Routine angioplasty after fibrinolysis--how early should "early" be?

Reperfusion therapy has represented a great leap forward in the management of myocardial infarction with ST-segment elevation. Its goal is early and complete recanalization of the infarct-related artery to salvage myocardium and improve both early and late clinical outcomes. Complete reperfusion can be achieved with either fibrinolysis or primary percutaneous coronary intervention (PCI), but with primary PCI the success rate is higher than 90%, whereas current fibrinolytic therapy leads to full reperfusion in only 50 to 55% of recipients. Primary PCI, therefore, looks like the most appropriate reperfusion tool, but there are substantial logistic restrictions associated with it. The door-to-balloon time with primary PCI is typically longer than the time within which inhospital fibrinolytic therapy can be initiated, and primary PCI requires a network of dedicated ambulances and emergency departments to shorten the door-to-balloon time as much as possible.1,2 Primary PCI is an especially attractive strategy in the United States, where nearly 80% of the adult population lives within 1 hour’s drive of a PCI center.3 Investigators have tried to combine the best of both therapies by performing PCI immediately after fibrinolysis. The concept of fibrinolysis followed immediately by PCI (termed facilitated PCI) seems attractive: early reperfusion with the use of a widely available strategy to salvage as much myocardium as possible, followed by PCI to ensure both reperfusion in the case of fibrinolytic failure and prevention of recurrent thrombosis that may result in reocclusion and reinfarction. Studies of PCI performed immediately after fibrinolysis were initiated in the late 1980s, but a meta-analysis in 2005 showed that this approach was not usually beneficial,4 probably in part because of the use of outdated fibrinolytic and antiplatelet regimens and PCI equipment in those studies but also because of the increased risk of bleeding. The latter concern, especially, made many interventional cardiologists reluctant to intervene after fibrinolysis, although the results of a trial of rescue PCI after failed fibrinolysis suggest that this procedure is effective and relatively safe.5 Since the major problem with the combination of fibrinolytic therapy with immediate PCI is thought to be the short interval between fibrinolysis and PCI, some later studies have investigated the outcome when a longer interval is used. Besides reducing the risk of bleeding, this approach enables the transfer of patients from centers that do not have the capability of performing PCI (where initial fibrinolysis is performed) to a PCI center. These studies showed that the approach was successful; however, the sample sizes in the studies were relatively small.6-9 In this issue of the Journal, Cantor et al. report the results of the Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI; ClinicalTrials.gov number, NCT00164190), a large study on this topic.10 More than 1000 Canadian patients with myocardial infarction with ST-segment elevation who were treated with fibrinolysis were randomly assigned to interhospital transfer for intended routine early PCI (within 6 hours after fibrinolysis) or an ischemia-guided strategy, in which patients were transferred for angiography only in the case of failed fibrinolysis or of recurrent ischemia. As in the four smaller trials, the rate of recurrent ischemia was significantly reduced with early routine PCI as compared with a selective invasive approach. Given the sample size and the study design, and with little evidence to