JACC: CARDIOVASCULAR INTERVENTIONS © 2010 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
VOL. 3, NO. 9, 2010 ISSN 1936-8798/$36.00 DOI: 10.1016/j.jcin.2010.08.004
EDITORIAL COMMENT
Intracoronary Thrombus A Sticky Problem* Mauricio G. Cohen, MD Miami, Florida More than 3 decades have passed since the demonstration of the pivotal role of coronary thrombosis in the pathophysiologic mechanism of acute coronary syndromes. Since then, most therapeutic interventions have aimed at dissolving the clot overlying the culprit plaque by pharmacological or mechanical means (1). Although fibrinolytic therapy became the standard of care for ST-segment elevation myocardial infarction (STEMI) patients, in which a fibrin-rich thrombus is responsible for complete epicardial coronary occlusion, its use in non–ST-segment elevation acute coronary syndrome (NSTACS) has been associated with equivocal and, at times, adverse results. In such cases, when the thrombus is more labile, rich in platelets, and incompletely occlusive, potent antiplatelet agents such as thienopyridines and glycoprotein (GP) IIb/IIIa inhibitors are currently the cornerstone therapy (2). Concurrently, technological developments gave the necessary tools to cardiologists to manage high-risk patients with the most challenging lesions in the catheterization laboratory. Primary percutaneous coronary intervention (PCI) and early invasive management became the standard of care for STEMI and NSTACS, respectively, in tertiary care centers (3,4). See page 937
The NSTACS patients with high Thrombolysis In Myocardial Infarction (TIMI) risk scores are more likely to have intracoronary visible thrombus, impaired angiographic flow, and greater extent of coronary atherosclerosis. Observational data demonstrated a stepwise increase in the prevalence of visible angiographic thrombus with increasing TIMI risk scores (30% with TIMI score 0 to 2, 36% with TIMI score 3 to 4, and 41% with TIMI score 5 to 7, p ⬍ 0.001) (5). Coronary thrombus is a significant challenge in the cathe-
*Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology. From the Cardiovascular Division, University of Miami Miller School of Medicine, Miami, Florida. Dr. Cohen receives research support from Regado Biosciences, Inc. and Invitrox, Inc., consulting honoraria from Regado Biosciences, Inc., Medtronic, Inc., Momenta Pharmaceuticals, and Terumo Medical, and is a member of the Speakers’ Bureau for Medtronic, Inc. and Terumo Medical.
terization laboratory and is identified as a filling defect surrounded by contrast or staining at the site of a high-grade lesion or total occlusion or upward convexity or irregularity without vessel tapering at the site of an abrupt occlusion. Early angiographic studies revealed that the presence of visible thrombus was the strongest predictor of poor clinical outcomes, such as death, myocardial infarction, and need for urgent revascularization after PCI (6). These increased adverse event rates are likely a consequence of distal embolization and no-reflow, which correlate with higher incidence of left ventricular systolic dysfunction, malignant ventricular arrhythmias, heart failure, and cardiac rupture. Macro- or microembolization in a coronary territory can cause capillary damage, endothelial swelling, myocyte edema, and neutrophil infiltration resulting in inadequate myocardial perfusion without epicardial vessel obstruction (7,8). In this issue of JACC: Cardiovascular Interventions, Srinivasan et al. (9) report the outcomes of 6,227 patients undergoing PCI in native vessels with thrombus-containing lesions at a single high-volume center. Data were broken down according to 3 periods in interventional cardiology: an early stent era with Palmaz-Schatz and Gianturco-Roubin stents (January 1990 to December 1996), a bare-metal stent (BMS) era with more flexible and deliverable metal stents and routine use of intravenous and oral antiplatelet agents (January 1997 to March 2003), and a period intended to represent current practice with a rapid and sustained uptake in drug-eluting stent (DES) use, mostly for “off-label” indications (April 2003 to August 2006). An important caveat is that after the presentation of controversial data about long-term safety of DES at the European Congress of Cardiology in September 2006, DES use dropped sharply in the U.S. (10). Furthermore, the data presented in this study precede the U.S. Food and Drug Administration advisory panel meeting on DES safety and the recommendations issued by professional associations regarding the risks of dual antiplatelet therapy discontinuation within 12 months of stent implantation (11). A previous publication of the Mayo Clinic experience with PCI in thrombotic lesions showed improved procedural success but no differences in major adverse cardiac events (MACE) among patients treated during the early and late BMS eras (before and after 1996) (12). The current report confirms previous findings and extends the results to DES-treated patients. Procedural success improved from 43%, in the early stent era, to 85% to 86% in the BMS and DES eras, despite the increasing prevalence of more complex and flow-limiting lesions. Explanations include the steep increase in use of GP IIb/IIIa inhibitors from 8% to approximately 80% and stents from ⬍10% to more than 90% that occurred after 1996, with a modest uptake of mechanical thrombectomy devices of 5% to 6%, mostly at the expense of rheolytic devices and ⬍1% use of manual aspiration catheters. Although the authors should be commended for their thor-
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Cohen Editorial Comment
ough analysis, these data represent the practice pattern in a single institution up to calendar year 2006, and they might not necessarily reflect more recent trends. The adjunctive use of GP IIb/IIIa inhibitors during primary PCI is associated with a significant reduction in death and reinfarction rates (13). In NSTACS, upstream use of GP IIb/IIIa inhibitors reduces thrombus burden and improves coronary flow (14). However, after the recognition of bleeding in the early 2000s, as a determinant of major adverse outcomes, the use of GP2b3a inhibitors dropped substantially in the U.S. (15). During the same period, clinical trials demonstrated that bivalirudin provides stable anticoagulation during PCI with less bleeding than heparin and GP IIb/IIIa inhibitors (16). Furthermore, the unexpected reduction in 30-day cardiac mortality seen with bivalirudin in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial was almost exclusively driven by a reduction in major bleeding, despite a greater occurrence of acute stent thrombosis (17). Of note, bivalirudin was not used in the Mayo Clinic experience. Manual thrombectomy aspiration catheters have become a popular tool in the management of thrombotic lesions and as an adjunct to primary PCI, mainly because of simplicity, ease of use, and randomized data supporting these catheters. A recent meta-analysis showed significant improvement in final TIMI flow, higher myocardial blush grade, less distal embolization, and lower mortality with use of manual aspiration thrombectomy (18). The TAPAS (Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study), with the largest sample size (n ⫽ 1,071), showed decreased 1-year mortality and was published in 2008 —2 years after the end of the DES period of the Mayo Clinic report, possibly explaining the low use of aspiration thrombectomy (19). Interestingly, rheolytic thrombectomy was the preferred strategy in the Mayo Clinic during the studied time period. The Angiojet device was approved in the late 1990s and at the time was considered an effective tool for intracoronary thrombus management. However, this technique lost its appeal and became a niche device after the publication of the AIMI (AngioJet Rheolytic Thrombectomy In Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction) trial, which showed no differences in infarct size or STsegment resolution and increased mortality with rheolytic thrombectomy (20). The Mayo Clinic report provides reassurance regarding the use of stents, either BMS or DES, in thrombuscontaining lesions, and this is a major contribution of the study. Major adverse cardiac events were significantly reduced in the BMS and DES eras in comparison with the early stent era. Interestingly, the survival—free of MACE and target lesion revascularization— curves at 4 years showed an intriguing difference in shape between patients
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treated in the DES and BMS eras. Initial outcomes seemed to be improved during the DES era, with a late attrition after 2 years. Unfortunately, the current study cannot answer whether this finding was a consequence of late stent thrombosis, but it remains a possibility, considering that patients were treated before the introduction of prolonged dual antiplatelet therapy (9). Interventional cardiology is constantly evolving, with rapidly changing practices. Future studies will hopefully determine the effect of widespread use of manual aspiration thrombectomy and the optimal antithrombotic strategy for the management of challenging thrombotic lesions. At least we know that stents seem to be safe in this setting, but the thrombus issue will continue to stick for the time being. Acknowledgments
The author would like to acknowledge the critical review by Dr. Mauro Moscucci and the editorial assistance by Mr. Eric Scot Shaw. Reprint requests and correspondence: Dr. Mauricio G. Cohen, Cardiovascular Division, University of Miami Miller School of Medicine, 1400 Northwest 12th Avenue, Suite 1179, Miami, Florida 33136. E-mail:
[email protected].
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10. Gualano SK, Gurm HS, Share D, et al. Temporal trends in the use of drug-eluting stents for approved and off-label indications: a longitudinal analysis of a large multicenter percutaneous coronary intervention registry. Clin Cardiol 2010;33:111– 6. 11. Grines CL, Bonow RO, Casey DE Jr., et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol 2007;49:734 –9. 12. Singh M, Berger PB, Ting HH, et al. Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience). Am J Cardiol 2001;88:1091– 6. 13. De Luca G, Suryapranata H, Stone GW, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA 2005;293: 1759 – 65. 14. Zhao XQ, Theroux P, Snapinn SM, Sax FL, PRISM-PLUS Investigators. Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non–Q-wave myocardial infarction. Angiographic results from the PRISM-PLUS trial (Platelet receptor inhibition for ischemic syndrome management in patients limited by unstable signs and symptoms). Circulation 1999;100:1609 –15.
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15. Roe MT, Messenger JC, Weintraub WS, et al. Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol 2010;56:254 – 63. 16. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355:2203–16. 17. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008;358: 2218 –30. 18. De Luca G, Dudek D, Sardella G, Marino P, Chevalier B, Zijlstra F. Adjunctive manual thrombectomy improves myocardial perfusion and mortality in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized trials. Eur Heart J 2008;29:3002–10. 19. Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet 2008;371:1915–20. 20. Ali A, Cox D, Dib N, et al. Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study. J Am Coll Cardiol 2006;48:244 –52.
Key Words: acute coronary syndromes aspiration thrombectomy coronary thrombosis.
