Multi-centre, randomised clinical trial with anticipated 17 European centres: in the Netherlands, Belgium, Germany and UK. Patients with a dysfunctional bypass graft with a clinical indication for revascularization will be randomized to either PCI of the native vessel or PCI of the dysfunctional venous bypass graft. 584 patients with a a clinical indication for percutaneous coronary intervention and a dysfunctional graft on the target vesselional venous bypass graft are planned to be enrolled during 3 years.Study objectives: to investigate the clinical and angiographic outcome of native vessel PCI compared to PCI of venous bypass graft in patients with a dysfunctional venous bypass graft with a clinical indication for revascularization. 1 year and 5 years, follow-up will be performed by means of a telephonic visit. After 3 years patients will be admitted to undergo a control invasive angiography.The CT-substudy and the PROCTOR registry is planned to be conducted too.

Multi-centre, randomised clinical trial with anticipated 17 European centres: in the Netherlands, Belgium, Germany and UK. Patients with a dysfunctional bypass graft with a clinical indication for revascularization will be randomized to either PCI of the native vessel or PCI of the dysfunctional venous bypass graft. The CT-substudy and the PROCTOR registry is planned to be conducted too (details included in the flow chart).

CCTA substudy Selected patients will be approached for participation in the CCTA substudy of the trial. Participation in this substudy is optional. After written informed consent is obtained patients will undergo a CCTA in an out-patient setting. The CCTA will be performed before the PCI procedure.

PROCTOR registry

Patients can be approached for the registry when :

• PCI have been deemed clinically indicated by the local hartteam, and
• both the lesions in the native vessel and the dysfunctional graft have been deemed technically feasible by the local hartteam,
• the patient does not meet the in- and exclusion criteria for the randomized PROCTOR study or declines to participate in the randomized study.

Patients will be approached for participation and will have one week to consider. Written informed consent is mandatory for participating in the registry. Patients will be followed by telephonic follow-up after 1, 3, and 5 years. No additional study procedures will be performed.

Study objectives:to investigate the clinical and angiographic outcome of native vessel PCI compared to PCI of venous bypass graft in patients with a dysfunctional venous bypass graft with a clinical indication for revascularization.

1. PROCTOR main study

   - Investigate the clinical outcome of native vessel PCI vs. PCI of dysfunctional venous bypass graft with a clinical indication for revascularisation

2. CCTA substudy

   • Investigate prognostic value of CT-derived plaque characteristics for occurrence of MACE following bypass graft PCI
   • Investigate value of CCTA in guidance of CTO PCI procedures

3. PROCTOR Registry - Investigate long-term clinical outcomes in patients with dysfunctional venous bypass graft and an indication for PCI whom are not included in randomised main study.

All patients with a significant stenosis (>50% on coronary angiography) in a venous bypass graft discussed in the local heart team for revascularization will be screened for potential inclusion in the study. Patients will be eligible for inclusion if revascularization is deemed clinically indicated and technically feasible for PCI by the local heart team. The indication for revascularization will be based on symptoms and evidence of ischemia and viability in the target vessel territory. The lesion in the native vessel must be bypassed by a single venous graft or must be connected to a jump graft at the most distal anastomosis of that graft. In jump grafts, the lesion must be located distally to the second-to-last anastomosis. In case both the lesion in the native vessel and the lesion in the graft are deemed technically feasible for PCI, patients will be eligible for inclusion in the randomized study after consideration of in- and exclusion criteria. Patients who do not meet these criteria or decline to participate in the randomized study will be approached for inclusion in the registry. Subsequently patients will be approached for study participation. After being informed, patients will have at least 24 hours to consider participation. An independent physician will be available for extra information, if desired. After obtaining written informed consent, patients will be randomized to either native vessel PCI or PCI of the venous bypass graft. In case of PCI failure, a second attempt can be performed by the operator within one month.

If feasible, it is possible to perform a second attempt in another high-volume center. When successful PCI cannot be accomplished in one or two attempts, cross-over to the other treatment arm may be used as bailout strategy to restore myocardial blood flow to the distal vascular bed of the vessel. Randomization will be performed using an interactive Web-based randomization system, Open Clinica. After 1 and 5 years, follow-up will be performed by means of a telephonic visit. After 3 years patients will be admitted to undergo a control invasive angiography.

Inclusion Criteria:

• A significant stenosis (>50% on angiography) in a venous bypass graft

  • The native lesion must be bypassed by a single graft or must be connected to a jump graft at the most distal anastomosis of that graft
  • In jumpgraft lesions, the lesion must be located distally to the second-to-last anastomosis

• Clinical indication for revascularization as determined by the local heart team (based on symptoms, documented ischemia, and viability).

• Both the native lesion and the venous graft lesion must be deemed suitable for PCI with a commercially available second generation DES.

• Informed consent must be obtained

Exclusion Criteria:

• < 18 years of age
• Target vessel diameter < 2.5 mm
• CABG performed less than 1 year prior to inclusion
• Diameter of the graft > 5.5 mm
• Aneurysm formation in the bypass graft
• Heavy burden of thrombus in the bypass graft (>50% of the bypass graft lumen in ≥2 out of 3 of the proximal, middle or distal third of the bypass graft).
• STEMI at presentation
• NSTEMI patients with ongoing ischemia
• Cardiogenic shock
• Severe kidney disease defined as an eGFR < 30 ml/min.
• Pregnancy
• Estimated life expectancy < 3 year
• Contraindications to PCI