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

• Status: Completed
• Trial end date: 2012-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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 .

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Patras
• Treatments: Adenosine; Prasugrel Hydrochloride; Ticagrelor

Criteria

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