Recalibrating Reperfusion Waypoints.

The realization that thrombus was the cause and not the consequence of acute myocardial infarction was a transformative pathophysiologic insight.1 An even more stunning observation was the subsequent discovery that restoration of coronary patency could salvage ischemic myocardium and improve clinical outcomes in ST-elevation acute myocardial infarction (STEMI).2,3 Assertive clinical investigations of both the content and process of STEMI care over the subsequent 4 decades has demonstrated that the ultimate success of reperfusion is modulated by the timeliness, efficiency, and efficacy with which it is applied. Whereas contemporary guidelines indicate that primary percutaneous coronary intervention (PCI) is the preferred strategy for STEMI, most patients with STEMI do not present to a primary PCI (PPCI) center, and ≈50% are walk-ins who do not utilize emergency medical services.4–6 Accordingly, persisting delays—attributable to both patients and the healthcare system—in achieving timely PCI (ie, within 60 to 90 minutes of symptoms to first medical contact) are common and exact a price of excess morbidity and mortality.7,8 Advances in fibrinolytic, anti-thrombotic, and antiplatelet therapies, coupled with improved preand in-hospital systems of care, have evolved dramatically pari passu with these clinical realities. Accumulating contemporary evidence indicates that early fibrinolytic therapy followed by timely PCI, where appropriate, achieves clinical outcomes at least as good as PPCI in the common circumstance, where delay to PPCI is >60 to 90 minutes from first medical contact.9,10 In this issue of Circulation, 11 the EARLY-MYO trial (Early Routine Catheterisation After Alteplase Fibrinolysis Versus Primary PCI in Acute ST-Elevation Myocardial Infarction) investigators provide another waypoint to help navigate the continuing reperfusion journey. Using a noninferiority design, they targeted a composite reperfusion end point of both thrombolysis in myocardial infarction flow and perfusion grade 3 combined with ST segment resolution ≥70% after PCI.11 They randomized 344 low-risk East Asian patients with STEMI ≤6 hours of symptom onset to either a pharmaco-invasive (PhI) strategy with half-dose alteplase or PPCI and found the primary end point to be 34.2% versus 22.8% for PhI versus PPCI, respectively (P<0.05 for noninferiority and P=0.022 for superiority). Given that the angiographic end point was after PCI and the ST segment resolution assessment was ≈60 minutes after PCI in both treatment groups, it can be argued that this later assessment of reperfusion in the PhI group (≈7 hours after the PPCI group) Recalibrating Reperfusion Waypoints