The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and bivalirudin).
The HORIZONS-AMI Trial compared the effectiveness of heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin in acute myocardial infarction (AMI) patients undergoing stent deployment 1. Overall the data showed benefits associated with the bivalirudin treatment with lower rates of all-cause mortality, cardiac mortality, re-infarction and non-CABG related major bleeding; However, the data seems to indicate a non-significant increase in acute stent thrombosis in the bivalirudin group. This observation seems to suggest the potential benefits of adding an antiplatelet agent to bivalirudin. A study by Dangas G et al found that in the HORIZONS-AMI patients, the group receiving 600 mg loading-dose of clopidogrel had significantly lower 30-day unadjusted rates of mortality, reinfarction and stent thrombosis than the 300 mg loading-dose group, without increase in bleeding rate. Furthermore, even though the benefits of bivalirudin were independent of the clopidogrel loading dose; the 600mg LD was associated with more benefits with both anticoagulation regimens. Similar observations have been reported in the ARMYDA-6 MI study. It is our hypothesis that using ticagrelor instead of clopidogrel, given its more potent and faster activity, would have greater antithrombotic activity and therefore may reduce the rate of acute stent thrombosis when administered in combination with bivalirudin + ASA in AMI patients. To investigate this hypothesis, we will compare the antithrombotic effects of ticagrelor with clopidogrel, when administered in combination with ASA and bivalirudin, in healthy human volunteers using a cross-over study design. The antithrombotic activity will be assessed pre-treatment and 2-hours and 24-hours post treatment, using methodologies including Badimon Perfusion chamber, VerifyNow P2Y12 assay, platelet aggregation with Multiplate Analyzer and Thromboelastography.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Change in thrombus size at 1 hour as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
Time frame: Pre-treatment baseline and 1 hour
Platelet-thrombus Formation in an ex Vivo Model of Thrombosis
Change in thrombus size at 24 hours as compared to Pre-treatment baseline, where a positive change represents a decrease in thrombus size.
Time frame: Pre-treatment baseline and 24 hrs post treatment
Platelet Reactivity
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
Time frame: Pre-treatment baseline
Platelet Reactivity
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
Time frame: 1 hr post-treatment
Platelet Reactivity
Platelet reactivity measured by VerifyNowP2Y12 assay measuring percent inhibition
Time frame: 24-hours post-treatment
Blood Thrombogenicity
Coagulation times, assessed using the ROTEM thromboelastometry
Time frame: Pre-treatment baseline
Blood Thrombogenicity
Coagulation times, assessed using the ROTEM thromboelastometry
Time frame: 1 hr post-treatment
Blood Thrombogenicity
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Coagulation times, assessed using the ROTEM thromboelastometry
Time frame: 24-hours post-treatment