Management of Thrombotic Lesions

Introduction

Acute myocardial infarction is caused by thrombotic occlusion of a native coronary artery. While partial occlusion usually presents as a non ST-elevation myocardial infarction (NSTEMI), it is expected that complete occlusion will result in ST-elevation myocardial infarction (STEMI). Acute myocardial infarction can also occur as a result of thrombotic occlusion of a saphenous vein graft. Saphenous vein graft occlusion may be associated with larger thrombus burden than native coronary artery occlusion and therefore may require different strategies for management. Stent thrombosis is becoming increasingly recognized as a distinct cause of acute myocardial infarction.

Primary percutaneous coronary intervention (PCI) is effective at reperfusing or recanalizing the infarct related artery with a success rate that exceeds 90%. Traditionally this has been accomplished by passing an uninflated coronary balloon “back and forth” across the thrombus, possibly coupled with serial balloon inflations at the site of occlusion. This established the term “door-to-balloon time” that is currently used as a quality metric for catheterization laboratories that offer primary PCI. Unfortunately, such disruption of thrombus likely results in macro- and micro-embolization into the downstream coronary bed. Impaired myocardial perfusion can be observed by failure of electrocardiographic ST-segments to return to baseline. This can also be observed during coronary angiography by assessment of myocardial blush grade, which represents flow in the micro-circulation (0 = no blush, 1 = minimal blush, 2 = moderate blush, and 3 = normal blush). Despite successful epicardial coronary flow, impaired myocardial flow (blush grade 0 to 2) has been observed in over 70% of patients. Impaired myocardial perfusion has been associated with poor prognosis. For example, after coronary flow is re-established in acute myocardial infarction, no ST-segment resolution is associated with 29% long-term mortality compared with 4% for complete resolution. Similarly, poor myocardial blush (grade 0/1) is associated with 23% long-term mortality compared with 3% for normal blush (grade 3).

Accordingly, different strategies have been developed to manage thrombus during primary PCI in order to mitigate the adverse effects associated with embolization. This review will principally center on the current pharmacological and mechanical approaches to manage thrombotic lesions.

Stent Thrombosis

An important etiology of acute myocardial infarction is stent thrombosis. In fact, in a relatively large registry, the proportion of STEMI cases due to stent thrombosis increased from 6% in 2003 to 2004, to approximately 11% in 2009 to 2010. This is important since primary PCI for stent thrombosis is less effective (76% to 80% successful reperfusion) than primary PCI for native artery occlusion. STEMI due to stent thrombosis is also associated with an increased risk for long-term myocardial infarction (~23%) and repeat stent thrombosis (~15%) compared with STEMI due to native artery occlusion.

With current generation drug-eluting stents (everolimus and zotarolimus-eluting), late and very late stent thrombosis is exceedingly rare; however, this complication is still seen during periods of inadequate antiplatelet therapy. Inadequate antiplatelet therapy might be the result of poor patient compliance, but is also seen among patients undergoing noncardiac surgical procedures who have been instructed to minimize or stop their antiplatelet therapy.

Pharmacological Strategies to Improve Myocardial Perfusion

Facilitated PCI has been studied as a potential mechanism to improve outcomes during acute myocardial infarction. With this approach it was hoped that improvement in preprocedure coronary flow could reduce infarct size and improve survival. PCI can be facilitated by potent antiplatelet agents (i.e., glycoprotein IIb/IIIa inhibitors) or by thrombolytic agents. Dong et al. performed a metaanalysis on nearly 3000 STEMI patients who received upstream eptifibatide or tirofiban versus in-lab eptifibatide or tirofiban. Although upstream glycoprotein inhibitor use was associated with improved preprocedure coronary flow, it did not reduce recurrent myocardial infarction or mortality. Glycoprotein IIb/IIIa inhibitors can also be administered intra-coronary, rather than intravenous; however, recent randomized trial data did not find a benefit in regard to survival or recurrent myocardial infarction from this approach.

The Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial randomized nearly 2500 patients who presented within 6 hours of a STEMI to one of the following study drug strategies: upstream abciximab versus upstream abciximab with half-dose reteplase versus upstream placebo. Efficacy was similar between all treatment arms; however, major bleeding was increased from a facilitated approach, especially with thrombolytic therapy. Major bleeding was 10.1% with upstream abciximab versus 14.5% with upstream abciximab with half-dose reteplase versus 6.9% with upstream placebo. Eitel et al. also conducted a metaanalysis to examine the association between facilitated PCI and mortality. Compared with primary PCI, the odds ratio (OR) for mortality from glycoprotein IIb/IIIa inhibitor–facilitated PCI was 0.88, 95% confidence interval (CI), 0.59 to 1.33; for thrombolytic-facilitated PCI, OR = 1.47; 95% CI, 0.96 to 2.25; and for combination glycoprotein IIb/IIIa inhibitor/half-dose thrombolytic–facilitated PCI, OR = 1.22; 95% CI, 0.55 to 2.67. Therefore, facilitated PCI does not appear to improve survival and, in the case of thrombolytics, may even be associated with harm.

Mechanical Strategies to Improve Myocardial Perfusion