Narrative Review on “Sirolimus-Coated Balloons in Complex Percutaneous Coronary Intervention: Potential Implications for Chronic Total Occlusion Bifurcations”

Syed Sardar Shah; Safa Amin; Attiq Ur Rehman; Zulkifal

doi:10.53941/ti.2026.100017

Abstract

Chronic total occlusions (CTOs) situated at or immediately adjacent to a coronary bifurcation represent one of the most technically and biologically demanding substrates encountered in percutaneous coronary intervention (PCI). The conventional “full metal jacket” strategy multiple, often overlapping drug-eluting stents carries a durable burden of stent thrombosis, neoatherosclerosis, side-branch jailing, and prolonged dual antiplatelet therapy (DAPT). This narrative review appraises the translational rationale for nanomaterial-engineered sirolimus-coated balloons (SCBs) as a metal-minimising strategy in complex percutaneous coronary intervention (PCI), with particular attention to the nanocarrier engineering that renders pharmacologically adequate sirolimus delivery achievable, and to its potential implications for the anatomically hostile CTO-bifurcation setting. The evidence base summarised here is predominantly observational and was not generated from a cohort specifically defined by CTO-bifurcation anatomy. Mechanistic, procedural, and registry-level evidence is synthesised, with emphasis on the phospholipid Nano carrier and crystalline matrix platforms that overcome sirolimus’s comparatively modest lipophilicity relative to paclitaxel, thereby enabling near-instantaneous endothelial transfer and sustained antiproliferative elution—the bench-to-bedside translation that underpins the clinical data reviewed here. Across the FASICO, SIROOP, EASTBOURNE, and ERCTO registries, SCB-based strategies achieved procedural success rates of 96–100%, a 12-month major adverse cardiac event (MACE) rate as low as 4.3%, and a 2-year target lesion revascularisation (TLR) rate of 9% in large-vessel disease. Propensity-matched ERCTO data additionally demonstrated significantly shorter total stent length (44.2 mm vs. 58.1 mm) and a lower pericardial tamponade rate (0.1% vs. 0.4%) when a selective drug-coated balloon (DCB) strategy was employed. None of these four registries enrolled a dedicated, prospectively defined cohort of CTO bifurcation lesions; each captured broader complex-PCI or CTO-PCI populations in which bifurcation anatomy was represented but not separately analysed, and the figures above should therefore be read as indirect, overlapping-subset evidence rather than bifurcation-specific data. Phospholipid nanocarrier-based sirolimus delivery offers a biologically plausible route to effective antirestenotic therapy with substantially reduced permanent metallic scaffolding, and the indirect clinical signal reviewed here is consistent with that rationale, but it does not yet constitute direct proof of benefit in CTO bifurcations specifically. Randomised confirmation from the TRANSFORM-II trial, together with dedicated bifurcation-specific data, is required before this nanomedicine platform can be regarded as a default strategy in this setting.

References

1.
Sianos, G.; Morel, M.A.; Kappetein, A.P.; et al. The SYNTAX Score: An angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005, 1, 219–227.
2.
Galassi, A.R.; Sianos, G.; Werner, G.S.; et al. Retrograde recanalization of chronic total occlusions in Europe: Procedural, in-hospital, and long-term outcomes from the multicenter ERCTO registry. J. Am. Coll. Cardiol. 2015, 65, 2388–2400.
3.
Lunardi, M.; Louvard, Y.; Lefèvre, T.; et al. Definitions and standardized endpoints for treatment of coronary bifurcations. J. Am. Coll. Cardiol. 2022, 80, 63–88.
4.
Lawton, J.S.; Tamis-Holland, J.E.; Bangalore, S.; et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022, 145, e18–e114. https://doi.org/10.1161/CIR.0000000000001038.
5.
Jeger, R.V.; Farah, A.; Ohlow, M.A.; et al. Drug-coated balloons for small coronary artery disease (BASKET-SMALL 2): An open-label randomised non-inferiority trial. Lancet 2018, 392, 849–856.
6.
Zhao, L.; Feng, L.; Shan, R.; et al. Nanoparticle-based approaches for treating restenosis after vascular injury. Front. Pharmacol. 2024, 15, 1427651.
7.
Poon, M.; Marx, S.O.; Gallo, R.; et al. Rapamycin inhibits vascular smooth muscle cell migration. J. Clin. Investig. 1996, 98, 2277–2283.
8.
Madanchi, M.; Attinger-Toller, A.; Gjergjizi, V.; et al. Treatment of coronary lesions with a novel crystalline sirolimus-coated balloon. Front. Cardiovasc. Med. 2024, 11, 1316580.
9.
Cortese, B.; Di Palma, G.; Latini, R.A.; et al. Immediate and short-term performance of a novel sirolimus-coated balloon during complex percutaneous coronary interventions: The FAtebenefratelli SIrolimus COated-balloon (FASICO) registry. Cardiovasc. Revasc. Med. 2017, 18, 487–491.
10.
Ciardetti, N.; Mattesini, A.; Werner, G.S.; et al. Drug-coated balloons in the European Registry of Chronic Total Occlusion: The ERCTO Registry. JACC: Cardiovasc. Interv. 2025, 18, 2209–2221.
11.
Truesdell, A.G.; Alasnag, M.A.; Kaul, P.; et al. Intravascular imaging during percutaneous coronary intervention: JACC state-of-the-art review. J. Am. Coll. Cardiol. 2023, 81, 590–605.
12.
Hill, J.M.; Kereiakes, D.J.; Shlofmitz, R.A.; et al. Intravascular lithotripsy for treatment of severely calcified coronary artery disease. J. Am. Coll. Cardiol. 2020, 76, 2635–2646.
13.
Sciahbasi, A.; Salvi, N.; Heang, T.M.; et al. Long term clinical outcome of sirolimus drug coated balloons in large coronary vessels. Catheter. Cardiovasc. Interv. 2024, 103, 532–538.
14.
Rocchetti, M.; Tua, L.; Cereda, A.; et al. Drug-Coated Balloons Versus Non-Coated Balloons for Side Branch Treatment in Bifurcation Lesions: A Systematic Review and Meta-Analysis. Catheter. Cardiovasc. Interv. 2025, 106, 530–539.
15.
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, 1–15.
16.
Greco, A.; Sciahbasi, A.; Abizaid, A.; et al. Sirolimus-coated balloon versus everolimus-eluting stent in de novo coronary artery disease: Rationale and design of the TRANSFORM II randomised clinical trial. Catheter. Cardiovasc. Interv. 2022, 100, 544–552.

Scilight Press

Author Information

Abstract

Keywords

References

About Scilight

Journals

Publishing Policies

Contact Us