SYNergy Stent® System Implantation With Mandatory Intra-VascularUltra-Sound Guidance and Dual Anti-Platelet Therapy

SYNergy Stent® System Implantation With Mandatory Intra-VascularUltra-Sound Guidance to Examine the Safety of Cessation of Dual Anti-Platelet Therapy in High Bleeding Risk Patients at One Month

The purpose of this study is to see if one month of dual antiplatelet therapy (DAPT) combined with the placement of the Synergy® Stent with IVUS (intravascular ultrasound) is safe for patients who are at high risk of bleeding (HBR).

DAPT or Dual Antiplatelet Therapy is a combination of two medications given after a percutaneous coronary intervention (PCI) with a drug eluting stent. DAPT is used to help make the platelets in your blood slick so they don't clump or stick together. If the platelets stick together and form a blood clot in the stent it is called a stent thrombosis and will cause an immediate heart attack or MI.

The medications used for DAPT are low dose Aspirin (81mg) and one of three (3) antiplatelet medications: ticagrelor (Brilinta), clopidogrel (Plavix) or prasugrel (Effient) . The standard length of time to take DAPT after a stent placement is 6 months to 1 year. Dapt is associated with an increased risk of bleeding. Because you are considered to be at a high risk for bleeding due to one or a combination of reasons this study is trying to determine if a shorter use of DAPT in combination with the Synergy® stent and an imaging tool called IVUS used during your PCI procedure is safe and effective to reduce the potential for serious bleeding events and early stent thrombosis.

The Synergy® stent was chosen because of its enhanced method of healing and reduced inflammation of the artery after placement. Because of this the Synergy stent may be a better choice for patients who are at high risk for bleeding and could benefit from a shortened period of DAPT.

Intravascular ultrasound or IVUS provides a visual image of the inside of the coronary artery. It is used in patients undergoing PCI or stent placement for a few reasons; prior to placing the stent it is used to measure the artery's width to select the proper size diameter of a stent, also the length of the blockage to select the appropriate length of the stent and to visualize the amount of narrowing or blockage. After the stent is placed IVUS is used to make sure the stent itself is fully expanded and sits up against the wall of the artery. This is called apposition. If stents are not fully expanded and sit up against the wall of the artery early reblockage may occur. In short the IVUS aids in the ideal placement of the stent.

By using the combination of the Synergy® Stent with the IVUS the expectation is to safely decrease the length of time you take DAPT from 6-12 months to 1 month. With the benefit of decreasing the risk of bleeding events.

Inclusion Criteria:

• Subject is considered at high risk for bleeding, defined as meeting one or more of the following criteria at the time of enrollment:
• Greater than or equal to 75 years of age and, in the opinion of the investigator, the risk of bleeding associated with >1 months of DAPT outweighs the benefit,
• need for chronic or lifelong anticoagulation therapy
• history of major bleeding (severe/life threatening or moderate bleeding based on the GUSTO classification) within 12 months of the index procedure,
• history of stroke (ischemic or hemorrhagic),
• renal insufficiency (creatinine ≥2.0 mg/dl) or failure (dialysis dependent),
• platelet count ≥20,000/μLto ≤100,000/μL (microliters)
• In the opinion of investigator, patient is at significant risk of falling
• Patient abuses drugs or alcohol
• Hemoglobin ≤11.0 u/dl 2. Subject must be 18 years of age 3. Subject must be able to take study required dual antiplatelet therapy (1 month of P2Y12 inhibitor and aspirin, 13 months of antiplatelet monotherapy) 4. Subject is willing to comply with all protocol requirements, including agreement to stop taking P2Y12 inhibitor at the 1-month milestone if eligible per protocol 5. Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific procedures are performed

Angiographic Inclusion Criteria:

1. Subject must have had implantation of at least one Synergy Stent and the use of Boston Scientific IVUS for guided stent implantation

2. All implanted stents must be post dilated and must meet the following IVUS success criteria:

   • treated lesions in which the stent cross sectional area exceeds the distal reference cross sectional area
   • if the stent cross sectional area is less than the distal reference cross sectional area additional post-dilatation must be performed, followed by IVUS
   • above IVUS criteria must be met after the 2nd post dilatation NOTE: if the IVUS criteria is not met after the 2 post dilatation the patient is excluded

3. Stent procedure performed by an approved investigator

4. Vessel diameter ≥ 2.25 mm and ≤4.0 mm and lesion length ≤34mm

5. Pre-dilatation is up to the discretion of the investigator

Exclusion Criteria:

1. Subject with an indication for the index procedure of acute ST elevation MI (STEMI)

2. Subject with an indication for the index procedure of Non ST elevation MI (NSTEMI), based on the 3rd Universal MI definition

3. Subject with treatment with another coronary stent, other than SYNERGY Stent during the index procedure

4. Subject with a planned staged procedure >7 days following the index procedure. (Note: Planned staged procedures are allowed if performed within 7 days of the index procedure and only when SYNERGY stents are used for both the index and staged procedure). Discontinuation of DAPT should occur 1 month after the last PCI procedure is completed.

5. A staged procedure cannot in a 3rd epicardial vessel if 2 epicardial vessels were treated during the index procedure

6. Subject has a known allergy to: contrast (that cannot be adequately pre-medicated), the SYNERGY Stent system or protocol-required concomitant medications (e.g., everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors and aspirin)

7. Subject previously treated at any time with intravascular brachytherapy

8. Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding

9. Subject is participating in an investigational drug or device clinical trial that has not reached its primary endpoint (Note: registry, observational, data collection studies are not exclusionary)

10. Subject intends to participate in an investigational drug or device clinical trial within 12 months following the index procedure (Note: registry, observational, data collection studies are not exclusionary)

11. Subject is judged inappropriate for discontinuation from P2Y12 inhibitor use at 1 month, due to another condition requiring chronic P2Y12 inhibitor use

    • if at the 30 day visit, the patient has had a peri-procedural NSTEMI with an enzyme elevation >5% of the upper 99th percentile of either creatine kinase-myocardial band (CK-MB) or Troponin, the patient should not be taken off DAPT

12. Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor within 1 month following index procedure

13. Subject is a woman who is pregnant or nursing

14. Subject with a current medical condition with a life expectancy of less than 12 months

15. Subject with implantation of a drug-eluting stent other than SYNERGY Stent within 11 months prior to index procedure

16. Have been previously consented for this trial and screen failed

17. Any other clinically significant comorbidities, which in the judgement of the investigator, could compromise compliance with the protocol, interfere with interpretation of the study results, or predispose the patient to safety risks.

Angiographic Exclusion Criteria:

1. Target lesion(s) is located within a saphenous vein graft or an arterial graft

2. TIMI (Thrombolysis In Myocardial Infarction) flow 0 (total occlusion)

3. Target lesion(s) is located in the left main

4. Potential Target lesion(s) that involve a complex bifurcation (i.e. bifurcation lesion requiring treatment with more than one stent)

5. Thrombus, or possible thrombus, present in the target vessel (by visual estimate)

6. Patients requiring a treatment of more than two native epicardial vessels

7. More than three lesions in two epicardial vessels unless they can be covered in one stent

8. In-stent restenosis of target lesion

9. Treatment of non-target lesions or lesions not treated with a Synergy stent

10. Subject who did not receive Boston Scientific IVUS guided stent implantation and assessment

11. Any target lesion that has not been post dilated and has not had post dilatation IVUS

12. Patients who do not meet the following IVUS success criteria:

    • target lesion(s) in which the stent cross sectional area is less than the distal reference cross sectional area and additional post-dilatation should be performed, followed by repeat IVUS.

NOTE: if the IVUS criteria is not met after the 2nd post dilatation, the patient is excluded