• Primary Endpoint: In-segment late loss (LL) at 240 days
• Major Secondary Endpoint: Ischemia driven target vessel failure (TVF) at 270 days

• Major Secondary Endpoint: Ischemia Driven Target Vessel Failure (ID-TVF) [ Time Frame: 270 days ] [ Designated as safety issue: Yes ]
• Target Vessel Failure (TVF) [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
• Target Vessel Failure (TVF) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
• Target Vessel Failure (TVF) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Target Vessel Failure (TVF) [ Time Frame: 2 year ] [ Designated as safety issue: No ]
• Ischemia Driven Target Lesion Revascularization (ID-TLR) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
• Ischemia Driven Target Lesion Revascularization (ID-TLR) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
• Ischemia Driven Target Lesion Revascularization (ID-TLR) [ Time Frame: 270 days ] [ Designated as safety issue: No ]
• Ischemia Driven Target Lesion Revascularization (ID-TLR) [ Time Frame: 1 years ] [ Designated as safety issue: No ]
• Ischemia Driven Target Lesion Revascularization (ID-TLR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Ischemia Driven Target Vessel Revascularization (ID-TVR) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
• Ischemia Driven Target Vessel Revascularization (ID-TVR) [ Time Frame: 180 days ] [ Designated as safety issue: No ]
• Ischemia Driven Target Vessel Revascularization (ID-TVR) [ Time Frame: 270 days ] [ Designated as safety issue: Yes ]
• Ischemia Driven Target Vessel Revascularization (ID-TVR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Ischemia Drive Target Vessel Revascularization (ID-TVR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Ischemia Driven Major Adverse Cardiac Event (MACE) [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
• Ischemia Driven Major Adverse Cardiac Event (MACE) [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
• Ischemia Driven Major Adverse Cardiac Event (MACE) [ Time Frame: 270 days ] [ Designated as safety issue: Yes ]
• Ischemia Driven Major Adverse Cardiac Event (MACE) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
• Ischemia Driven Major Adverse Cardiac Event(MACE) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• In-stent % Angiographic Binary Restenosis (% ABR) Rate [ Time Frame: at 240 days ] [ Designated as safety issue: No ]
• In-segment % Angiographic Binary Restenosis (% ABR) Rate [ Time Frame: 240 days ] [ Designated as safety issue: No ]
• Persisting Incomplete Stent Apposition, Late-acquired Incomplete Stent Apposition, Aneurysm, Thrombosis, and Persisting Dissection [ Time Frame: at 240 days ] [ Designated as safety issue: No ]
• Acute Success: Clinical Device [ Time Frame: In-hospital ] [ Designated as safety issue: Yes ]
• Acute Success: Clinical Procedure [ Time Frame: In-hospital ] [ Designated as safety issue: No ]
• Proximal Late Loss [ Time Frame: at 240 days ] [ Designated as safety issue: No ]
• Distal Late Loss [ Time Frame: 240 days ] [ Designated as safety issue: No ]
• In-stent Late Loss [ Time Frame: at 240 days ] [ Designated as safety issue: No ]
• % Volume Obstruction (% VO) [ Time Frame: at 240 days ] [ Designated as safety issue: No ]
• In-stent % Diameter Stenosis (% DS) [ Time Frame: at 240 days ] [ Designated as safety issue: No ]
• In-segment % Diameter Stenosis (% DS) [ Time Frame: 240 days ] [ Designated as safety issue: No ]

• · TVF at 30, 180 days, and 1, 2, 3, 4, and 5 years
• · Ischemia driven target lesion revascularization (TLR) at 30, 180 and 270 days, and 1, 2, 3, 4, and 5 years
• · Ischemia driven major adverse cardiac event (MACE) at 30, 180 and 270 days and 1, 2, 3, 4, and 5 years
• · Proximal and distal LL at 240 days
• · In-stent LL at 240 days
• · In-stent and in-segment % angiographic binary restenosis (% ABR) rate at 240 days
• · In-stent % volume obstruction (% VO) at 240 days

This study is divided into 5 arms:

1. Randomized Clinical Trial (RCT): Prospective, randomized, active-controlled, single blind, parallel two-arm multi-center clinical trial in the United States (US) comparing XIENCE V® Everolimus Eluting Coronary Stent System (CSS) (2.5, 3.0, 3.5 mm diameter stents) to the Food and Drug Administration (FDA) approved commercially available active control TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System
2. US 2.25 mm non-randomized arm using 2.25 mm diameter XIENCE V® Everolimus Eluting CSS
3. US 4.0 mm non-randomized arm using 4.0 mm diameter XIENCE V® Everolimus Eluting CSS
4. US 38 mm non-randomized arm using 38 mm in length XIENCE V® Everolimus Eluting CSS
5. Japanese non-randomized arm using XIENCE V® Everolimus Eluting CSS (2.5, 3.0, 3.5, 4.0 mm diameter stents) in Japan

The TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent System is Manufactured by Boston Scientific.

The purpose of the SPIRIT III clinical trial is to evaluate the safety and efficacy of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS). The XIENCE V® EECS (XIENCE V® arm) will be compared to an active control group represented by the FDA approved commercially available Boston Scientific TAXUS® EXPRESS2™ Paclitaxel-Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System (TAXUS® arm).

The SPIRIT III clinical trial consists of a randomized clinical trial (RCT) in the US which will enroll approximately 1,002 subjects (2:1 randomization XIENCE V® EECS : TAXUS® EXPRESS2™ PECS) with a maximum of two de novo native coronary artery lesion treatment within vessel sizes >= 2.5 mm and <= 3.75 mm.

The SPIRIT III clinical trial also consists of three concurrent US non-randomized arms (2.25 mm diameter stent, 4.0 mm diameter stent and 38 mm length stent arms) and one Japanese non-randomized arm as follows:

1. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 2.25 mm and < 2.5 mm and lesion length <= 22 mm will be enrolled concurrently in the US 2.25 mm non-randomized treatment arm
2. 80 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 3.75 mm and >= 4.25 mm and lesion length <= 28 mm will be enrolled concurrently in the US 4.0 mm non-randomized treatment arm
3. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 3.0 mm and < 4.25 mm and lesion length > 24 mm and < 32 mm will be enrolled concurrently in the US 38 mm non-randomized treatment arm.
4. 88 Japanese subjects with a maximum of two de novo native coronary artery lesions within vessel sizes >= 2.5 mm and <= 4.25 mm and lesion length <= 28 mm will be enrolled concurrently in the non-randomized Japanese arm.

All subjects in the RCT and the four non-randomized arms will be screened per the protocol required inclusion/exclusion criteria. The data collected will be compared to data from the subjects enrolled into the TAXUS® arm of US RCT.

Subjects enrolled in the US RCT will be sub-grouped based on whether they will have an angiographic and/or an intravascular ultrasound (IVUS) follow-up at 240 days as follows:

Group A: Angiographic and IVUS follow-up at 240 days (N=240) Group B: Angiographic follow-up at 240 days (N=324) Group C: No angiographic or IVUS follow-up (N=438)

All subjects will have clinical follow-up at 30, 180, 240 and 270 days (Data collected through 270 days will be submitted as the primary data set for US and Japanese market approval), and 1, 2, 3, 4, and 5 years (for annual reports).

All subjects enrolled into three US non-randomized arms (N=105 for 2.25 mm arm, N=80 for 4.0 mm arm and N=105 for 38 mm stent arm) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic follow-up at 240 days. No IVUS follow-up is required for subjects enrolled in these arms.

All subjects enrolled into the Japanese non-randomized arm (N=88) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic and IVUS follow-up at 240 days.

All subjects who receive a bailout stent will be assigned to Group A follow-up subgroup (angiographic and IVUS follow-up at 240 days after the index procedure), regardless of their primary assignment at randomization. At sites without IVUS capability, subjects receiving bailout stent will be assigned to Group B follow-up subgroup (angiographic follow-up at 240 days after the index procedure). Angiographic follow-up is required for all bailout subjects at 240 days.

Data from the US RCT will be submitted to the FDA as the primary data set for product approval for RVD >= 2.5 mm and <= 3.75 mm (2.5 mm, 3.0 mm and 3.5 mm stents). Combined data of the US trial/Japanese non-randomized arm will be submitted to the Japanese Ministry of Health, Labor and Welfare (MHLW) for Japanese approval for RVD>=2.5 mm and <= 4.25 mm (2.5 mm, 3.0 mm 3.5 mm and 4.0 mm stents). Data from the Japanese non-randomized arm will be submitted to the FDA as additional safety data. Data from the US non-randomized arms of the trial will be the primary data sets for approval for 2.25 mm diameter stent (RVD > 2.25 mm and < 2.5 mm), 4.0 mm diameter stent (RVD > 3.75 mm and <= 4.25 mm) and 38 mm length stent (RVD > 3.0 mm and <= 4.25 mm and lesion length > 24 mm and <= 32 mm), respectively in the US.

A pharmacokinetic substudy will be carried out in a minimum of 5 pre-determined sites in the US and a minimum of 5 pre-determined sites in Japan. In the US, the pharmacokinetics (PK) of everolimus, as delivered by the XIENCE V® EECS will be analyzed in a subset of 15 subjects (minimum) with single vessel/lesion treatment, and up to 20 subjects with dual vessel/lesion treatment, respectively. In Japan, a minimum of 10 subjects with single vessel/lesion treatment and up to 20 subjects with dual vessel/lesion treatment will have a PK measurements performed. These subsets will include subjects receiving overlapping stents.

• Stents
• Coronary Artery Disease
• Total Coronary Occlusion
• Coronary Artery Restenosis
• Stent Thrombosis
• Vascular Disease
• Myocardial Ischemia
• Coronary Artery Stenosis

• Device: XIENCE V® Everolimus Eluting Coronary Stent
• Device: TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent

• Experimental: XIENCE V® Everolimus Eluting Coronary Stent System
• Active Comparator: TAXUS® EXPRESS2™Paclitaxel Eluting Coronary Stent System

• Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Mahaffey KW, Cutlip DE, Fitzgerald PJ, Sood P, Su X, Lansky AJ; SPIRIT III Investigators. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. JAMA. 2008 Apr 23;299(16):1903-13.
• Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Caputo R, Xenopoulos N, Applegate R, Gordon P, White RM, Sudhir K, Cutlip DE, Petersen JL; SPIRIT III Investigators. Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial. Circulation. 2009 Feb 10;119(5):680-6. Epub 2009 Jan 26.
• Lansky AJ, Ng VG, Mutlu H, Cristea E, Guiran JB, Midei M, Newman W, Sanz M, Sood P, Doostzadeh J, Su X, White R, Cao S, Sudhir K, Stone GW. Gender-based evaluation of the XIENCE V everolimus-eluting coronary stent system:: clinical and angiographic results from the spirit III randomized trial. Catheter Cardiovasc Interv. 2009 Mar 24; [Epub ahead of print]

Inclusion Criteria:

• Target lesion(s) must be located in a native epicardial vessel with visually estimated diameter between >= 2.25 mm and <= 4.25 mm and a lesion length <= 32 mm
• The target lesion(s) must be in a major artery or branch with a visually estimated stenosis of >= 50% and < 100% with a thrombolysis in myocardial infarction (TIMI) flow of >= 1
• Non-study, percutaneous intervention for lesions in a non-target vessel is allowed if done >= 90 days prior to the index procedure (subjects who received brachytherapy will be excluded from the trial)

Exclusion Criteria:

• Located within an arterial or saphenous vein graft or distal to a diseased (vessel irregularity per angiogram and > 20% stenosed lesion by visual estimation) arterial or saphenous vein graft
• Lesion involving a bifurcation >= 2 mm in diameter or ostial lesion > 50% stenosed by visual estimation or side branch requiring predilatation
• Located in a major epicardial vessel that has been previously treated with brachytherapy
• Located in a major epicardial vessel that has been previously treated with percutaneous intervention < 9 months prior to index procedure
• Total occlusion (TIMI flow 0), prior to wire passing
• The target vessel contains thrombus
• Another significant lesion (> 40% diameter stenosis [DS]) is located in the same epicardial vessel as the target lesion