differential effect of ticagrelor versus prasugrel on the adenosine-induced coronary vasodilatory responses in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Conditions: Acute Coronary Syndrome

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 .


Eligibility 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

Keywords: ticagrelor doppler echocardiography