Predictors of coronary stent thrombosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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## Contents

* 1 Overview
* 2 Risk factors for early and late stent thrombosis
* 3 Risk factors for very late stent thrombosis
* 4 References

## Overview

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A number of clinical, angiographic, and procedural factors predispose to the occurrence of stent thrombosis. Predictors of stent thrombosis can be classified into anatomic variables, procedure related variables and clinical variables. A new entity which has been recently recognised and is being increasingly studied in relation to stent thrombosis is hyporesponsiveness to antiplatelet agents.

Procedure related variables: Procedure related variables include stent underexpansion, margin dissections, incomplete wall apposition, residual inflow and outflow disease, overlapping stent, polymer materials and use of self expanding or coil stents[1].

Anatomic variables: Lesion-specific factors that increase the likelihood of stent thrombosis include a residual dissection at the margin of the stent, impaired flow into or out of the stent, small stent diameters (<3 mm), long stent lengths, and treatment of an acute myocardial infarction[1].

Clinical variables: Clinical variables include acute myocardial infarction, clopidogrel noncompliance and discontinuation, hyporesponsiveness to antiplatelet agents, higher baseline platelet count, diabetes mellitus, renal failure, congestive heart failure, prior radiation brachytherapy[1][2].

In addition to these, stent implantation for off-label indication of both DES and BMS(such as restenotic lesions, bypass graft lesions, left main coronary artery disease, as well as ostial, bifurcated, and totally occluded lesions) has been associated with higher rates of ischemic complications, including stent thrombosis, as compared with standard indications[3][4]. In a case control study of 145 patients with stent thrombosis by Rinaldi et al[1], presence of angiographic thrombus prior to stenting, greater total stent length, higher baseline platelet count, acute MI indication, the use of a self expanding or coil stent, and GpIIb-IIIa exposure were identified as the strongest predictors of stent thrombosis.

In another study by Marroquin et al[5] to compare the outcomes in bare-metal versus drug-elting stents for off-label indications showed that one year after intervention, there were no significant differences in the adjusted risk of death or myocardial infarction in patients with drug eluting stents as compared with those with bare metal stents. These findings implicate that the poorer outcome observed after stenting for off-label indications are related to patient and lesion characteristics but not to the stent itself. Therefore, large randomized clinical trial are needed to further study the use of DES for off label versus standard indications.

## Risk factors for early and late stent thrombosis

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1. Premature discontinuation of antiplatelets/clopidogrel[6][2][7]
2. Abscence/dysfunction of CYP2C19 allele which is required for the conversion of clopidogrel to its active metabolite.[8]
3. Improper opposition of the stent or undersized stent[6][9]
4. Length of the stent- greater the length, higher the risk[10]
5. Malignancy[6]
6. Cocaine use[11][12]
7. Small caliber of the vessels[10]
8. Slow intra coronary flow post PCI[13]
9. Bifurcation lesion[2]
10. Inadequate periprocedural anticoagulation[14]
11. Low ejection fraction (<30%)[13][2][6]
12. Nonionic contrast media[15]
13. Prior brachytherapy
14. Small stent area on intracoronary ultrasound[16]
15. Residual plaque/thrombus/dissection after stent placement[17][13][10]
16. CAD ≥50% proximal of culprit lesion[6]
17. Chronic kidney disease[2][18]
18. Diabetes mellitus[19][2]
19. Black race[20]
20. Elevated C-reactive protein levels[21]
21. Hypersensitivity to stents[22]
22. Young age[19]
23. Paclitaxel-eluting stent implantation[19]
24. Multivessel disease[23]
25. Acute coronary syndrome at presentation[24]

## Risk factors for very late stent thrombosis

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1. Ongoing vessel inflammation[25]
2. Delayed neointimal coverage which is usually seen with DES when compared to BMS[26][25]

## References

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1. ↑ 1.0 1.1 1.2 1.3 Rinaldi MJ, Kirtane AJ, Piana RN; et al. (2008). "Clinical, procedural, and pharmacologic correlates of acute and subacute stent thrombosis: results of a multicenter case-control study with 145 thrombosis events". Am. Heart J. 155 (4): 654–60. doi:10.1016/j.ahj.2007.11.028. PMID 18371472. Unknown parameter `|month=` ignored (help)CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Iakovou I, Schmidt T, Bonizzoni E; et al. (2005). "Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents". JAMA. 293 (17): 2126–30. doi:10.1001/jama.293.17.2126. PMID 15870416. Unknown parameter `|month=` ignored (help)CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
3. ↑ Beohar N, Davidson CJ, Kip KE; et al. (2007). "Outcomes and complications associated with off-label and untested use of drug-eluting stents". JAMA. 297 (18): 1992–2000. doi:10.1001/jama.297.18.1992. PMID 17488964. Unknown parameter `|month=` ignored (help)CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
4. ↑ Win HK, Caldera AE, Maresh K; et al. (2007). "Clinical outcomes and stent thrombosis following off-label use of drug-eluting stents". JAMA. 297 (18): 2001–9. doi:10.1001/jama.297.18.2001. PMID 17488965. Unknown parameter `|month=` ignored (help)CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
5. ↑ Marroquin OC, Selzer F, Mulukutla SR; et al. (2008). "A comparison of bare-metal and drug-eluting stents for off-label indications". N. Engl. J. Med. 358 (4): 342–52. doi:10.1056/NEJMoa0706258. PMC 2761092. PMID 18216354. Unknown parameter `|month=` ignored (help)CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
6. ↑ 6.0 6.1 6.2 6.3 6.4 van Werkum JW, Heestermans AA, Zomer AC, Kelder JC, Suttorp MJ, Rensing BJ; et al. (2009). "Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry". J Am Coll Cardiol. 53 (16): 1399–409. doi:10.1016/j.jacc.2008.12.055. PMID 19371823.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
7. ↑ Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS; et al. (2006). "Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry". Circulation. 113 (24): 2803–9. doi:10.1161/CIRCULATIONAHA.106.618066. PMID 16769908.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
8. ↑ Gladding P, Webster M, Zeng I, Farrell H, Stewart J, Ruygrok P; et al. (2008). "The pharmacogenetics and pharmacodynamics of clopidogrel response: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial". JACC Cardiovasc Interv. 1 (6): 620–7. doi:10.1016/j.jcin.2008.09.008. PMID 19463375.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
9. ↑ Colombo A, Hall P, Nakamura S, Almagor Y, Maiello L, Martini G; et al. (1995). "Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance". Circulation. 91 (6): 1676–88. PMID 7882474.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
10. ↑ 10.0 10.1 10.2 Cutlip DE, Baim DS, Ho KK, Popma JJ, Lansky AJ, Cohen DJ; et al. (2001). "Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials". Circulation. 103 (15): 1967–71. PMID 11306525.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
11. ↑ Lemos PA (2007). "Hidden drugs, hidden risks--is cocaine use a new risk factor for stent thrombosis?". Catheter Cardiovasc Interv. 69 (7): 959–60. doi:10.1002/ccd.21239. PMID 17525956.
12. ↑ McKee SA, Applegate RJ, Hoyle JR, Sacrinty MT, Kutcher MA, Sane DC (2007). "Cocaine use is associated with an increased risk of stent thrombosis after percutaneous coronary intervention". Am Heart J. 154 (1): 159–64. doi:10.1016/j.ahj.2007.04.004. PMID 17584570.CS1 maint: Multiple names: authors list (link)
13. ↑ 13.0 13.1 13.2 Moussa I, Di Mario C, Reimers B, Akiyama T, Tobis J, Colombo A (1997). "Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome". J Am Coll Cardiol. 29 (1): 6–12. PMID 8996288.CS1 maint: Multiple names: authors list (link)
14. ↑ Grines CL, Bonow RO, Casey DE, Gardner TJ, Lockhart PB, Moliterno DJ; et al. (2007). "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". Circulation. 115 (6): 813–8. doi:10.1161/CIRCULATIONAHA.106.180944. PMID 17224480.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
15. ↑ Scheller B, Hennen B, Pohl A, Schieffer H, Markwirth T (2001). "Acute and subacute stent occlusion; risk-reduction by ionic contrast media". Eur Heart J. 22 (5): 385–91. doi:10.1053/euhj.2000.2319. PMID 11207080.CS1 maint: Multiple names: authors list (link)
16. ↑ Nakamura S, Colombo A, Gaglione A, Almagor Y, Goldberg SL, Maiello L; et al. (1994). "Intracoronary ultrasound observations during stent implantation". Circulation. 89 (5): 2026–34. PMID 8181126.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
17. ↑ Cheneau E, Leborgne L, Mintz GS, Kotani J, Pichard AD, Satler LF; et al. (2003). "Predictors of subacute stent thrombosis: results of a systematic intravascular ultrasound study". Circulation. 108 (1): 43–7. doi:10.1161/01.CIR.0000078636.71728.40. PMID 12821553.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
18. ↑ Kuchulakanti PK, Chu WW, Torguson R, Ohlmann P, Rha SW, Clavijo LC; et al. (2006). "Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus- and paclitaxel-eluting stents". Circulation. 113 (8): 1108–13. doi:10.1161/CIRCULATIONAHA.105.600155. PMID 16490815.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
19. ↑ 19.0 19.1 19.2 Wenaweser P, Daemen J, Zwahlen M, van Domburg R, Jüni P, Vaina S; et al. (2008). "Incidence and correlates of drug-eluting stent thrombosis in routine clinical practice. 4-year results from a large 2-institutional cohort study". J Am Coll Cardiol. 52 (14): 1134–40. doi:10.1016/j.jacc.2008.07.006. PMID 18804739.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
20. ↑ Collins SD, Torguson R, Gaglia MA, Lemesle G, Syed AI, Ben-Dor I; et al. (2010). "Does black ethnicity influence the development of stent thrombosis in the drug-eluting stent era?". Circulation. 122 (11): 1085–90. doi:10.1161/CIRCULATIONAHA.109.907998. PMID 20805432.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
21. ↑ Park DW, Yun SC, Lee JY, Kim WJ, Kang SJ, Lee SW; et al. (2009). "C-reactive protein and the risk of stent thrombosis and cardiovascular events after drug-eluting stent implantation". Circulation. 120 (20): 1987–95. doi:10.1161/CIRCULATIONAHA.109.876763. PMID 19884467.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
22. ↑ Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J; et al. (2006). "Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project". J Am Coll Cardiol. 47 (1): 175–81. doi:10.1016/j.jacc.2005.07.071. PMID 16386683.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
23. ↑ Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ; et al. (2009). "Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease". N Engl J Med. 360 (10): 961–72. doi:10.1056/NEJMoa0804626. PMID 19228612.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)  Review in: Ann Intern Med. 2009 Jul 21;151(2):JC1-8, JC1-9
24. ↑ Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C; et al. (2007). "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. 369 (9562): 667–78. doi:10.1016/S0140-6736(07)60314-6. PMID 17321312.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
25. ↑ 25.0 25.1 Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E; et al. (2006). "Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk". J Am Coll Cardiol. 48 (1): 193–202. doi:10.1016/j.jacc.2006.03.042. PMID 16814667.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
26. ↑ Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC; et al. (2007). "Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization". Circulation. 115 (18): 2435–41. doi:10.1161/CIRCULATIONAHA.107.693739. PMID 17438147.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)