European Heart Journal Advance Access originally published online on February 13, 2007
European Heart Journal 2007 28(5):531-532; doi:10.1093/eurheartj/ehl514
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Ruminating on OAT: is the case closed?
2-51 Medical Sciences Building, University of Alberta Edmonton, Alberta, T6G 2H7 Canada
Received 14 November 2006; revised 9 January 2007; accepted 12 January 2007; online publish-ahead-of-print 13 February 2007.
* Corresponding author. Tel: +1 780 492 0591; fax: +1 780 492 9486. E-mail address: paul.armstrong{at}ualberta.ca
Occlusion of an epicardial coronary artery is a well recognized pathophysiological substrate for acute ST-elevation myocardial infarction (MI). Whether and how coronary patency is restored after this event is markedly variable among patients. Unquestionably, coronary reperfusion enhances clinical outcomes and can occur spontaneously or through pharmacological or mechanical methods.1 Moreover, if the culprit coronary artery associated with MI is open prior to an attempt at mechanical coronary intervention, a better long-term clinical outcome results.2
Since the long-term outlook for patients recovering from MI appears enhanced when the culprit coronary artery is patent, enthusiasm for opening occluded arteries—even at a time point substantially removed from the acute event—has emerged as an increasingly common feature of clinical practice.3 Somewhat remarkably, this has developed despite the paucity of robust scientific data to support it as reflected by a Class 2b recommendation in the ACC/AHA percutaneous coronary intervention (PCI) guidelines.4 In contrast, the 2005 European PCI guidelines opine that ‘there is no agreement on treatment recommendations for this group of patients’ and indicate they will need to await the results of the Occluded Artery Trial (OAT) trial.5,6
Proponents have also argued that the acute inflammatory process, structural remodelling, and apoptosis contributing to healing and functional restoration of the left ventricle after infarction may be favourably modulated by achieving coronary patency beyond the traditional 12 h window from symptom onset when salvage of myocardial tissue is unlikely. In addition to promoting left ventricular healing, arguments supporting late opening of occluded culprit coronary arteries include restoration of electrical stability, restraining left ventricular dilatation and supplying myocardial territories distant from the culprit vessel through intercoronary collateral flow.3
Recently, the OAT investigators address this issue in over 2000 high-risk stable patients with total infarct related coronary occlusion 3–28 days post MI.7 In this open label randomized trial of PCI, usually employing bare metal stenting, a high rate of initial procedural success with good 1 year patency (among a subset) was achieved. Despite successful mechanical intervention, the expected decline in death, MI, and heart failure did not occur. In fact, the reverse tended to be true. Hence there was a statistically greater incidence of fatal and non-fatal MI in the intervention vs. medical group as ascertained by investigators (after central adjudication the overall frequency of events fell but a similar trend persisted).
Hence, the OAT trial not only demonstrates no benefit but also the potential for harm when mechanical coronary intervention in an occluded coronary artery is undertaken in stable patients at a median of 8 days after MI. Notwithstanding this, PCI remains a key primary therapy for ST-elevation MI as well playing an important role in those patients requiring rescue after failed fibrinolysis or who have easily provokable or spontaneous recurrent ischaemia during MI convalescene.1,8,9
What could account for the apparent negative impact of PCI in patients with occluded coronary arteries? Peri-procedural MI associated with branch occlusion and distal embolization either into the culprit vessel or a differing vascular territory, remain open possibilities. It could be argued that the definition of anatomic success after PCI was too liberal in OAT given it included patients with less than TIMI 3 epicardial flow and even those with grade 1 antegrade flow perceived to be exclusively related to suboptimal microvascular coronary flow. In the companion angiographic substudy of OAT, although 1 year patency rates for PCI were 83 vs. 25% for medical therapy P < 0.0001, there was an equivalent improvement in ejection fraction.10 It is worth emphasizing that the median time from symptom onset to randomization was 8 days with a wide entry window of 3 to 28 days. Since much of the healing and remodelling after infarction occurs within the first week, a quicker ascertainment and intervention might well have yielded a different result as has been the case with angiotensin inhibitors.11 When OAT was originally designed, it was anticipated that the medical group would experience a 3 year event rate of 25 vs. the 15.6% over 4 years reported. This better outcome with medical therapy is likely attributable in part at least to the high use of aspirin beta-blockers, angiotensin antagonists, and lipid lowering agents.7 Moreover, since OAT commenced there have been further advances in both the content of medical therapy as well as system quality measures that enhance compliance with evidence-based regimens. Thus, it is conceivable that the outlook for the medically treated patients in OAT would be even better in 2007 where greater usage of clopidogrel and aldosterone antagonism would be the norm. Although some would argue that greater use of drug eluting stents might have yielded better results in the intervention arm of OAT, this seems unlikely given recent data suggesting the contrary.12 Finally, there may be yet more to be learned about the patients enrolled in OAT. One of five patients received fibrinolysis and it is impossible to know from current study whether persisting occlusion vs. reperfusion followed by reocclusion may have occurred. This issue along with the question of whether persisting myocardial viability would signal the potential for benefit vs. harm with late mechanical intervention deserves further exploration.
The OAT investigators are to be commended for having conducted a novel, definitive, and landmark study which gives us closure on one key element of the open artery hypothesis. Hence, solid grounds now exist to alter the practice of those prematurely committed to mechanical intervention of occluded culprit coronary arteries in high-risk stable patients recovering from acute MI. Since the patient population represented in OAT is likely to further expand in the future, enthusiasm for earlier co-intervention and the evaluation of alternative molecular and cell-based methods for revascularization should likely emerge.13,14
Conflict of interest: none declared.
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The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
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