2.1

Study design and population

This is a single-arm, prospective, open-label registry that enrolled 27 patients from two centers (Laboratory of Invasive Cardiology, Department of Cardiology, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli, Italia, and Laboratory of Invasive Cardiology of Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli, Italia).

Patients were eligible if:

• •
  

  they were aged 18 years and older;

  
  
• •
  

  had a diagnosis of stable or unstable coronary artery disease;

  
  
• •
  

  had ISR lesion in a native coronary;

  
  
• •
  

  reference vessel diameter visually assessed at the target lesion site was ≥ 2.3 mm and ≤ 3.7 mm.

Patients were excluded if:

• •
  

  lesions were located in the left main coronary artery;

  
  
• •
  

  lesions involved a side branch more than 2 mm in diameter;

  
  
• •
  

  there was presence of thrombus in the target vessel.

This study was approved by the ethics committee at both participating institutions and all patients provided written informed consent.

2.2

Study device

The BVS (ABSORB, Abbott Vascular, Santa Clara, CA, USA) consists of a backbone of PLLA coated with poly-D,L-lactide (PDLLA). PLLA eluting everolimus is a semicrystalline polymer. Technical details have been described previously .

2.3

Procedures

Patients were pre-treated with aspirin and a P2Y12 inhibitor. A loading dose of P2Y12 inhibitor was administered before the intervention to P2Y12 inhibitor naïve patients. Full anticoagulation was obtained during the procedure with unfractionated heparin (initial bolus of 70 UI/kg with additional boluses as required to achieve an activated clotting time > 250 s). The use of glycoprotein IIb/IIIa inhibitors was left at operators’ discretion.

ISR lesions were classified according to literature . BVSs were implanted, after mandatory predilation at a pressure not exceeding the rated-burst pressure of 16 atm; the use of scoring balloon was left at the operator’s decision. The BVS should cover 2 mm of non-diseased tissue on either side of the target lesion. Postdilation and OCT imaging was left to the operator’s discretion.

All patients were required to receive more than 75 mg of aspirin daily lifelong and 75 mg of clopidogrel daily for a minimum of 12 months.

2.4

Patient follow-up

All patients underwent a clinical assessment and a structured questionnaire at 30 days and 6, 9 and 12 months. The questionnaire assessed symptoms, groin complications, functional capacity, medication use, hospitalizations, cardiac testing, and emphasized repeat angiography, target vessel revascularization, and mortality. At each time point, in case of symptoms recurrence, patients underwent a myocardial stress test.

In case of symptoms recurrence and non-invasive demonstration of inducible myocardial ischemia, patients underwent to a coronary angiogram.

After 12 months, clinical follow up was systematically continued for a period of 3 months.

2.5

Study end-points

Three physicians have adjudicated any clinical events not involved in patient management.

Procedural success was considered the successful delivery and deployment of the clinical investigation stent at the intended target lesion with attainment of a final residual stenosis of less than 30% of the target lesion by quantitative coronary angiography (QCA).

Clinical success was considered when procedural success was attained without any target vessel-related death, acute myocardial infarction, emergency coronary bypass surgery, stroke, or repeat target vessel revascularization within 7 days of the procedure.

The primary end point was defined as the occurrence of target vessel revascularization (TVR) at 12 months.

Secondary endpoint was the composite of death, myocardial infarction, or need for target vessel revascularization (TVR) according to the Academic Research Consortium (ARC) definitions at 9 months after the index procedure .

2.6

Angiographic analysis

Quantitative coronary angiographic (QCA) analysis was performed offline by an expert analyst using automated edge-detection algorithms. In each lesion, the coronary segment including the stent and 5-mm proximal and distal to the stent edge was analyzed at baseline and at follow-up. The following QCA parameters were measured: reference vessel diameter (RVD), minimal lumen diameter (MLD) and percent diameter stenosis (%DS). Binary restenosis was defined as stenosis > 50% of the luminal diameter in the target lesion .

2.7

OCT imaging and analysis

The OCT imaging was obtained at baseline and only at follow-up and performed after intracoronary nitroglycerin injection, using the C7XR Fourier-Domain System (LightLab Imaging, Westford, Massachusetts). OCT data were analyzed by an expert analyst, who was blinded to clinical presentation and lesion characteristics, using proprietary offline software (LightLab Imaging). Cross-sections at 1-mm intervals (every five frames) within the stent segment and 5 mm proximal and distal to the stent edges were analyzed. Lumen area, stent area, neointimal area and struts apposition were calculated and classified as recommended .

2.8

Statistical analysis

This feasibility study was designed to provide preliminary observations and generate hypotheses for future studies. The sample size was not defined on the basis of an endpoint hypothesis but rather to provide some information about device safety. The sample size requirement was established by assessment of the minimum number of patients needed to provide reliable and non-trivial results.

Results are presented as paired matched angiographic views after procedure and at follow-up. For binary variables, percentages were calculated. Since no formal hypothesis testing was planned for assessment of the success of the study, no statistical adjustment was applied. The p values were considered significant if < 0.05.

2.1

Study design and population

This is a single-arm, prospective, open-label registry that enrolled 27 patients from two centers (Laboratory of Invasive Cardiology, Department of Cardiology, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli, Italia, and Laboratory of Invasive Cardiology of Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli, Italia).

Patients were eligible if:

• •
  

  they were aged 18 years and older;

  
  
• •
  

  had a diagnosis of stable or unstable coronary artery disease;

  
  
• •
  

  had ISR lesion in a native coronary;

  
  
• •
  

  reference vessel diameter visually assessed at the target lesion site was ≥ 2.3 mm and ≤ 3.7 mm.

Patients were excluded if:

• •
  

  lesions were located in the left main coronary artery;

  
  
• •
  

  lesions involved a side branch more than 2 mm in diameter;

  
  
• •
  

  there was presence of thrombus in the target vessel.

This study was approved by the ethics committee at both participating institutions and all patients provided written informed consent.

2.2

Study device

The BVS (ABSORB, Abbott Vascular, Santa Clara, CA, USA) consists of a backbone of PLLA coated with poly-D,L-lactide (PDLLA). PLLA eluting everolimus is a semicrystalline polymer. Technical details have been described previously .

2.3

Procedures

Patients were pre-treated with aspirin and a P2Y12 inhibitor. A loading dose of P2Y12 inhibitor was administered before the intervention to P2Y12 inhibitor naïve patients. Full anticoagulation was obtained during the procedure with unfractionated heparin (initial bolus of 70 UI/kg with additional boluses as required to achieve an activated clotting time > 250 s). The use of glycoprotein IIb/IIIa inhibitors was left at operators’ discretion.

ISR lesions were classified according to literature . BVSs were implanted, after mandatory predilation at a pressure not exceeding the rated-burst pressure of 16 atm; the use of scoring balloon was left at the operator’s decision. The BVS should cover 2 mm of non-diseased tissue on either side of the target lesion. Postdilation and OCT imaging was left to the operator’s discretion.

All patients were required to receive more than 75 mg of aspirin daily lifelong and 75 mg of clopidogrel daily for a minimum of 12 months.

2.4

Patient follow-up

All patients underwent a clinical assessment and a structured questionnaire at 30 days and 6, 9 and 12 months. The questionnaire assessed symptoms, groin complications, functional capacity, medication use, hospitalizations, cardiac testing, and emphasized repeat angiography, target vessel revascularization, and mortality. At each time point, in case of symptoms recurrence, patients underwent a myocardial stress test.

In case of symptoms recurrence and non-invasive demonstration of inducible myocardial ischemia, patients underwent to a coronary angiogram.

After 12 months, clinical follow up was systematically continued for a period of 3 months.

2.5

Study end-points

Three physicians have adjudicated any clinical events not involved in patient management.

Procedural success was considered the successful delivery and deployment of the clinical investigation stent at the intended target lesion with attainment of a final residual stenosis of less than 30% of the target lesion by quantitative coronary angiography (QCA).

Clinical success was considered when procedural success was attained without any target vessel-related death, acute myocardial infarction, emergency coronary bypass surgery, stroke, or repeat target vessel revascularization within 7 days of the procedure.

The primary end point was defined as the occurrence of target vessel revascularization (TVR) at 12 months.

Secondary endpoint was the composite of death, myocardial infarction, or need for target vessel revascularization (TVR) according to the Academic Research Consortium (ARC) definitions at 9 months after the index procedure .

2.6

Angiographic analysis

Quantitative coronary angiographic (QCA) analysis was performed offline by an expert analyst using automated edge-detection algorithms. In each lesion, the coronary segment including the stent and 5-mm proximal and distal to the stent edge was analyzed at baseline and at follow-up. The following QCA parameters were measured: reference vessel diameter (RVD), minimal lumen diameter (MLD) and percent diameter stenosis (%DS). Binary restenosis was defined as stenosis > 50% of the luminal diameter in the target lesion .

2.7

OCT imaging and analysis

The OCT imaging was obtained at baseline and only at follow-up and performed after intracoronary nitroglycerin injection, using the C7XR Fourier-Domain System (LightLab Imaging, Westford, Massachusetts). OCT data were analyzed by an expert analyst, who was blinded to clinical presentation and lesion characteristics, using proprietary offline software (LightLab Imaging). Cross-sections at 1-mm intervals (every five frames) within the stent segment and 5 mm proximal and distal to the stent edges were analyzed. Lumen area, stent area, neointimal area and struts apposition were calculated and classified as recommended .

2.8

Statistical analysis

This feasibility study was designed to provide preliminary observations and generate hypotheses for future studies. The sample size was not defined on the basis of an endpoint hypothesis but rather to provide some information about device safety. The sample size requirement was established by assessment of the minimum number of patients needed to provide reliable and non-trivial results.

Results are presented as paired matched angiographic views after procedure and at follow-up. For binary variables, percentages were calculated. Since no formal hypothesis testing was planned for assessment of the success of the study, no statistical adjustment was applied. The p values were considered significant if < 0.05.