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Providence, RI
Dr. Wu is Assistant Professor of Medicine at Brown Medical School. Dr. Gordon is Director, Cardiac Catheterization Laboratory and Coronary Care Unit, The Miriam Hospital.
Correspondence to: Wen-Chih Wu, MD, Division of Cardiology, Veterans Affairs Medical Center, 830 Chalkstone Ave, Providence, RI 02908; e-mail: wen-chih_wu{at}brown.edu
Enormous steps have been taken in the care of patients with acute myocardial infarction (AMI). Specifically, the advent of early reperfusion with either thrombolytic therapy or primary angioplasty has resulted in mortality reduction and the preservation of ventricular function in patients presenting with ST-elevation myocardial infarction (STEMI).123 Although it is clear that early reperfusion may lead to better survival in patients with STEMI, a significant number of patients arrive at the hospital beyond the window of opportunity (ie, 
12 h after symptom onset) for effective acute reperfusion therapy.4 Therefore, further improvements in the outcomes of AMI patients may be limited by delays in the patient’s arrival at the hospital or by delays in the reaction time of the treating hospitals (ie, door-to-lytic therapy time or door-to-balloon time).4567 In addition, the optimal management for STEMI patients who present to the hospital late in the course of their myocardial infarction remains uncertain.
While there have been randomized controlled trials89 supporting an early invasive approach to the treatment of patients with non-STEMI as late as 7 days after the inciting event, very few data have been reported1011 about the best course of action in STEMI patients who present to the hospital after experiencing > 12 h of symptoms. The scant evidence seems to suggest that late reperfusion with either thrombolytic agents or angioplasty may be of benefit. Approximately 2,400 patients enrolled in the Second International Study of Infarct Survival10 arrived between 13 and 24 h after chest pain onset, and reperfusion using a combination of aspirin and streptokinase resulted in a 33% reduction in vascular deaths. In the Medicine Versus Angiography in Thrombolytic Exclusion trial,11 those patients (60% of whom presented with a STEMI or its equivalent) who were randomized to receive early revascularization within a mean (± SD) duration of 9 ± 7 h from the onset of symptoms had a reduction in the incidence of recurrent ischemia or in-hospital death. Moreover, a prospective Swedish AMI registry12 containing > 10,000 patients with STEMI or its equivalent also showed that revascularization within 14 days of the index event with or without prior thrombolytic therapy was associated with a 36% reduction in total mortality. Despite the favorable outcomes, these data correspond to the results of subgroup analyses of trials that were not designed to address the potential benefit of late reperfusion, thus, robust conclusions should not be drawn at the present time.
Yip and colleagues, in this issue of CHEST (see page 38), described their experience of cardiac catheterization and percutaneous coronary intervention (PCI) for the management of 377 consecutive AMI patients, mainly those experiencing a STEMI or its equivalent, who presented to the hospital outside the acute reperfusion window. More than half of the patients had clear indications for an invasive workup (ie, postinfarction angina or advanced heart failure) according to the current American College of Cardiology/American Heart Association guidelines,13 most of them (87% [unpublished data]) had developed Q waves by the time of their intervention, and 11.4% of them had previously undergone thrombolytic therapy. Despite a lower incidence of glycoprotein IIb-IIIa inhibitor use of only 14.6% of patients and stent deployment in only 61% of patients, procedural success (90.2%) was comparable to the current standards.1415 The authors concluded that their approach was safe with similar 30-day mortality rates and 6-month clinical restenosis rates as those of contemporary AMI trials,1516 and was associated with a low long-term mortality rate of 12.5% at 39 months.
It would be difficult to directly compare the mortality rates of these patients with those of other AMI studies without adequate risk adjustment.17 The lower number of patients in the present study with Thrombolysis in Myocardial Infarction classification of coronary flow of 1 in the infarct-related artery (IRA) when compared to the numbers of patients in other STEMI studies (54.4% vs 70 to 90%1518), suggests that some of these patients already have some degree of reperfusion through the IRA territory, which could in part explain the relatively low 30-day mortality rate found by the authors. In addition, the absence of a control group makes further judgment more difficult, as a substantial portion of these patients would have low short-term and long-term mortality rates even if they were to be managed medically, given the high average ejection fraction post-AMI, relatively younger age (61 ± 11.4 years), a small percentage of heart failure (23.3%), and the prevalent use of ß-blockers, aspirin, and angiotensin-converting enzyme inhibitors.17 Therefore, the true benefit or harm of their invasive approach is still unknown.
The article does, however, identify significant predictors of failed PCI in this setting, including the timing of the procedure ( 3 days vs 
4 days from presentation with AMI) and the presence of a high thrombus burden in the IRA. The caveat is that several of the predictors of 30-day mortality are similar to the predictors of lack of response to PCI, such as advanced heart failure, diabetes, and multivessel disease. Thus, it is likely that the patients undergoing cardiac catheterization earlier in their presentation are the ones with the highest risk, with consequent worse outcomes for PCI. This point could be further clarified if the details between the time of presentation to the hospital and the time of the catheterization are reported, and if the indications for PCI at 3 days are identified. Nonetheless, the available information may still be useful when planning for an elective invasive workup of this patient population as it suggests that the optimal timing of PCI after STEMI, when the true "early reperfusion" opportunity has passed, is 4 days after the index event, if there are no clinical reasons to proceed to catheterization sooner.
In the absence of a controlled, randomized study, little has been learned about when or whether one should proceed to catheterization and angioplasty in this setting. Currently, the more ubiquitous use of stenting and the use of adjunctive therapy, such as that with glycoprotein IIb-IIIa inhibitors and/or clopidogrel, have been proven to improve the short-term outcomes of AMI patients undergoing PCI.151619 The use of glycoprotein IIb-IIIa inhibitors is especially beneficial in diabetic and high-risk AMI patients who are undergoing PCI to reduce acute ischemic complications and to improve long-term clinical outcomes.2021 The early initiation of these therapies prior to undergoing catheterization in patients presenting outside the reperfusion window would likely improve the outcome of PCI.
Further trials are necessary to determine the optimal course of therapy in patients who present more than > 12 to 24 h after the onset of symptoms of STEMI. Until then, a routine invasive workup of these patients is not indicated, and the patients who are most likely to benefit from an early invasive approach include those with a noninvasive workup identifying regions of residual myocardial viability and ischemia, or the presence of high-risk features such as recurrent angina, diabetes, heart failure, or shock.13
References
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