery ratio of 1.0 (Figure 1).

Figure 1: DCB Treatment Approach for Coronary Bifurcation Lesion

Adapted with permission from Her AY, Ahmad WAW, Bang LH, et al. Drug-coated balloons-based intervention for coronary artery disease: the second report of Asia-Pacific Consensus Group. JACC Asia. 2025;5(6):701-717. doi:10.1016/j.jacasi.2025.02.017
DCB = drug-coated balloon; DES = drug-eluting stent; MB = main branch; NCB = noncompliant balloon; SB = side branch.

Manipulation of the DCB must be avoided during preparation of the device. DCB application to the SB is feasible if no flow-limiting dissection occurs and residual stenosis is ≤30% in the MB and ≤70% in the SB with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, using a DCB-to-artery ratio of 1.0 for a minimum of 60 sec. The DCB should extend 4-5 mm into the MB and 2-3 mm distally beyond the predilated area. Subsequently, DCB can be similarly applied to the MB, extending the balloon-covered length 2-3 mm beyond both sides of the predilated area. However, in cases of suboptimal lesion preparation, if the result remains unsatisfactory despite additional lesion preparation, deploying a DES in the MB and performing provisional stenting in the SB may be contemplated (Figure 1).⁸ Techniques for DCB in bifurcations have been evaluated in various studies. DCB in the SB, as demonstrated in the DCB-BIF trial, typically follows a provisional stenting approach in the MB.⁴ Complete DCB with sequential DCB in the SB then MB and no final kissing is being evaluated in the EBC DCB (The European Bifurcation Club Randomized Trial of Stepwise Provisional Stenting Versus Drug Coated Balloon Therapy for Non-left Main True Coronary Bifurcations) randomized noninferiority trial.⁹ The proximal optimization technique (POT)–side-DCB-POT, in line with the recommendation of the European Bifurcation Club (ECB), consists of a sequential approach to bifurcation stenting using the provisional strategy. This strategy is easy to perform and respects the geometry of all three bifurcation segments.¹ As an alternative, using a DCB-alone strategy in the SB and a DES in the MB may be considered reasonable.

In conclusion, this novel stentless technology might improve the short- and long-term outcome of bifurcation lesions, allowing limited or no use of a permanent metal device. However, larger, adequately powered RCTs are warranted to further validate the role of DCB in such lesions.

References

1. Dash D, Mody R, Ahmed N, Malan SR, Mody B. Drug-coated balloon in the treatment of coronary bifurcation lesions: a hope or hype?. Indian Heart J. 2022;74(6):450-457. doi:10.1016/j.ihj.2022.10.193
2. Corballis NH, Paddock S, Gunawardena T, Merinopoulos I, Vassiliou VS, Eccleshall SC. Drug coated balloons for coronary artery bifurcation lesions: a systematic review and focused meta-analysis. PLoS One. 2021;16(7):e0251986. Published 2021 Jul 9. doi:10.1371/journal.pone.0251986
3. Zheng Y, Li J, Wang L, et al. Effect of drug-coated balloon in side branch protection for de novo coronary bifurcation lesions: a systematic review and meta-analysis. Front Cardiovasc Med. 2021;8:758560. Published 2021 Dec 14. doi:10.3389/fcvm.2021.758560
4. Gao X, Tian N, Kan J, et al. Drug-coated balloon angioplasty of the side branch during provisional stenting: the multicenter randomized DCB-BIF trial. J Am Coll Cardiol. 2025;85(1):1-15. doi:10.1016/j.jacc.2024.08.067
5. Ikuta A, Kubo S, Ohya M, et al. Impact of late lumen loss on clinical outcomes of side-branch bifurcation lesions treated by drug-coated balloon angioplasty with main-branch stenting. Cardiovasc Revasc Med. 2022;41:92-98. doi:10.1016/j.carrev.2021.12.020
6. Pan L, Lu W, Han Z, et al. Drug-coated balloon in the treatment of coronary left main true bifurcation lesion: a patient-level propensity-matched analysis. Front Cardiovasc Med. 2022;9:1028007. Published 2022 Nov 3. doi:10.3389/fcvm.2022.1028007
7. Liu H, Tao H, Han X, et al. Improved Outcomes of combined main branch stenting and side branch drug-coated balloon versus two-stent strategy in patients with left main bifurcation lesions. J Interv Cardiol. 2022;2022:8250057. Published 2022 Jan 11. doi:10.1155/2022/8250057
8. Her AY, Ahmad WAW, Bang LH, et al. Drug-coated balloons-based intervention for coronary artery disease: the second report of Asia-Pacific Consensus Group. JACC Asia. 2025;5(6):701-717. doi:10.1016/j.jacasi.2025.02.017
9. Ceric Sàrl. The European Bifurcation Club Randomized Trial of Stepwise Provisional Stenting Versus Drug Coated Balloon Therapy for Non-left Main True Coronary Bifurcations (EBC DCB) (ClinicalTrials.gov website). 2025. Available at: https://clinicaltrials.gov/study/NCT06822322. Accessed 12/16/2025.