XIENCE 90: A Safety Evaluation of 3-month DAPT After XIENCE Implantation for HBR Patients.

A. Primary Objective:

To show non-inferiority of the primary endpoint of all death or all MI (modified ARC) from 3
to 12 months following XIENCE implantation in HBR subjects with HBR treated with 3-month DAPT
compared to a historical control after propensity score adjustment.

B. Secondary Objective:

- To show superiority of the major secondary endpoint of major bleeding (Bleeding Academic
Research Consortium [BARC] type 2-5) from 3 to 12 months following XIENCE implantation
in HBR subjects treated with 3-month DAPT compared to a historical control after
propensity score adjustment.

- To evaluate stent thrombosis (ARC definite/probable) from 3 to 12 months following
XIENCE implantation in HBR subjects treated with 3-month DAPT against a performance goal
(PG).

Approximately 2,000 subjects from approximately 100 sites globally will be enrolled, with at
least 50% of subjects in the United States (US) and subject registration was capped at 300
per site.

All registered subjects will be followed at 3, 6 and 12 months post index procedure.

The data collected from this study will be compared with the historical control of
non-complex HBR subjects treated with standard DAPT duration of up to 12 months from the
XIENCE V USA study, which is a US post-approval study to evaluate the safety of XIENCE V
EECSS in "all-comer" population under real-world setting.

Inclusion Criteria:

1. Subject is considered at high risk for bleeding (HBR), defined as meeting one or more
of the following criteria at the time of registration and in the opinion of the
referring physician, the risk of major bleeding with > 3-month DAPT outweighs the
benefit:

1. ≥ 75 years of age.

2. Clinical indication for chronic (at least 6 months) or lifelong anticoagulation
therapy.

3. History of major bleeding which required medical attention within 12 months of
the index procedure.

4. History of stroke (ischemic or hemorrhagic).

5. Renal insufficiency (creatinine ≥ 2.0 mg/dl) or failure (dialysis dependent).

6. Systemic conditions associated with an increased bleeding risk (e.g.
hematological disorders, including a history of or current thrombocytopenia
defined as a platelet count <100,000/mm3, or any known coagulation disorder
associated with increased bleeding risk).

7. Anemia with hemoglobin < 11g/dl.

2. Subject must be at least 18 years of age.

3. Subject or a legally authorized representative must provide written informed consent
as approved by the Institutional Review Board (IRB)/Ethics Committee (EC) of the
respective clinical site prior to any study related procedure.

4. Subject is willing to comply with all protocol requirements, including agreement to
stop taking P2Y12 inhibitor at 3 months, if eligible per protocol.

5. Subject must agree not to participate in any other clinical trial for a period of one
year following the index procedure.

Angiographic Inclusion Criteria

1. Up to three target lesions with a maximum of two target lesions per epicardial vessel.
Note:

- The definition of epicardial vessels means left anterior descending coronary
artery (LAD), left circumflex coronary artery (LCX) and right coronary artery
(RCA) and their branches. For example, the patient must not have >2 lesions
requiring treatment within both the LAD and a diagonal branch in total.

- If there are two target lesions within the same epicardial vessel, the two target
lesions must be at least 15 mm apart per visual estimation; otherwise this is
considered as a single target lesion.

2. Target lesion ≤ 32 mm in length by visual estimation.

3. Target lesion must be located in a native coronary artery with visually estimated
reference vessel diameter between 2.25 mm and 4.25 mm.

4. Exclusive use of XIENCE family of stent systems during the index procedure.

5. Target lesion has been treated successfully, which is defined as achievement of a
final in-stent residual diameter stenosis of <20% with final TIMI-3 flow assessed by
online quantitative angiography or visual estimation, with no residual dissection
NHLBI grade ≥ type B, and no transient or sustained angiographic complications (e.g.,
distal embolization, side branch closure), no chest pain lasting > 5 minutes, and no
ST segment elevation > 0.5 mm or depression lasting > 5 minutes.

General Exclusion Criteria

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

2. Subject has a known hypersensitivity or contraindication to aspirin,
heparin/bivalirudin, P2Y12 inhibitors (clopidogrel/prasugrel/ticagrelor), everolimus,
cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers or contrast
sensitivity that cannot be adequately pre-medicated.

3. Subject with implantation of another drug-eluting stent (other than XIENCE) within 9
months prior to index procedure.

4. Subject has a known left ventricular ejection fraction (LVEF) <30%.

5. Subject judged by physician as inappropriate for discontinuation from P2Y12 inhibitor
use at 3 months, due to another condition requiring chronic P2Y12 inhibitor use.

6. Subject with planned surgery or procedure necessitating discontinuation of P2Y12
inhibitor within 3 months following index procedure.

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

8. Subject intends to participate in an investigational drug or device trial within 12
months following the index procedure.

9. Pregnant or nursing subjects and those who plan pregnancy in the period up to 1 year
following index procedure. Female subjects of child-bearing potential must have a
negative pregnancy test done within 7 days prior to the index procedure per site
standard test.

Note: Female patients of childbearing potential should be instructed to use safe
contraception (e.g., intrauterine devices, hormonal contraceptives: contraceptive
pills, implants, transdermal patches, hormonal vaginal devices, injections with
prolonged release.) It is accepted, in certain cases, to include subjects having a
sterilised regular partner or subjects using a double barrier contraceptive method.
However, this should be explicitly justified in special circumstances arising from the
study design, product characteristics and/or study population

10. Subject is part of a vulnerable population, defined as subject whose willingness to
volunteer in a clinical investigation could be unduly influenced by the expectation,
whether justified or not, of benefits associated with participation or of retaliatory
response from senior members of a hierarchy in case of refusal to participate.
Examples of populations which may contain vulnerable subjects include: individuals
with lack of or loss of autonomy due to immaturity or through mental disability,
persons in nursing homes, children, impoverished persons, subjects in emergency
situations, ethnic minority groups, homeless persons, nomads, refugees, and those
incapable of giving informed consent. Other vulnerable subjects include, for example,
members of a group with a hierarchical structure such as university students,
subordinate hospital and laboratory personnel, employees of the sponsor, members of
the armed forces, and persons kept in detention.

11. Subject is currently participating in another clinical trial that has not yet
completed its primary endpoint.

Angiographic Exclusion Criteria

1. Target lesion is in a left main location.

2. Target lesion is located within an arterial or saphenous vein graft.

3. Target lesion is restenotic from a previous stent implantation.

4. Target lesion is a total occluded lesion (TIMI flow 0).

5. Target lesion contains thrombus as indicated in the angiographic images (per SYNTAX
score thrombus definition).

6. Target lesion is implanted with overlapping stents, whether planned or for bailout.

Note: If there is more than one target lesion, all target lesions must satisfy the
angiographic eligibility criteria. Non-target lesion (i.e., lesions that do not meet the
angiographic criteria listed above) treatments are not allowed during the index procedure.