Hybrid Percutaneous Coronary Intervention Combining a Bioresorbable Scaffold With Drug-coated Balloons Versus a Conventional Drug-eluting Stent-based Strategy in Patients With Long and Diffuse Coronary Artery Disease

1. Newer-generation drug-eluting stents for the treatment of de novo coronary artery disease Among patients with significant coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), the use of newer-generation drug-eluting stents (DES) is currently recommended in all patients and lesions subsets. However, despite modern iterations in DES designs including reduced stent strut thickness, improved polymer biocompatibility and/or resorption, and controlled antiproliferative drug release, long-term clinical outcomes after PCI in patients with CAD are not further improving. In a patient-level pooled analysis of 19 prospective randomized controlled trials including 25,032 patients undergoing PCI, of which 13,380 underwent PCI with second-generation DES, very-late stent-related events occurred between 1 and 5 years after PCI at a rate of ∼2%/year with all stent types, with no plateau evident, highlighting the need for new approaches to improve long-term outcomes after PCI. Among potential responsible mechanisms, the persistence of a metallic stent platform and a permanent polymer coating prevents vasomotion and positive coronary artery remodelling, and triggers inflammation, neoatherosclerosis and stent fracture which may lead to in-stent restenosis or very late stent thrombosis. These findings highlight the need for novel iterations of DES technologies and innovative PCI approaches to overcome the persisting limitations of current generation DES for the treatment of patients with CAD. 2. Percutaneous coronary intervention for de novo long and/or diffuse coronary artery disease Patients with de novo long and/or diffuse CAD undergoing PCI represent a particularly challenging clinical subset and remain an unmet clinical need for the interventional community. De novo long and/or diffuse coronary lesions are found in 20% of patients undergoing PCI and newer-generation DES implantation in patients with long and/or diffuse CAD is associated with an increased risk of stent failure at long-term follow-up. In a patient-level pooled analysis from the GRAND-DES registry including 9,217 patients from five Korean multicenter DES registries, 1,182 patients (13%) underwent long stenting (\>40 mm) with contemporary second-generation DES. At a median follow-up duration of 2 years, long stenting was associated with significantly higher rates of target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization (8.1% vs. 4.5%, IPTW adjusted HR 1.88, 95% CI: 1.67-2.13; p\<0.001), and definite or probable stent thrombosis (1.0% vs. 0.4%, IPTW adjusted HR 2.20, 95% CI: 1.51-3.20; p\<0.001) compared with shorter stenting (≤40 mm). Target vessel failure (TVF), defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target vessel revascularization, at 2 years were 10.8% vs. 6.0% in the long and short stenting groups, respectively. Diffuse long lesions commonly require stenting with long (≥ 60 mm) overlapping DES, which is a known predictor of adverse events such as in-stent restenosis or stent thrombosis. Furthermore, particularly for young patients with long and/or diffuse coronary lesions, the 'full metal jacket' with metallic DESs may preclude the possibility of future surgical revascularization options. 3. Hybrid percutaneous coronary intervention for de novo long and/or diffuse coronary artery disease Given the recent data supporting the safety and efficacy of a drug-coated balloon (DCB)-only strategy in patients with small vessel CAD in addition to the natural step-down of vessel diameter in de novo long and/or diffuse coronary lesions, a hybrid PCI approach combining a newer-generation DES (implanted at the larger, more proximal, segment of the lesion) and a DCB (located at the smaller, more distal segment of the lesion) has been recently proposed as a potential alternative treatment strategy for patients with de novo long and/or diffuse coronary artery disease. Hybrid PCI using a single DES combined with DCB instead of several overlapping DES may reduce total stent length, thus minimizing the risk of long-term stent failure. In the prospective, multicenter, observational, non-randomized HYPER study including 106 consecutive patients with de novo diffuse CAD undergoing PCI with a hybrid approach, consisting in the combined use of DES and DCB in contiguous coronary segments, procedural success was 96.2%, and the primary device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction and ischemia-driven target lesion revascularization at one year of follow-up was 3.7%, with all the adverse events caused by ischemia-driven target lesion revascularization. Similarly, a previous retrospective study demonstrated that a DCB-only strategy or in combination with DES (hybrid approach) in the treatment of de-novo diffuse CAD (\>25 mm), had comparable rates of major adverse cardiovascular events (20.8% vs. 22.7%; p=0.74) and target lesion revascularization (9.6% vs. 9.3%, p=0.84), respectively at 2 years follow up. However, the long-term results of a hybrid PCI strategy combining DES with DCB remain limited by the persisting high rates of stent-related adverse outcomes associated with the use of permanent metallic DES. 4. Bioresorbable scaffolds for the treatment of coronary artery disease Bioresorbable scaffolds (BRS) were developed to overcome the persisting limitations of contemporary DES, enabling vessel restoration and reducing long term risk of device failure after PCI. BRS are hypothesized to provide a temporary drug-eluting scaffold, which supports the vessel after implantation, thus limiting acute recoil and negative remodeling, and enabling a natural biologic reconstruction of the arterial wall and restoration of the vascular function once the scaffold is resorbed.

Freesolve (Biotronik AG, Bülach, Switzerland) is a third-generation magnesium-based sirolimus-eluting bioresorbable scaffold that has obtained CE mark for coronary use in 2024. This bioresorbable scaffold is built with a refined magnesium alloy and enhances some scaffold properties, such as radial strength, scaffolding time and marker visibility, broadens the size range and reduces crossing profile and strut thickness with the aim to improve device-related clinical outcomes. In the BIOMAG-I first-in-man study that included 116 patients with 117 coronary artery lesions, in-scaffold late lumen loss was 0.21+/- 0.31 mm at 6 months of follow-up. Intravascular ultrasound assessment showed preservation of the scaffold area (mean 7.59 mm2 \[SD 2.21\] post-procedure vs 6.96 mm2 \[SD 2.48\]) at six months) with a low mean neointimal area (0.02 mm2 \[SD 0.10\]). Optical coherence tomography revealed that struts were embedded in the vessel wall and were already hardly discernible at six months. Target lesion failure occurred in one (0.9%) patient; a clinically driven target lesion revascularization was performed on post-procedure day 166. No definite or probable scaffold thrombosis or myocardial infarction was observed. These findings demontrate that the implantation of Freesolve bioresorbable scaffold (Biotronik AG, Bülach, Switzerland) in de novo coronary lesions is associated with favorable safety and performance outcomes, comparable to contemporary drug-eluting stents. At 12 months of follow-up, after completion of resorption, in-scaffold late lumen loss was 0.24±0.36 mm (median 0.19, interquartile range 0.06-0.36). The minimum lumen area was 4.95±2.24 mm² by intravascular ultrasound and 4.68±2.32 mm² by optical coherence tomography. Three target lesion failures were reported (2.6%, 95% confidence interval: 0.9-7.9), all clinically driven target lesion revascularisations. Cardiac death, target vessel myocardial infarction and definite or probable scaffold thrombosis were absent. These results confirm that this third-generation bioresorbable magnesium scaffold is clinically safe and effective, making it a possible alternative to DES. Potential factors contributing to this difference in clinical outcomes compared to other available bioresorbable scaffolds, include different scaffold design and materials, reduced thrombogenicity, as shown in preclinical animal models shorter resorption time, and the BIOlute active coating as that is also used in the Orsiro (Biotronik AG, Bülach, Switzerland) DES that has demonstrated consistently low rates of target lesion failure in several randomized clinical trials.

With the positive data emerging, a hybrid 'leaving nothing behind' approach combining a BRS with a DCB in de novo long/diffuse coronary artery disease represents a novel promising treatment strategy that may provide additional clinical benefits compared with a hybrid PCI approach combining a DES and a DCB. However, randomized data are currently limited. In a small retrospective study including 42 consecutive patients with diffuse de novo or in-stent restenosis treated with a polymeric-based BRS (ABSORB, Abbott Vascular, USA) implantation (larger proximal segment) and DCB inflation (smaller distal segment or bifurcation side branch), procedural success was obtained in all patients, but three (7.3%) patients required bail-out scaffolding for DCB-related dissections. At a median follow-up of 12 months, there were no cases of cardiac death, target vessel myocardial infarction, or BRS/DCB segment thrombosis. Ischemia-driven target lesion revascularization occurred in two (4.7%) BRS-treated segments. These findings suggest that a hybrid strategy using BRS and DCB in different segments in patients with long diffuse CAD is feasible and associated with encouraging clinical outcomes.

With increasingly higher rates of diffuse coronary lesions to be treated by means of PCI, and still suboptimal long-term results using the current DES, the need for a new approach to treat these lesions represents an unmet clinical need. Freesolve (Biotronik AG, Bülach, Switzerland) bioresorbable scaffold, with a 12-month resorption time, allows for a long-term metal-free vessel, while at the same time providing the temporary scaffolding benefits. Recent studies demonstrate compelling safety data, low TLF rates even in the long-term, and low rates of scaffold thrombosis even in more complex patients. 5. Coronary physiology assessment following percutaneous coronary intervention Intracoronary physiological assessment is acknowledged as a valuable strategy to identify the presence of flow-limiting epicardial stenoses in patients planned for PCI. Numerous large-scale, prospective, multicenter, randomized outcome trials have demonstrated improved clinical outcomes when measuring fractional flow reserve (FFR) with a coronary pressure wire to guide decision-making regarding coronary revascularization in the cardiac catheterization laboratory. However, PCI does not guarantee optimal myocardial revascularization, i.e., restoration of normal epicardial conductance, and recent studies have shown that residual pressure gradients remain in 10-36% of cases despite angiographically successful PCI. During the last years, coronary physiology assessment following PCI has emerged as a valuable tool to assess and potentially optimize the results of percutaneous coronary revascularization. Post-PCI intracoronary pressure measurements can identify residual flow-limiting disease, differentiate residual focal lesions from diffuse disease and provide prognostic information. In patient-level meta-analysis of 28 studies from 17 cohorts including a total of 5,277 patients with 5,869 vessels who underwent FFR measurement after DES implantation lower post-PCI FFR significantly increased the risk of target vessel failure (TVF) (adjusted hazard ratio \[HR\] per 0.01 FFR decrease, 1.04; 95% CI, 1.02-1.05; p\<0.001). The risk of cardiac death or myocardial infarction also increased inversely with po

• Vessel-level FFRangio value after index PCI [Срок оценки: After index PCI]
• Vessel-level FFRangio value at 12-month follow-up [Срок оценки: 12 months]
• Rate of target vessel failure [Срок оценки: 12 months]