ILUMIEN IV: OPTIMAL Percutaneous Coronary Intervention (PCI)

Inclusion Criteria (all must be present)

• Subject must be at least 18 years of age.
• Subject must have evidence of myocardial ischemia (e.g., stable angina, silent ischemia (ischemia in the absence of chest pain or other anginal equivalents), unstable angina, or acute myocardial infarction) suitable for elective PCI.
• Patients undergoing planned XIENCE stent implantation during a clinically indicated PCI procedure meeting one or more of the following criteria:

A) High clinical-risk, defined as;

i. Medication-treated diabetes mellitus, AND/OR

B) High angiographic-risk lesion(s), with at least one target lesion in each target vessel planned for randomization meeting at least one of the following criteria;

i. Target lesion is the culprit lesion responsible for either:

• NSTEMI, defined as a clinical syndrome consistent with an acute coronary syndrome and a minimum troponin of 1 ng/dL (may or may not have returned to normal), OR
• STEMI >24 hours from the onset of ischemic symptoms

ii. long or multiple lesions (defined as intended total stent length in any single target vessel ≥28 mm),

Note: For a long target lesion, this would permit treatment by a single long stent or overlapping stents.

Note: For up to two target lesions located in a single target vessel and treated with non-overlapping stents, they may be located in a continuous vessel or split up between a main vessel and a side branch.

iii. bifurcation intended to be treated with 2 planned stents (i.e. in both the main branch and side branch), and where the planned side branch stent is ≥ 2.5 mm in diameter by angiographic visual estimation.

iv. angiographic severe calcification (defined as angiographically visible calcification on both sides of the vessel wall in the absence of cardiac motion),

v. chronic total occlusion (CTO) (enrolment and randomization in this case performed only after successful antegrade wire escalation crossing and pre-dilatation)

vi. in-stent restenosis of diffuse or multi-focal pattern. Lesion must be at or within the existing stent margin(s) and have angiographically visually-assessed DS ≥70% or DS ≥50% with non-invasive or invasive evidence of ischemia

• All target lesions (those lesions to be randomized) must have a visually estimated or quantitatively assessed %DS of either ≥70%, or ≥50% plus one or more of the following: an abnormal functional test (e.g. fractional flow reserve, stress test) signifying ischemia in the distribution of the target lesion(s) or biomarker positive ACS with plaque disruption or thrombus.

Note: For purposes of study eligibility, a minimum troponin of 1 ng/dL at the time of screening will be considered biomarker positive.

• All target lesions must be planned for treatment with only ≥2.5 mm and ≤3.5 mm stents and post-dilatation balloons based on pre-PCI angiographic visual estimation.
• No more than 2 target lesions requiring PCI are present in any single vessel., and no more than 2 target vessels are allowed. Thus, up to 4 randomized target lesions per patient in a maximum of 2 target vessels are allowed, including branches. The intended target lesions will be declared just prior to randomization.

Note: A lesion is defined as any segment(s) of the coronary tree, no matter how long, which is planned to be covered with one contiguous length of stent, whether single or overlapped. A bifurcation counts as a single lesion even if the side branch is planned to be treated.

Note: All lesions in a randomized target vessel that are intended to be treated by PCI are designated as target lesions, and at least one target lesion in each randomized target vessel must meet angiographic high-risk inclusion criteria summarized above in 3B). The only exception is for patients who qualify for the trial on the basis of medication-treated diabetes, in which case no target lesion is required to meet angiographic high-risk inclusion criteria.

• All target lesions intended to be treated by PCI in the target vessel are