Donald E. Cutlip MD
　　Executive Director， Clinical Investigations， Harvard Clinical Research Institute(HCRI).  Faculty， Beth Israel Deaconess Medical Center

　　Stent thrombosis remains a catastrophic complication of percutaneous coronary intervention.  The timing or risk period for stent thrombosis has been recognized as an important consideration after stenting for either stable coronary artery disease or acute coronary syndrome.  The Academic Research Consortium classification identifies events as early (0-30 days)， late (31 -365 days) and very late (>1 year).(1)  The clinical manifestations and predictors at various time periods are better described as a continuum rather than by discrete intervals， although the events beyond 1 year are more different than early or late events.  Thus for presentation purposes， we find it useful to combine early and late stent thrombosis as contrasted with very late stent thrombosis.  While much attention has been placed on the risk for very late stent thrombosis since the recognition in late 2006 of a slight but important increased risk for drug-eluting stents (DES) versus bare-metal stents (BMS)， the early period remains the highest risk for both device types.  In general， the prevalence of early and late stent thrombosis has been similar for a variety of BMS and DES.  In simple lesions this risk is approximately 1%， (2-4) while it is much higher in more complex lesions， with risk increased significantly for longer lesions， bifurcations and multi-vessel procedures.(5，6)  Other procedural factors such as stent underexpansion and residual dissection and patient factors such as diabetes and renal failure are associated with increased risk for early and late stent thrombosis.  While these factors explain most of the risk in the early and late period among patients who remain compliant with dual anti-platelet therapy (DAPT)， the early discontinuation of DAPT is a powerful risk factor， with a hazard ratio of 25-50 if discontinued in the first 3-6 months and even more so if in the first 30 days.  The risk period is probably longer for DES versus BMS and has led to guidelines advising a minimum of 12 months of DAPT after DES.
　　Although the prevalence and risk factors for early and late stent thrombosis are fairly well defined， the risk factors for very late stent thrombosis have been less clear.  Very late stent thrombosis has been evident out to at least 5-6 years and does occur with both BMS and DES.  Some studies suggest the risk is higher with DES， although this has not been confirmed in an adequately powered and controlled clinical study.  Pathologic data show delayed healing and ongoing inflammatory changes that are greater for DES and especially evident in cases of very late stent thrombosis.(7)  In clinical trial populations the risk is approximately 0.2% per year.(8)  The processes leading to delayed healing may be greater in more complex lesions as suggested by higher rates of very late stent thrombosis in these populations compared with clinical trial populations.  In one large registry of routine clinical practice the risk was 0.6% per year. (9)  Clinical and pathologic data suggest that additional risk factors may include bifurcation stenting and stenting of lipid rich plaque.
　　Most data are available in stable coronary artery disease or mixed populations， but it appears that acute coronary syndrome and ST elevation MI (STEMI) in particular are risk factors for early， late and very late stent thrombosis.  As in stable disease， the highest risk period is early with event rates of 3-5% at 1 year after STEMI.(10，11)  Randomized clinical trials have not shown a difference between BMS and DES， but a recent registry landmark analysis suggested the rate beyond 1 year was higher for DES， continuing at 1.9% per year for DES versus 0.6% per year for BMS.(11)
　　Stent thrombosis at all time intervals and in both stable coronary artery disease and acute coronary syndromes remains an important concern.  Issues for continued study include the optimal duration of DAPT， personalized DAPT based on platelet activation and clinical indication for stent， case selection for BMS versus DES based on relative risk for restenosis and stent thrombosis versus bleeding and compliance with DAPT， and improvements in stent technology to lower both the risk for early as well as later events.
　　1.Cutlip DE， Windecker S， Mehran R， Boam A， Cohen DJ， van Es GA， Steg PG， Morel MA， Mauri L， Vranckx P and others. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115(17):2344-51.
　　2.Cutlip DE， Baim DS， Ho KK， Popma JJ， Lansky AJ， Cohen DJ， Carrozza JP， Jr.， Chauhan MS， Rodriguez O， Kuntz RE. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation 2001;103(15):1967-71.
　　3.Moses JW， Leon MB， Popma JJ， Fitzgerald PJ， Holmes DR， O’Shaughnessy C， Caputo RP， Kereiakes DJ， Williams DO， Teirstein PS and others. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349(14):1315-23.
　　4.Stone GW， Ellis SG， Cox DA， Hermiller J， O’Shaughnessy C， Mann JT， Turco M， Caputo R， Bergin P， Greenberg J and others. One-year clinical results with the slow-release， polymer-based， paclitaxel-eluting TAXUS stent: the TAXUS-IV trial. Circulation 2004;109(16):1942-7.
　　5.Serruys PW， Unger F， Sousa JE， Jatene A， Bonnier HJ， Schonberger JP， Buller N， Bonser R， van den Brand MJ， van Herwerden LA and others. Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med 2001;344(15):1117-24.
　　6.Iakovou I， Schmidt T， Bonizzoni E， Ge L， Sangiorgi GM， Stankovic G， Airoldi F， Chieffo A， Montorfano M， Carlino M and others. Incidence， predictors， and outcome of thrombosis after successful implantation of drug-eluting stents. Jama 2005;293(17):2126-30.
　　7.Finn AV， Joner M， Nakazawa G， Kolodgie F， Newell J， John MC， Gold HK， Virmani R. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 2007;115(18):2435-41.
　　8.Mauri L， Hsieh WH， Massaro JM， Ho KK， D’Agostino R， Cutlip DE. Stent Thrombosis in Randomized Clinical Trials of Drug-Eluting Stents. N Engl J Med 2007;356:1020-9.
　　9.Daemen J， Wenaweser P， Tsuchida K， Vaina S， Abrecht L， Morger C， Kukreja N， Jüni P， Sianos G， Hellige G and others. Early and Late Coronary Stent Thrombosis of Sirolimus-Eluting and Paclitaxel-Eluting Stents in Routine Clinical Practice: Data from a Large Two-Institutional Cohort Study. Lancet 2007;369:667-678.
　　10.Stone GW， Lansky AJ， Pocock SJ， Gersh BJ， Dangas G， Wong SC， Witzenbichler B， Guagliumi G， Peruga JZ， Brodie BR and others. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med 2009;360(19):1946-59.
　　11.Brodie B， Pokharel Y， Fleishman N， Bensimhon A， Kissling G， Hansen C， Milks S， Cooper M， McAlhany C， Stuckey T. Very late stent thrombosis after primary percutaneous coronary intervention with bare-metal and drug-eluting stents for ST-segment elevation myocardial infarction: a 15-year single-center experience. JACC Cardiovasc Interv 2011;4(1):30-8.