Pharmacodynamic and Pharmacokinetic Profiles on Switching From Cangrelor to Prasugrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: The Switching Antiplatelet -6 (SWAP-6) Study
Phase: PHASE4
Conditions: Coronary Artery Disease, Acute Coronary Syndrome
Sponsor: University of Florida

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Pharmacodynamic and pharmacokinetic profiles on switching from cangrelor to prasugrel 
in patients with acute coronary syndrome undergoing percutaneous coronary intervention: 
The Switching Antiplatelet -6 (SWAP-6) study 
 
 
 
 
 
 
 
 
Francesco Franchi, MD 
Assistant Professor of Medicine 
Division of Cardiology 
University of Florida College of Medicine - Jacksonville 
655 West 8th Street 
Jacksonville, FL – 32209 
Tel: +1-904-244-2060, Fax: 904-244-3102 
francesco.franchi@jax.ufl.edu 
 
 
 
 

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PROJECT SUMMARY 
Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet 
inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing 
coronary stenting. Although in this setting the potent oral P2Y12 inhibitor prasugrel is 
commonly utilized, there is very limited data on the optimal approach for switching between 
these therapies. In particular, ruling out a drug-drug interaction (DDI) is critical to this extent as 
the presence of a DDI would translate into reduced or abolished antiplatelet effects exposing 
these acute patients to an increased thrombotic risk. There is an unmet need to better elucidate 
pharmacodynamic profiles associated with the transition from cangrelor to prasugrel therapy. Of 
note, prasugrel has recently gone off patent and the availability of a generic formulation will 
favorably impact its use. Pharmacodynamic studies provide some support on the safety of 
administering prasugrel at the start of cangrelor infusion. However, the available data does not 
allow to rule out a DDI given that there was no comparator arm in which prasugrel was either 
given alone or at the end of cangrelor infusion. The methodological approach for this assessment 
should rely on comprehensive pharmacodynamics investigations aimed to assess levels of P2Y12 
receptor inhibition, pharmacokinetic investigations to assess systemic levels of the drug/drug 
metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene 
expression. The overarching aim of this investigation is to rule out a DDI when cangrelor and 
prasugrel are concomitantly administered in patients undergoing coronary stenting. 

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BACKGROUND 
Cangrelor is an intravenous adenosine triphosphate (ATP) analogue that directly and 
reversibly inhibits ADP binding to the adenosine diphosphate (ADP) P2Y12 receptor subtype in a 
dose-dependent manner, achieving immediate potent platelet inhibition after a bolus dose [1,2]. 
The cangrelor binding site at the P2Y12 receptor level has been subject to controversy and is not 
clearly defined [3,4]. Nonetheless, cangrelor is associated with high levels of receptor occupancy 
and prevents ADP binding. Cangrelor is promptly inactivated through dephosphorylation by 
ectonucleotidase and has a very short plasma half-life (3-6 minutes) [1-4]. Therefore, recovery of 
platelet function is rapid (~60 minutes) after discontinuation of cangrelor infusion [1-4].  
Cangrelor was approved for clinical use based on the results of the CHAMPION 
(Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) 
PHOENIX trial, which showed that cangrelor significantly reduced the rate of ischemic events, 
driven by a reduction in stent thrombosis and myocardial infarction, with no significant increase 
in severe bleeding in patients undergoing percutaneous coronary intervention (PCI) [5]. Given 
the different pharmacological properties of cangrelor and the oral P2Y12 inhibitors, several 
studies have investigated the potential for drug-drug interaction (DDI) when these agents are 
concomitantly administered [6-12]. These potential DDI are concerning as they can result in 
reduced platelet inhibition and subsequent lack of protection from thrombotic complications in 
the peri-PCI period. In a study conducted in healthy volunteers, clopidogrel administration 
during cangrelor infusion was associated with an impaired antiplatelet effect of clopidogrel after 
cangrelor discontinuation [6]. This reflects the fact that clopidogrel active metabolite cannot bind 
to the P2Y12 receptors if already largely occupied by cangrelor. In turn, the plasma 
concentrations of the unbound clopidogrel active metabolites fall rapidly to subtherapeutic levels 

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as a result of distribution to other compartments and systemic clearance. Therefore, after 
stopping cangrelor infusion, when receptors become available for binding, most of the active 
metabolite has already been eliminated from the circulation [6]. In contradistinction, 
clopidogrel’s antiplatelet effects are not diminished when it is administered after cangrelor 
infusion, because of the very fast offset of action of cangrelor and subsequent availability of 
P2Y12 receptors for binding by clopidogrel active metabolite [6]. Accordingly, across the 
CHAMPION clinical trial program, a clopidogrel loading dose (LD) was administered always 
immediately after discontinuation of cangrelor infusion [5,13-15]. 
Although cangrelor was approved based on a trial in which clopidogrel was used, in real-
world clinical practice cangrelor is more commonly utilized in high-risk patients undergoing 
PCI, in whom the newer generation P2Y12 inhibitors (i.e, prasugrel and ticagrelor) are 
recommended over clopidogrel [16,17,18]. Recommendations on how to transition from 
cangrelor to oral treatment with ticagrelor and prasugrel largely derive from pharmacodynamic 
(PD) studies [3,4,8,9]. Unlike that observed with clopidogrel, no interaction was shown when 
transitioning from cangrelor to ticagrelor, allowing for a more versatile use of ticagrelor with 
respect to timing of administration in relation to the start of cangrelor therapy [8]. The presence 
of an interaction between clopidogrel and cangrelor, but not between ticagrelor and cangrelor is 
probably the result of different half-lives of these drugs, as well as the different sites and types of 
binding to the P2Y12 receptor [3,4,6-8,11,12]. Ticagrelor reversibly binds the P2Y12 receptor at a 
site distinct from the ADP-binding site and has a half-life of 6-12 hours. Although it is unknown 
whether ticagrelor can bind with the P2Y12 receptor during cangrelor infusion, its half-life 
(which exceeds that of the duration of cangrelor infusion) is such that drug is still systemically 
available to bind with the P2Y12 receptor after discontinuation of cangrelor infusion [3,4,8]. 

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Based on these observations, ticagrelor can be administered before, during, or after cangrelor 
infusion [3,4,8]. 
The transition from cangrelor to prasugrel is associated with transient recovery of platelet 
reactivity, in particular within 1 hour after cangrelor discontinuation, which could be explained 
by a DDI similar to that described for clopidogrel [9]. However, it was observed that recovery of 
platelet function was attenuated when prasugrel was administered 30 minutes before stopping the 
cangrelor infusion [9]. Accordingly, it is recommended that prasugrel be administered at the end 
of cangrelor infusion or 30 minutes prior to discontinuation of infusion [3,4,9]. However, 
recently the ExcelsiorLOAD2 (Impact of Extent of Clopidogrel-Induced Platelet Inhibition 
during Elective Stent Implantation on Clinical Event Rate - Advanced Loading Strategies) study 
showed that prasugrel 60 mg LD given at the start of a 2-hour infusion of cangrelor was 
associated with sufficient platelet inhibition post-cangrelor, with only rare cases of high platelet 
reactivity (HPR) [19]. Moreover, there were no differences with levels of platelet reactivity and 
HPR rates compared with those observed with ticagrelor, which was also given at the start of the 
cangrelor infusion. These observations may be attributed to relatively higher concentration and 
longer half-life of prasugrel’s active metabolite compared with that of clopidogrel [20-23]. 
However, ExcelsiorLOAD2 was not powered to test the non-inferiority on PD effects between 
prasugrel and ticagrelor, but only for the comparison of prasugrel versus clopidogrel. Moreover, 
whether similar findings would be observed with longer infusions of cangrelor (e.g., up to 4 
hours) is unknown. Therefore, although the PD results of this study provide some support on the 
safety of administering prasugrel at the start of cangrelor infusion, the trial design does not allow 
to rule out a DDI given that there was no comparator arm in which prasugrel was either given 
alone or at the end of cangrelor infusion [24]. Moreover, pharmacokinetic (PK) assessments, 

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pivotal to help elucidate a DDI, were not performed. Accordingly, recommendations on timing 
of prasugrel administration in cangrelor treated patients remain unchanged.   
 
STUDY RATIONALE 
Guidelines recommend the preferential use of new generation P2Y12 inhibitors, including 
prasugrel, over clopidogrel in high-risk patients with coronary artery disease (CAD) undergoing 
PCI [16-18]. Since high-risk patients undergoing PCI is a setting in which cangrelor is frequently 
used, there is an unmet need to better elucidate PD profiles associated with the transition from 
cangrelor to prasugrel therapy. To date the uptake of the newer oral P2Y12 inhibitors has been 
mostly limited by costs. However, prasugrel has recently gone off patent and the availability of a 
generic formulation will favorably impact its use. Moreover, to date PD studies assessing the 
transition from cangrelor to prasugrel have been conducted in patients with stable coronary 
artery disease, and current recommendations are based on assessments conducted in patients not 
undergoing PCI [9]. Importantly, acute coronary syndrome (ACS) and PCI are both known to 
affect PK and PD profiles of antiplatelet agents. Overall, these observations strongly underscore 
the need to conduct dedicated investigations to rule out a DDI when transitioning from cangrelor 
to prasugrel and to define the optimal approach for transitioning therapy in real-world high-risk 
patients, including ACS patients, undergoing PCI. The methodological approach for this 
assessment should rely on comprehensive PD assessments aimed to assess levels of P2Y12 
receptor inhibition, PK assessments to assess systemic levels of the drug/drug metabolite, and 
mechanistic assessments by measuring levels of P2Y12 receptor gene expression. In particular, 
different levels of P2Y12 receptor gene expression can modulate the PD effects of oral P2Y12 
receptor inhibitors at a given level of drug exposure defined by PK profiling. 

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STUDY AIM 
The aim of this investigation is to rule out a DDI when cangrelor and prasugrel are 
concomitantly administered in high-risk patients undergoing coronary stenting. 
 
REASERCH PLAN 
Study design 
The Switching Antiplatelet Therapy-6 (SWAP-6) study will be a prospective, 
randomized, open label PD and PK study conducted in high-risk patients undergoing PCI. 
Patients presenting with a non-ST-segment elevation ACS (NSTE-ACS), including unstable 
angina (UA) and NSTE-myocardial infarction (NSTEMI), or with stable CAD but deemed at 
high risk undergoing an invasive management strategy as part of their standard of care will be 
screened. The study will be performed at the Division of Cardiology of University of Florida 
Health, Jacksonville, Florida. Patients will be screened by Cardiology Research staff, who will 
verify that all candidates meet inclusion and exclusion criteria, and obtain their written informed 
consent to participate in the study prior to undergoing their diagnostic invasive evaluation to 
define coronary anatomy. Results from blood tests performed within the last 90 days will be 
considered valid for screening purposes. If these are not available, a blood sample will be 
collected for the screening phase. 
After undergoing invasive diagnostic evaluation of coronary anatomy, patients 
undergoing PCI will be considered eligible for randomization. Using a computer-based 
randomization system, patients will be randomized in a 1:1:1 fashion to one of the following 
treatment arms: a) prasugrel only administered at the start of PCI (group 1); b) cangrelor plus 
prasugrel concomitantly administered at the start of PCI (group 2); c) cangrelor administered at 

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the start of PCI plus prasugrel administered at the end of the cangrelor infusion (group 3). 
Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg 
daily maintenance dose started 24 hours after LD administration [25]. Cangrelor will be used at 
the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion [26]. 
Study drugs will be administered before passing of the guidewire. The duration of cangrelor 
infusion will be 2 hours or until the end of PCI (whichever is longer). All patients will be on a 
background of aspirin therapy (325 mg loading dose followed by 81 mg daily maintenance 
dose). Patients will be managed according to standard of care. The interventional procedure will 
also be performed according to standard of care with choice of anticoagulant (heparin or 
bivalirudin) at the discretion of the operator. PK and PD assessments will be conducted at 7 time 
points: baseline, 30 minutes after administration of randomized treatment, end of PCI (defined as 
when the guide catheter is removed at procedure completion), 1 hour, 2 hours, 3 hours and 4 
hours after administration of randomized treatment. Figure 1 illustrates the overall study design. 
In patients in which the infusion will be maintained for more than 2 hours (until the end of PCI), 
the 3-hour and 4-hour after time points will be collected 1 hour and 2 hours after stopping 
cangrelor, respectively. 
Although the study will have an open-label design, laboratory personnel will be blinded 
to treatment assignments. During hospital stay, major adverse cardiac events (death, myocardial 
infarction, stroke, and urgent revascularization procedures), serious adverse events (bleeding and 
other adverse events), as well as non-serious adverse events considered to be study related will 
be collected. After completing the study, decisions on medical management, including the choice 
and duration of antiplatelet therapy will be at the discretion of the treating physician.   
 
 

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Figure 1. Overall study design 
 
 
 
 
Study Population 
Inclusion criteria: 
• Patients with NSTE-ACS (UA or NSTEMI) or high-risk patients with stable CAD 
undergoing PCI. NSTE-ACS will be defined as the presence of cardiac ischemic 
symptoms with ischemic changes (but not ST-segment elevation) on electrocardiogram 
with or without a positive troponin. However, normal electrocardiograms will be 
acceptable if the investigator will consider an ACS presentation likely. High-risk CAD 
will be defined at the discretion of the operator performing coronary intervention. 
• Age between 18 and 75 years old 
 
Exclusion criteria:        
• Inability to provide written informed consent 

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• Age >75 years 
• Weight <60 Kg 
• ST-segment elevation myocardial infarction 
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, 
ticagrelor) in past 7 days  
• Known allergies to prasugrel or cangrelor 
• Considered at high risk for bleeding 
• History of ischemic or hemorrhagic stroke or transient ischemic attack 
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban, 
apixaban, edoxoban) 
• Planned treatment with glycoprotein IIb/IIIa inhibitors (only bailout use allowed) 
• Fibrinolytics within 24 hours 
• Known platelet count <80x106/mL 
• Known hemoglobin <10 g/dL 
• Active bleeding 
• Known end stage renal disease on hemodialysis 
• Known severe hepatic dysfunction 
• Intubated patients (prior to randomization) 
• Pregnant females [women of childbearing age must use reliable birth control (i.e. oral 
contraceptives) while participating in the study] 
 
 
Blood sampling and Laboratory assessments 
Blood samples (10 mL) will be drawn through the arterial access sheet used for the PCI 
procedure for time points  while patient are in the cath lab (until the end of PCI); post-cath lab 
samples will be drawn through venous sampling. Samples will be collected in anticoagulated and 
serum tubes at each study time point for all PD and PK assessments. The first 2-4 mL of blood 
will be discarded to avoid spontaneous platelet activation. 

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Laboratory assessments will include the following: 
1. VerifyNow PRU assay 
2. VASP-PRI assay 
3. Total Thrombus-Formation Analysis System (T-TAS) 
4. PK 
5. P2Y12 gene receptor level expression 
 
Description of laboratory assays 
1) VerifyNow PRU: The VerifyNow System is a turbidimetric based optical detection system 
which measures platelet induced aggregation as an increase in light transmittance (Accriva, San 
Diego, CA) and will be utilized according to manufacturer’s instructions, as previously described 
[27-30]. The assay is based on microbead agglutination and uses specific reagents for the 
pathways of interest. The VerifyNow PRU assay, by combining ADP+PGE1, measures changes 
in platelet function specific to P2Y12 receptor inhibitors. The assay is based upon the ability of 
activated platelets to bind fibrinogen. Fibrinogen-coated microparticles aggregate in proportion 
to the number of GP IIb/IIIa receptors expressed. Microbead aggregation is more rapid and 
reproducible if platelets are activated; therefore the reagents are incorporated into the assay 
channel to induce platelet activation without fibrin formation. Light transmittance increases as 
activated platelets bind and aggregate fibrinogen-coated beads. The instrument measures this 
change in optical signal and reports results in P2Y12 Reaction Units (PRU). 
2) Whole blood vasodilator-stimulated phosphoprotein (VASP):  VASP phosphorylation (VASP-
P) is a marker of P2Y12 receptor signaling. VASP will be assessed the ELISA VASP-P kit 
(Biocytex Inc., Marseille, France) as previously described [31-33]. After a first step of parallel 

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whole blood sample activation with PGE1 and PGE1+ADP, platelets from the sample are lysed, 
allowing released VASP to be captured by an anti-human VASP antibody, which is coated in the 
microtiter plate. Then, a peroxidase-coupled anti-human VASP-P antibody binds to 
phosphorylated serine 239 antigenic determinant of VASP. The bound enzyme peroxidase is 
then revealed by its activity on TMB substrate over a predetermined time. After stopping the 
reaction, absorbance at 450 nm is directly related to the concentration of VASP-P contained in 
the sample.PGE1 increases VASP-P levels by stimulation of adenylate cyclase. Binding of ADP 
to P2Y12 leads to Gi-coupled inhibition of adenylate cyclase. Therefore, the addition of ADP to 
PGE1-stimulated platelets reduces PGE1-induced VASP-P levels. If P2Y12 receptors are 
successfully inhibited, addition of ADP will not reduce the PGE1-stimulated VASP-P levels. The 
platelet reactivity index (PRI) will be calculated after measuring VASP-P levels. 
3) Total Thrombus-Formation Analysis System (T-TAS): T-TAS is an automated microchip flow 
chamber system for the quantitative analysis of the thrombus formation process under blood flow 
conditions. T-TAS allows measurement of thrombus formation using the PL-chip (Diapharma, 
West Chester Township, OH) [34]. The PL-chip contains 25 capillary channels (width 40 μm, 
depth 40 μm) coated with type I collagen and is specifically designed for quantitative analysis of 
platelet thrombus formation, including platelet adhesion and aggregation, granule secretion, and 
thrombus growth in the absence of coagulation and fibrinolysis systems. In measurements using 
the PL-chip, a blood sample collected in a hirudin containing blood sampling tube. The platelet 
aggregates gradually increase in size and, in the process, occlude the capillary, resulting in an 
increase in flow pressure. In the present study, total platelet-derived thrombogenicity is 
expressed as the area under the flow pressure curve for the first 10 min for the PL-chip tested at a 

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flow rate of 18 μL/min (PL18-AUC10). Low PL18-AUC10 reflect reduced thrombus growth and 
rapid breakdown of the thrombus. 
 
3) Pharmacokinetic (PK) assay: Determination of prasugrel’s active metabolite concentration in 
plasma will be performed using liquid chromatography with tandem mass spectrometry 
according to standard protocols as previously described [27,35]. Blood will be drawn into 
standard EDTA tubes and within 30 seconds a derivatizing agent (3’-methoxyphenacylbromide) 
will be added to capture and stabilize the active metabolite. The geometric mean area under the 
concentration-time curve through the sampling time of the last quantifiable prasugrel’s active 
metabolite concentration (AUC[0-tlast]) will be calculated and the maximum observed plasma 
concentration (Cmax) and time to Cmax (Tmax) of Pras-AM will be recorded. 
4) P2Y12 gene receptor level expression: Gene expression in platelets will be performed using 
standard protocols. In particular, purified platelets are dissolved in Trizol reagent (Invitrogen) 
and total RNA will be extracted using RNA minipres kit (Zymos research) according to 
manufacturer’s protocol.  P2Y12 mRNA expression will be measured with real-time PCR using 
SYBR green and specific primers as previously described [36].   
 
Study endpoints, sample size calculation and statistical analysis 
 
The primary end point of the study will be the non-inferiority in PRU measured at 4 
hours of cangrelor plus prasugrel concomitantly administered at the start of PCI versus prasugrel 
only administered at the start of PCI (group 2 vs. group 1). Non-inferiority will be assessed using 
a 95% confidence interval (CI) of the difference in mean PRU between the two arms. Under the 
assumption of 0 difference in mean PRU between group 1 and group 2 and a common standard 

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deviation of 50 PRU, a sample size of 22 patients per group will allow for the 95% CI to stay 
within ± 45 PRU with a 90% power and alpha=0.05. Considering a 25% data attrition rate due to 
GPI use, hemolysis, drop out or technical problems, 28 patients per group will need to be 
randomized in order to ensure complete available data for analysis. Considering the 3 arms of 
treatment up to 84 patients will need to be randomized. The sample size of this study was 
established according to results of previous PD investigations [28,37]. In line with previously 
reported investigations, 45 PRU was chosen for the noninferiority margin for the upper 95% CI 
limit of the difference [29,30]. Group 3 will be included in study design as this strategy 
represents current standard of care for the transition from cangrelor to prasugrel. However, the 
study will be powered to assess non inferiority of group 2 vs. group 1. Therefore, all other end 
points will be considered exploratory and will include the comparisons of PD and PK 
parameters, and P2Y12 gene receptor level expression between all treatment arms at each time 
points, as well as the comparisons of rates of high on-treatment platelet reactivity (HPR). HPR 
will be defined as PRU>208 and PRI>50%, in line with consensus definitions [38].  
Conformity to the normal distribution will be evaluated for continuous variables with the 
Kolmogorov-Smirnov test. For baseline characteristics, continuous variables will be expressed as 
mean ± SD or median [IQR]. One-way analysis of variance or Kruskal-Wallis test will be used to 
compare continuous variables. Chi-squared test will be used to compare categorical variables 
among groups. An analysis of covariance (ANCOVA) method with a general linear model, with 
treatment as the main effect and baseline values of platelet reactivity as a covariate, will be used 
to evaluate the primary end point as well as all between-group comparisons at each time point. 
Least-square mean (LSM) differences in PRU between group 1 and group 2 and the 
corresponding 2-sided 95% CI for the difference will be obtained to assess non-inferiority based 

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on the ANCOVA model. Given the exploratory nature of comparisons for secondary end points, 
correction for multiple comparisons will not be performed. A 2-tailed p value of <0.05 will be 
considered to indicate a statistically significant difference for all the analyses performed. 
Statistical analysis will be performed using SPSS version 22.0 software (SPSS Inc., Chicago, 
Illinois).  
The safety population will include all randomized patients exposed to study medication. 
The PD population will include all patients with PD data and without a major protocol deviation 
thought to affect significantly the PD and PK of cangrelor or prasugrel. The PD population will 
be used for analysis of all primary and secondary end points. Erroneously treated patients (eg, 
those randomized to one treatment but actually given the other) will be accounted for based on 
the actual treatment received. 
 
Publication Strategy/Additional Information  
Subjects will be identified with a number and data collection sheets will all be stored in a 
locked area. Data will be kept for 6 years after enrollment ends to comply with HIPAA 
regulations. Patients will receive a handout with the names and telephone numbers of the doctors 
involved in the study. Study subjects will be identified first (months 1-17): we expect to 
randomize 5 subjects monthly and complete enrollment in 17 months (total: 84 subjects 
randomized). Months 18-20 will be implied for statistical analysis and manuscript preparation. 
Results will be presented at the first available major cardiovascular meeting (e.g. AHA, ACC, 
ESC), and final manuscript will be submitted to publication to one of major cardiovascular 
journals (e.g. JACC, Circulation, European Heart Journal). 
 

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Possible Discomforts and Risk 
In clinical trials, the most common clinical side effect of cangrelor was bleeding. 
Severe/moderate bleeding occurred in 0.8% of patients receiving cangrelor, as compared to 0.6% 
of those receiving placebo. Other side effects include dyspnea (1.3%), worsening renal function 
(3.2% of patients with severe renal impairment), and hypersensitivity (0.05%) [5]. In clinical 
trials, the most common clinical side effects of prasugrel were blurred vision, dizziness, 
headache, nervousness; infrequent events included intracranial hemorrhage (0.79%) and severe 
neutropenia (< 0.1%). The most important adverse effect associated with the use of prasugrel is 
bleeding (2.4%) [39]. However, both cangrelor and prasugrel are standard of care therapies and 
would be potentially utilized as part of standard of care treatment in this study. 
All clinical events described above, if they were to occur, as well as death, myocardial 
infarction, stroke, and urgent revascularization procedure with PCI or coronary artery bypass 
grafting will be recorded. Bleeding data will be collected using BARC definitions [40]. Clinical 
events will be evaluated by a local committee, comprised of 2 faculty members (2 cardiologists), 
not directly involved in the research. In the event of a report of a serious adverse event the local 
committee will meet and antiplatelet treatment management will be managed according to 
physician recommendation. 
 
Conflict of Interest 
Dr. Angiolillo (Sub-Investigator) is a consultant for Chiesi, the maker of cangrelor. 
 
 

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