Differential Effect of Ticagrelor Versus Prasugrel on the Adenosine-induced Coronary Vasodilatory Responses in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Study Overview
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Brief Summary
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This is a prospective, randomized, single-blind, investigator-initiated, crossover study. Patients with Acute Coronary Syndrome (ACS) subjected to percutaneous coronary intervention (PCI), are randomized after informed consent, in a 1:1 ratio to either ticagrelor 90mg x2 or prasugrel 10mg x1 for 15 days. At Day 15± 2 days, coronary diastolic blood flow velocity in left anterior descending artery (LAD) is evaluated at baseline (bCBFV) and under 2 min adenosine infusions (maximal diastolic CBFV- maxCBFV) at gradually increasing doses of 50μg/kg/min, 80μg/kg/min, 110μg/kg/min and 140μg/kg/min with at least 5 min recovery intervals between infusions. A crossover directly to the alternate treatment is performed followed by the same evaluation at Day 30±2 days .

Official Title
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Differential Effect of Ticagrelor Versus Prasugrel on the Adenosine-induced Coronary Vasodilatory Responses in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Prasugrel
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-74 years Patients with acute coronary syndrome undergoing PCI with stenting Sinus rhythm Written informed consent Exclusion Criteria: Known hypersensitivity to prasugrel or ticagrelor Requirement for oral anticoagulant prior to the Day 30 visit Any previous history of ischemic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm) Any active bleeding or history of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months, other bleeding diathesis, or considered by investigator to be at high risk for bleeding Concomitant oral or IV therapy with strong CY P3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazana vir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin /rifampicin, phenytoin, carbamazepine). Increased risk of bradycardiac events. Dialysis required. Severe uncontrolled chronic obstructive pulmonary disease Known severe hepatic impairment Pregnancy or breastfeeding Left ventricular ejection fraction < 45%, severe left ventricular hypertrophy, diastolic dysfunction, severe valve disease Prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting Weight < 60 Kg Alcohol or narcotics abuse Major periprocedural complications: death, cardiogenic shock, stent thrombosis, arrhythmias requiring cardioversion/defibrillation, temporary pacemaker insertion or intravenous antiarrhythmic agents, respiratory failure requiring intubation, retroperitoneal bleeding, major bleeding (need for blood transfusion or drop in haemoglobin post-PCI by ≥ 5 gr/ dl or intracranial bleeding), unsuccessful PCI (residual stenosis > 30% or flow < ΤΙΜΙ 3) or planned staged PCI in the next 5 days after randomization Any residual stenosis > 40% in LAD Small vessels or diffuse coronary atherosclerosis Inability to detect coronary blood flow in LAD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prasugrel<br>Prasugrel 10mg/day for 15 days | Drug: Prasugrel<br>* Prasugrel 10mg/day for 15 days<br>|
| Experimental: Ticagrelor<br>Ticagrelor 90mg twice a day for 15 days | Drug: Ticagrelor<br>* Ticagrelor 90mg twice a day for 15 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the curve (AUC) of the maxCBFV (maximal diastolic blood flow velocity in left anterior descending artery)at gradually increasing doses of adenosine | The primary outcome will be assessed 15 days after the onset of each study drug | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 50μg/kg/min adenosine infusion at the end of treatment periods |  | 15 days | 
| The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 80μg/kg/min adenosine infusion at the end of treatment periods |  | 15 days | 
| The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 110μg/kg/min adenosine infusion at the end of treatment periods |  | 15 days | 
| The ratio of maximal diastolic blood flow velocity in left anterior descending artery/baseline diastolic blood flow velocity in left anterior descending artery for 140μg/kg/min adenosine infusion at the end of treatment periods |  | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ticagrelor, doppler echocardiography