P2Y12 Inhibitors Utilization in Bifurcation and Chronic Total Occlusion PCI With Biologically Active Stents (P2BiTO) Registry
Conditions: Coronary Arteriosclerosis
Sponsor: G. d'Annunzio University

 
1 
Project Title:  
P2Y12 inhibitor utilization in Bifurcation and Chronic Total Occlusion percutaneous 
coronary intervention with biologically active stents (P2BiTO) registry. 
ClinicalTrials.gov Identifier: NCT01967615 
- Substudy on Bifurcations - 
 
WHAT IS ALREADY KNOWN ON THE SUBJECT  
The newer P2Y12 inhibitors (prasugrel and ticagrelor) were both associated with a significant 
reduction in the risk of adverse major events in patients undergoing percutaneous coronary 
interventions (PCI) and receiving aspirin in the setting of an acute coronary syndrome (ACS)1, 2. 
Such a benefit apparently occurs mostly through a reduction in the rate of stent thrombosis. 
Although independent clinical trials should be compared directly, the 1-year relative risk reduction 
(RRR) of definite of probable stent thrombosis3 in patients receiving a drug-eluting stent (DES) 
were fairly different in TRITON-TIMI 38 and PLATO, with a 67% (P<0.001) RRR for prasugrel1 
and a 10% (P=NS) RRR for ticagrelor2 – the latter RRR being reported as 25% (P=0.017) when 
taking into account all coronary stents, either previously implanted or inserted during the course of 
the trial4.  
The incidence of “biologically active” stent thrombosis is largely variable according to different 
platforms and lesion settings, being highest when metal struts are inadequately deployed, as after 
recanalization of a chronic total occlusion (CTO)5, in bifurcations – mostly after double DES 
implantation6, 7 – and after PCI with the recently available bioresorbable vascular scaffolds (BVS)8. 
The “P2Y12 inhibitor utilization in Bifurcation and Chronic Total Occlusion percutaneous 
coronary intervention with biologically active stents (P2BiTO) registry” has been designed with 
the aim to verify the translation of the supposed benefit of “newer” P2Y12 inhibitors in the setting 
of PCI with double overlapping DES or BVS in various clinical scenarios, where prasugrel and 
ticagrelor would be primarily prescribed in patients with an ACS, clopidogrel in patients with stable 
ischemic heart disease. 
The “Substudy on Bifurcations” of the P2BiTO registry aims to analyze the outcome of patients 
treated with single or multiple “biologically active” stents – either DES or BVS – for lesions 
located in coronary bifurcations, focusing on the relative implication of drugs, platforms and 
techniques on clinical outcomes. 
 
 
 

 
2 
WHAT 
DOES 
THE 
SUBPROJECT 
ON 
BIFURCATIONS 
ADD 
TO 
THE 
INFORMATION ALREADY AVAILABLE  
1. 
To obtain an up-to-date descriptive analysis (registry) of the real-world attitude of P2Y12 
inhibitors utilization for the management of patients with PCI of coronary bifurcation.  
2. 
To verify the translation of the postulated different reduction in the risk of “biologically 
active” stent thrombosis among various P2Y12 inhibitors (prasugrel and ticagrelor as compared 
with clopidogrel) in the treatment of a coronary bifurcation. 
3. 
To test the relative risk of adverse outcome for the various double stent techniques and to 
compare for each strategy the relative risk reduction obtained with newer P2Y12 inhibitors vs. 
clopidogrel. 
 
DETAILED DESCRIPTION OF THE PROJECT MAIN AND SECONDARY OBJECTIVES  
Data on all patients aged 18-80 who underwent PCI of a bifurcating lesion (all Medina6 types) 
with single or multiple “biologically active” stents (DES or BVS) at participating centers in 
the period January 2012 – December 2014 will be deemed eligible to enter the registry.  
PCI access site and technique will be recorded as left at operator’s discretion, as well as 
antithrombotic management. No limitation will be applied for the technique of PCI, for single or 
double DES or BVS (e.g. T-stenting, coulotte, crush and its modifications). 
Patients’ data will be entered on a common excel data sheet, and advancement of data collection 
and analysis will be shared among all study participant centers periodically during study progress.  
In-hospital outcomes will be recorded; all patients discharged alive will be followed up with a 30-
day and 6-month telephone interview and a 1-year visit. 
The primary end-point will be the occurrence of a cluster of major adverse cardiovascular 
events (MACE) at 1 year: 
a. 
Death from any cause. 
b. 
Myocardial infarction (MI). 
c. 
Stent thrombosis, defined as following the Academic Research Consortium3. 
The secondary endpoints will be: 
1. 
In-hospital MACE 
2. 
The single 1-year MACE (death, MI and stent thrombosis), as well as target vessel 
revascularization (TVR)  
3. 
Bleeding as defined by the Bleeding Academic Research Consortium (BARC)9. 
 
 

 
3 
STATISTICAL ANALYSIS AND CALCULATION OF THE SAMPLE SIZE 
The primary purpose of the data analysis will be to determine whether the 1-year probability of the 
occurrence of the primary end-point would significantly differ between patients undergoing newer 
P2Y12 inhibitors (either prasugrel or ticagrelor) as compared with clopidogrel. 
Sample size calculation has been based on the estimation of differences in the rates of occurrence of 
the primary endpoint between the two groups by use of the 2-sided Fisher exact test, with type I 
error at 5% and 80% power.  
Based on the adverse event rates recently reported by large registries on coronary bifurcations10, 11, 
and assuming a cumulative 1-year rate of MACE of 10%, an overall sample size of 1,422 patients in 
each group would allow to detect a reduction of 30% in the occurrence of the combined primary 
end-point among patients receiving the newer P2Y12 inhibitors as compared to clopidogrel. By 
estimating a 10% drop-off rate for incomplete data, data on 1,575 patients will have to be grouped 
in each arm and therefore a total of 3,150 patients will have to be screened in the study. 
 
GENERAL TRANSFERIBILITY AND POTENTIAL IMPACT OF RESULTS 
In the current cost-containment strategy, clopidogrel is still the most used P2Y12 inhibitor 
prescribed in patients undergoing PCI. Although both prasugrel and ticagrelor have shown a clinical 
benefit as compared to clopidogrel as adjunctive antiplatelet therapy among patients with ACS 
undergoing PCI, they are still underused in such clinical scenario. Currently, the use of newer 
P2Y12 inhibitors is off-label in stable coronary artery disease, and the present registry will obtain a 
picture of the attitude of physicians. 
The present registry gives a unique opportunity to monitor the actual utilization in the “real world” 
of newer P2Y12 inhibitors and to test their effectiveness in patients with high risk of “biologically 
active” stent (either DES or BVS) thrombosis. 
 

 
4 
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