LAUSR

ST‐segment elevation myocardial infarction (STEMI) typically results from a total thrombotic occlusion following a ruptured atherosclerotic plaque. Early recognition and rapid reperfusion with percutaneous coronary intervention (PCI) are critical to salvage myocardium and prevent subsequent morbidity and mortality. Periprocedural antiplatelet and antithrombin inhibitors are crucial to prevent PCI‐related complications, including stent thrombosis (ST). In 2010, we reported a significant improvement in infarct‐related artery patency and reduction in reinfarction and ST in STEMI patients pretreated with clopidogrel in a large regional STEMI system. Pretreatment duration of >60min led to a reduction in 30‐day reischemia/reinfarction (1.0% vs. 2.9%, p = 0.003) with no increase in bleeding. New generation P2Y12 inhibitors, ticagrelor, and prasugrel, are more potent with more consistent activity and faster onset. The only multi‐center randomized clinical trial (ATLANTIC) to assess the impact of prehospital ticagrelor administration, failed to meet the coprimary endpoint of Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct‐related artery before PCI. Bleeding risks were similar between pre‐ and in‐hospital ticagrelor; however, there was no difference in the composite endpoint of death, MI, stroke, urgent coronary revascularization, or ST. However, the trial enrolled a selected low‐risk STEMI population with only a 31‐min median difference between the pre‐ and in‐hospital ticagrelor administrations —likely insufficient time for effective platelet inhibition given the average 30‐min to 4‐h onset of action with ticagrelor. A recent comprehensive meta‐analysis, including seven randomized clinical trials, concluded that pretreatment with P2Y12 inhibitors (any time before arrival in the cardiac catheterization laboratory [CCL]) significantly reduced major adverse cardiovascular events by 27% and improved pre‐PCI TIMI flow grade by 12% compared with delayed treatment (any time after arrival in the CCL) with no difference in bleeding risk. Post hoc analyses of prospective registries have reported conflicting results on clinical endpoints but always without increased bleeding risk. Given the diverse evidence from the experimental and observational studies, the national guidelines do not provide specific timing for P2Y12 inhibitors but recommend the administration “as early as possible.” In this issue of Catheterization and Cardiovascular Interventions, Fabris et al. present a pre–post protocol quality initiative study between January 2018 to September 2020 in northeast Italy. A novel pretreatment protocol was initiated in a single tertiary STEMI center that included heparin bolus (70 UI/kg or max 5000UI), aspirin (lysine salicylate 250mg IV), and a loading dose of oral ticagrelor (180mg) at the first medical contact. Before the pretreatment protocol, only aspirin (lysine salicylate 250mg IV) was administrated at the first medical contact, while a heparin bolus (70 UI/kg or max 5000UI) and a loading dose of any P2Y12 inhibitor were administrated in the CCL. A total of 537 consecutive STEMI patients were enrolled in the study, including 300 in the preintervention and 237 in the postintervention groups. Of note, 23.2% of the postintervention participants actually did not receive pretreatment but were treated in the CCL. Given the relatively high noncompliance, the authors present both per‐protocol and intention‐to‐treat analyses. In the intention‐to‐treat analysis, baseline characteristics, clinical features, angiographic findings, and ischemia times were comparable between pre‐ and postintervention groups other than less hypertension in the postintervention group. The median difference time for antithrombotic administration between the pre‐ and postintervention groups was 78min (interquartile range: 61–101). The primary endpoint of