Wall Shear Stress and Neointimal Healing Following PCI in Angulated Coronary Vessels

The past two decades have registered major advances in cardiovascular medicine that have
improved patients' survival and quality of life. One area of major research and innovation is
the field of percutaneous coronary interventions (PCI), a non-surgical procedure used to
treat a narrowed heart artery with stents. Stents are metallic tubular supports placed inside
a blood vessel to relieve an obstruction and restore blood flow to the heart muscle. Stents
could also be coated with a drug (drug-eluting stents - DES) that improves local healing and
inhibits growth of scar tissue (smooth muscle and fibrous cells) within the vessel that
otherwise could lead to re-narrowing.

The investigators study will evaluate two FDA-approved DES, currently in use, with respect to
coronary vessel healing and long term patency. These include the XIENCE Xpedition Everolimus
drug-eluting stent (X-EES) from Abbott Vascular and Resolute Integrity® Zotarolimus
drug-eluting stent (R-ZES) from Medtronic, Inc, both of which have been shown in large
clinical trials to be safe and effective. This study will evaluate the effects of apparently
subtle differences in stent design between these two platforms that may have important
effects on regional plaque response and blood flow dynamics immediately after stent
deployment and stent healing and scar formation at 12 months follow up.

Several aspect of the R-ZES compared to the X-EES design may result in more favorable
regional plaque response and blood flow dynamics immediately after stent deployment. These
include a more compliant stent design made of a single sinusoidal wire with no connector
between struts that is likely to be more comformable to a curved or angulated coronary
vessels. In heart vessels which are not angulated, these features may not make a major
difference in outcomes as studies already suggest. Whereas, in narrowed arteries which are
curved or angulated, the use of X-EES could result in more straightening of the vessel's
natural curvature and more disturbance in flow patterns. In contrast, the use of R-ZES in
angulated arteries could cause less hemodynamic disturbances. There is a great deal of data
suggesting that disturbances in local blood flow patterns and creation of eddy currents
('turbulent' blood flow) could adversely affect stent healing and exacerbate neointimal
tissue growth.

Using two intravascular imaging technologies, the optical coherence tomography (OCT) and
intravascular ultrasound (IVUS), this study aims to investigate differences in scar tissue
coverage within the stented region and the degree of narrowing at the edges of the stent in
patients undergoing clinically-indicated PCI (with R-ZES and X-EES) at 12-month follow-up.

Inclusion Criteria:

1. Patient must be 30 to 80 years old

2. Severe coronary lesion in a vessel with >30 degree angulation requiring PCI

3. Lesion treatable by a single Resolute Integrity or Abbott Xience Xpedition coronary
drug eluting stent (length 15-38 mm).

4. Evidence of myocardial ischemia (e.g., stable or unstable angina, post-infarct angina
or silent ischemia) suitable for PCI.

Subjects with stable angina or silent ischemia and < 70% diameter stenosis must have
objective sign of ischemia as determined by echocardiogram, nuclear scan, ambulatory ECG or
stress ECG. In the absence of noninvasive ischemia, fractional flow reserve (FFR) must be
done and indicative of ischemia.

Exclusion Criteria:

1. Inability to provide informed consent prior to randomization

2. Anatomy requiring coronary artery bypass surgery (CABG)

3. History of prior CABG in the territory of the vessel being considered for PCI

4. Heavily calcified lesion requiring rotablation or other debulking or scoring device
for successful stent deployment

5. Recent (<3 days) ST-elevation myocardial infarction (STEMI)

6. Systolic BP >160mmHg or diastolic BP>100 mmHg or hypotension (BP <90/60 mmHg)

7. Planned surgical procedures in the subsequent 6 months

8. History of hypersensitivity or contraindication to device materials and their
degradants, everolimus, zotarolimus, cobalt, chromium, nickel, platinum, tungsten,
acrylic and fluoro polymers

9. History of any solid organ transplantation or subject is on a waiting list for any
solid organ transplant.

10. Known allergies to clinically utilized anti-thrombotic or anti-platelet agents

11. Unable to tolerate long term dual anti-platelet therapy

12. Pregnancy or lactation

13. Subject has renal insufficiency as defined as an estimated GFR < 30 ml/min/1.73m2.