The study seeks to address the clinical question of how effectively a novel cutting balloon (Wolverine™) can modify calcified lesions for stent implantation in comparison with a non-compliant (NC) balloon, particularly when used alongside a bioabsorbable polymer-coated everolimus-eluting coronary stent (Synergy™).

Most previous researches on cutting balloons focused on only severe calcifications and had limitations such as small sample sizes with retrospective designs, emphasizing on short-term imaging outcomes. This study differs by including mild to severe calcifications and evaluating long-term clinical outcomes, intraprocedural factors, and operator convenience. It aims to provide evidence that could potentially expand the indications for cutting balloon use and inform insurance coverage policies.

The objective of the study is to test the safety and efficacy of the cutting balloon in preparing calcified coronary lesions for stent insertion compared to conventional methods.

1. Background

1. Which clinical question shall be answered? Heavily calcified lesions respond poorly to conventional balloon angioplasty when stents are implanted in incompletely modified lesions, resulting in incomplete and asymmetrical stent expansion. Inadequate calcium and plaque modification is related to worse clinical outcomes. In addition, incomplete modification and preparation of calcified lesions adversely affect the number of balloons, amount of contrast, procedure time, and stent delivery failure. Periprocedural factors, such as the amount of contrast medium and procedure time, are also known to be related to adverse clinical outcomes and in-hospital complication rates. Various devices, such as cutting balloons, spiral balloons, and rotational atherectomy devices, have been used to modify calcium lesions. The cutting balloon has four blades surrounding the balloon. When the balloon is inflated, the blades initiate a score into the plaque, after which the shear force applied by the balloon inflation propagates the crack and results in lumen enlargement. However, evidence related to use of the cutting balloon for various degrees of calcified lesions is limited. In addition, despite the advantages of the cutting balloon in the treatment of calcium lesions, investigations designed to focus on intraprocedural and operator-oriented endpoints, such as the number of balloons used, procedure time, and the total amount of contrast medium used, are also rare. Moreover, bioabsorbable polymer-coated coronary stents have proven to be safe and effective for the treatment of coronary artery diseases, including calcified lesions. Therefore, in this study, the investigators aim to evaluate the safety and efficacy including intraprocedural and operator-oriented outcomes of a novel cutting balloon (Wolverine™, Boston Scientific, Natick, Massachusetts(MA), USA) compared with a non-compliant (NC) balloon in the treatment of patients with various degrees of calcified lesions, including mild to heavily calcified lesions, who are treated with intravascular ultrasound (IVUS) guided bioabsorbable polymer-coated everolimus-eluting coronary stent (Synergy™, Boston Scientific Corporation, Marlborough, MA, USA) implantation.

2. To what degree has this question already been investigated elsewhere? What are the differentiators to already published studies? The Wolverine balloon (Boston Scientific Corporation) is a novel cutting balloon mounted on a semi-compliant balloon with three or four arthrotomies bonded longitudinally to its surface. Some studies on the use of cutting balloons in the treatment of coronary arteries have been previously reported, but most of them investigated moderately or severely calcified lesions compared with NC balloons. Another limitation of previous studies is that they included a small number of patients and had a retrospective design. In addition, previous studies have mainly focused on periprocedural outcomes based on imaging studies, such as acute luminal gain and cross-sectional area(CSA) using IVUS.

   In this study, the indication of a cutting balloon is not limited to severe calcified coronary artery disease but expanded to mild calcified coronary artery disease, including in-stent restenosis(ISR), to achieve optimal preconditioning for stent implantation through active calcium modification. Apart from the acute phase per-procedural gain of calcium modification, the investigators aim to investigate the long-term endpoints such as major adverse cardiac events(MACE) with aggressive calcium modification and an appropriate type of drug-eluting stent implantation. This trial is to be conducted using a bioabsorbable polymer-coated drug-eluting coronary stent. The SYNERGY stent (Boston Scientific Corporation, Marlborough, MA, USA) is a thin strut (74 μm) of platinum-chromium metal alloy that elutes everolimus from an ultrathin (4 μm) bioabsorbable polymer applied only to the abluminal surface of the stent and resolves within 4 months. After the absorption period of the polymer, only ultrathin (<70 or 80 μm) stent struts remain, and ultrathin stent struts improve clinical outcomes in the treatment of various coronary artery diseases.

   Previously, a few studies have reported the stent crossability of novel cutting balloons for treating calcium lesions. However, studies focusing on intraprocedural operator-centric factors, such as the procedure time, amount of contrast medium, and number of balloons used, are lacking. As previously reported, periprocedural and intraprocedural factors, such as the amount of contrast medium and procedure time, are also related to adverse clinical outcomes in the complex percutaneous coronary intervention(PCI) era. As (Effect of cutting balloon after rotational atherectomy in severely calcified coronary artery lesions as assessed by optical coherence tomography) reported, the low crossability of the old model cutting balloon makes the operator hesitant to choose a cutting balloon as a first-line option in the treatment of the calcified lesion. However, the crossability of the novel cutting balloon (Wolverine™) was improved and proved to have a higher delivery success rate caused by the induction of superior crossability derived from active calcium modification. In addition, owing to the development of balloon platform technologies, there have been reports on the improvement of stent and balloon crossability in the treatment of calcium lesions with novel cutting balloons compared with old cutting or scoring balloons. In our study, the investigators additionally focus on intraprocedural and operator-centric outcomes, and the total procedure time, number of balloons, and amount of contrast medium used are set as the parameters of the secondary endpoints.

   In conclusion, this study evaluates the efficacy and safety of the novel cutting balloon (Wolverine™) compared to the NC balloon in treating patients with calcified coronary lesions undergoing PCI. It aims to provide insights into the optimal type of balloons for modifying calcium lesions. Additionally, the study seeks to broaden the application of the cutting balloon, exploring its use in a range of coronary calcified lesions from mild to severe. This comparative approach extends to assessing clinical benefits, including intraprocedural and periprocedural outcomes, as well as factors like the total number of balloons used, procedure time, and contrast amount for enhanced operator convenience. Furthermore, the study intends to demonstrate the mid- to long-term clinical advantages of using cutting balloons for aggressive modification of calcified lesions, followed by the implantation of bioabsorbable polymer-coated everolimus-eluting coronary stents (Synergy™, Boston Scientific Corporation, Marlborough, MA, USA). Lastly, given the limited insurance coverage for cutting balloons in some countries, this research also aims to substantiate their use in treating mild stenosis and ISR lesions, potentially influencing broader insurance policy inclusion.

3. Can this question only be answered by a clinical investigation? Although the use of a cutting balloon in the treatment of heavy calcified lesions has been previously proven, the investigators believe that clinical studies are needed to demonstrate the effectiveness of treatment of various calcium lesions including restenosis through this study. In addition, since it is a study that requires results through imaging tests and long-term clinical observation, it is necessary to conduct clinical research. As the basis for the safety of cutting balloons has been sufficiently proven in previous clinical studies, it is considered that there are no ethical problems.

4. Why and for whom is it important to perform this study? The investigators evaluate the efficacy and safety of the novel cutting balloon (Wolverine™) in patients with calcified coronary lesions undergoing PCI and will provide rationale for which type of balloons will optimally modify the calcium lesions. In addition, the investigators attempt to expand the indications of the cutting balloon for the treatment of mild to severe coronary calcified lesions by conducting a comparative study of the NC and cutting balloons in the treatment of calcified lesions.

   The investigators aim to investigate the clinical benefits of intraprocedural and periprocedural outcomes and operator convenience, such as the number of total balloons used, procedure time, and amount of contrast. The scope of insurance coverage for cutting balloons remains limited in some countries; therefore, this study aims to provide evidence for extending insurance coverage to the treatment of mild stenosis and ISR lesions.

5. What and how will Boston Scientific technology be used? The following devices will be used: 1) Wolverine (Boston Scientific, Natick, MA, USA) cutting balloon, 2) bioabsorbable polymer-coated everolimus-eluting coronary stent (Synergy™, Boston Scientific Corporation, Marlborough, MA, USA), and 3) NC balloon (the type of NC balloon will be decided at the operator's discretion).

   PCI and stent implantation will be performed according to the current guidelines using standard interventional techniques. The interventional strategy, balloon size, and stent selection will be based on the discretion of the same operator for all patients. Modification of the atheroma using rota-ablation will be performed at the operator's discretion in cases of balloon-uncrossable lesions, and these cases will be excluded from enrollment. After pre-dilation, all patients would be treated with bioabsorbable polymer-coated everolimus-eluting coronary stent (Synergy™, Boston Scientific Corporation, Marlborough, MA, USA). After regular coronary angiography, IVUS will be performed at baseline (before pre-dilatation) and repeated immediately after stent implantation in all cases. IVUS will be performed using an OptiCross™ 60 MHz (Scientific Corporation, Maple Grove, Minnesota(MN), USA). After intracoronary injection of nitroglycerin, the IVUS catheter will be carefully advanced distal to the culprit lesion under fluoroscopic guidance and then withdrawn automatically at 0.5 mm/s to perform the imaging sequence, which begins 20 mm distal to the culprit lesion and ends at the aorto-ostial junction.

6. Is the device approved for this indication used in this study? Cutting balloon has already been approved as a treatment option for treating coronary calcified lesions. All human and animal studies were approved by the appropriate ethics committee and were, therefore, performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. In addition, this study will be approved by the ethics committee of each participating hospital and center.

2. Study Objective Calcified coronary lesions respond inappropriately to conventional balloon angioplasty, resulting in inadequate lesion preparation and incomplete stent expansion. This prospective randomized study aims to evaluate the safety and efficacy of cutting balloon angioplasty for various degrees of calcified coronary lesions treated with a novel bioabsorbable polymer-coated everolimus-eluting coronary stent.

Inclusion Criteria:

1. Coronary artery disease including ISR or de novo lesion with a stenosis of ≥ 70%
2. Target lesion calcification (an arch of calcium at least 100 degrees) was confirmed by imaging studies
3. A reference vessel diameter between 2.0 and 4.0mm and deemed suitable for PCI

Exclusion Criteria:

1. Extremely tortuous or angulated lesions
2. Lesions with dissection before balloon pre-dilatation
3. Lesions within the vein graft
4. Extremely narrow lesions which need to rotational atherectomy
5. STEMI
6. Comorbidities which preclude the achievement of one year follow up

Open label