2,3 This approach should not to be confused with facilitated PCI where thrombolysis (full- Ibrutinib clinical trial or half-dose) is followed by immediate pre-planned PCI to mitigate the delay associated with PCI. The latter strategy, while being intuitively appealing, is not recommended owing to increased risk of adverse events including death, intracranial hemorrhage, and paradoxically,

ischemic events (likely due to fibrinolysis-induced platelet activation). 4,5 Data from the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial 6 and 5-year results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 7 provide further evidence on the effectiveness and safety of a pharmacoinvasive approach. Stream Trial This open-label, multicenter, prospective, randomized trial was designed to test whether fibronlytic therapy – administered before arrival to hospital, or early after admission – coupled with early coronary angiography provides outcomes similar to PPCI in patients presenting with acute STEMI. Patients were eligible for enrollment if they presented within 3 hours from onset of symptoms, had evidence of acute STEMI on their initial electrocardiogram (ECG), and were unable to undergo primary PCI

within one hour after the first medical contact (FMC). Over a period of 4 years, 1915 patients were enrolled from 99 sites in 15 countries. 1892 ultimately underwent randomization (81% in the ambulance setting) to either receiving tenecteplase along with antiplatelet and anticoagulant therapy, followed by coronary angiography within 6–24 hours (pharmacoinvasive

group) or to primary PCI (PPCI group). According to the investigator’s judgment, urgent coronary angiography (and PCI when appropriate) in the pharmacoinvasive group was allowed at any stage in the presence of hemodynamic or electrical instability, worsening ischemia or sustained/progressive ST-segment elevation. The primary end-point was a composite of death from any cause, shock, congestive heart failure or reinfarction at 30 days. Safety end-points included ischemic stroke, intracranial and non-intracranial hemorrhage bleeding. Upon the advice of the data and safety monitoring board, the trial Carfilzomib protocol was amended after 21% of the study population had been enrolled: the dose of tenecteplase was reduced by 50% in patients 75 years of age or older because of an excess rate of intracranial hemorrhage observed in that group. At 30 days, the primary end-point occurred in 116 patients (12.4%) in the pharmacoinvasive group and 135 patients (14.3%) in the PPCI group (relative risk in the pharmacoinvasive group, 0.86; 95% CI, 0.68–1.09; p = 0.21).