The Real-World Endeavor Resolute versus XIENCE V Drug-Eluting SteNt Study in TwentE

Main study parameter/endpoint:

• Target vessel failure (TVF) at 12 months (according to ARC definitions)



Components of the primary endpoint in hierarchical order:

o Target vessel related death or cardiac death that cannot be clearly attributed to a vessel other than the target vessel. All deaths are considered cardiac, unless an unequivocal noncardiac cause can be established.

o Target vessel related MI (n,%), that is Q-wave or non-Q-wave myocardial infarction that can be related to the target vessel or cannot be related to another vessel.

o Clinically driven repeated target vessel revascularization by means of CABG or PCI (n,%)

• Clinical endpoints at one and three month and 1 and 2 year follow-up (with the exception of TVF at 1 year which is the primary endpoint, as described above):

o Death:

 Cardiac

 Vascular

 Other causes

 All-cause mortality

o Any myocardial infarction:

 Q-wave

 Non Q-wave

o Any revascularisation by means of PCI or Coronary Artery Bypass Grafting (CABG).

o Target vessel related death

o Target vessel related myocardial infarction (MI) (n,%):

 Q-wave myocardial infarction

 Non Q-wave myocardial infarction

o Clinically indicated repeated target vessel revascularization (TVR):

• CABG

• PCI

o Clinically indicated repeated target lesion revascularization (TLR):

• CABG

• PCI

oNew onset of angina pectoris:

 Related to the target vessel.

 Related to another vessel.

 Unspecified.

oStent thrombosis (Definite, Probable, and Possible; ARC definition):

 Early

 Subacute

 Late

 Very late

• Composite endpoint at one and three month and 1 and 2 year follow-up (except TVF at one year follow-up which is already the primary endpoint):

o Target vessel failure (TVF) as defined above.

o Major Adverse Cardiac Events (MACE), patient oriented ( hierarchical order):

 All cause mortality.

 Any MI (including nontarget vessel territory)

 Any repeat revascularization (target and nontarget vessels) by means of CABG or PCI

o MACE, device/lesion oriented ( hierarchical order):

 Cardiac death

 MI not clearly attributable to a nontarget vessel

 Target lesion revascularization (TLR)

• Angiographic endpoints in entire population at final angiographic assessment :

o At final angiographic assessment the stented segment will be subdivided into 3 equally sized subsegments in which the individual minimum lumen diameter (MLD), reference diameter, percent diameter stenosis (% DS), mean lumen diameter will be determined. The ratio of the MLD to the predicted maximum balloon diameter, as determined from balloon charts provided by the manufacturer, will be calculated as a measure of radial force and potential immediate recoil of the stent. Angiographic endpoints will be assessed in the routine runes recorded during index PCI. The analysis requires no additional angiography runs.

• A substudy will include the following angiographic endpoints in subpopulation of patients referred for angiographic re-evaluation and in subpopulation of these patients who will require re-intervention e.g. clinically indicated angiographic re-evaluation:

o Intra-stent Late Lumen Loss (LLL) measured by QCA and defined as the difference between post-procedure minimal lumen diameter (MLD) and the subsequent angiography. (segment analysis)

o MLD, reference diameter, and %DS ( percent diameter stenosis; segment analysis)

o Angiographic evidence of stent thrombosis as outlined in table 7 of the appendix

• In subgroup of patients with clinically indicated Intravascular ultrasound (IVUS) the following endpoints will be assessed:

o In a subgroup of the patients with clinically indicated IVUS guidance of PCI, both conventional greyscale IVUS and virtual histology IVUS data sets will be analyzed from the IVUS runs that may be acquired before PCI, after the stent implantation, and finally at the end of the PCI procedure. These analyses will include measurements of minimal lumen cross-sectional area (CSA) and diameter, mean lumen CSA, adequacy of stent expansion, stent symmetry, adequacy of stent apposition, plaque prolapse, and stent-reference lumen area ratio [17].

o In the subgroup of patients with re-PCI for restenosis, the use of IVUS should be considered [18,19], which can help to adequately treat patients. In patients with stent thrombosis, the use of IVUS is strongly recommended, as it may be of critical importance in order to identify the mechanism of stent thrombosis and avoid recurrence of this adverse event. IVUS measurements will include the same as described above in the context of the index procedure with the addition of: measurement of mean neointima, lumen, and stent CSA and volume; in-stent percent volume obstruction; minimum and maximum neointima, lumen, and stent CSA, and minimum and maximum in-stent CSA obstruction; neointima, lumen and stent CSA at the site of the minimum in-stent lumen CSA; and the presence and the extent of late stent malapposition.