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Table of Contents
Year : 2011  |  Volume : 12  |  Issue : 1  |  Page : 22-25  

Very late stent thrombosis of Sirolimus-eluting stent 59 months after implantation: A first report from the Middle-East and review of literature

Department of Cardiology, Royal Hospital, Muscat, Oman

Date of Web Publication25-May-2011

Correspondence Address:
Prashanth Panduranga
Department of Cardiology, Royal Hospital, Post Box 1331, Muscat 111
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1995-705X.81557

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Very late stent thrombosis occurs more frequently with drug-eluting stents and tends to occur despite dual antiplatelet therapy or after long periods of clopidogrel discontinuation. Stent thrombosis commonly presents with myocardial infarction or death. We report a 41-year-old Arab male with very late stent thrombosis after 59 months of sirolimus-eluting stent implantation and -49 months after clopidogrel discontinuation despite aspirin continuation, presenting with exertional angina. He underwent successful percutaneous coronary intervention. This case underlines the need for novel stent designs as well as newer therapeutic strategies in preventing very late stent thrombosis among patients receiving drug-eluting stents.

Keywords: Drug-eluting stent, sirolimus-eluting stent, stent thrombosis, very late stent thrombosis

How to cite this article:
Panduranga P, Al-Mukhaini M. Very late stent thrombosis of Sirolimus-eluting stent 59 months after implantation: A first report from the Middle-East and review of literature. Heart Views 2011;12:22-5

How to cite this URL:
Panduranga P, Al-Mukhaini M. Very late stent thrombosis of Sirolimus-eluting stent 59 months after implantation: A first report from the Middle-East and review of literature. Heart Views [serial online] 2011 [cited 2023 Dec 8];12:22-5. Available from: https://www.heartviews.org/text.asp?2011/12/1/22/81557

   Introduction Top

Coronary artery stents, particularly drug-eluting stents (DES), are used in the majority of patients who undergo percutaneous coronary intervention (PCI). Stent thrombosis is an uncommon but serious complication of coronary artery stents that almost always presents as death or a large non-fatal myocardial infarction, usually with ST elevation. Stent thrombosis can occur acutely (within 24 hours), subacutely (within 30 days), or as late as one year (late) or more (very late) after stent placement. We present a case of very late stent thrombosis 59 months after stent placement and review the literature.

   Case Presentation Top

A 41-year-old Arab male with history of diabetes, hypertension, dyslipidemia, and coronary artery disease presented with exertional angina. He had undergone multivessel percutaneous coronary intervention (PCI) in another country in September 2005 for effort angina symptoms. A 2.75 × 28 mm sirolimus-eluting stent (Cypher stent) (SES) was deployed in the left anterior descending artery (LAD). Three Cypher stents (3.5 × 28 mm proximal, 3 × 33mm mid and 3 × 33 mm distal) were implanted in the right coronary artery (RCA). A Cypher stent (2.75 × 33 mm) was deployed in the posterolateral branch.

He was asymptomatic since the PCI. A routine CT coronary angiogram performed in June 2009 showed no evidence of restenosis or thrombosis. He was taking clopidogrel 75 mg/day for a year, stopped and then continued only with aspirin 75 mg/day. He was on lisinopril, atorvastatin along and oral antidiabetic medication.

During the last week of July 2010, the patient was seen in the cardiology clinic. He complained of 2 weeks history of typical exertional angina NYHA class II. The electrocardiogram showed minor T inversion in leads III and AVF. His Troponin T was negative and a transthoracic echocardiogram was normal.

After receiving loading doses of aspirin (300 mg) and clopidogrel (600 mg), he underwent a coronary angiogram which showed patency of the LAD, but RCA stents demonstrated multiple thrombi in the mid-to-distal stent segments with thrombolysis in myocardial infarction (TIMI) 2 antegrade flow [Figure 1]. Intravenous tirofiban bolus was administered followed by tirofiban and unfractionated heparin infusion for 24 h. He underwent PCI the following next day. A coronary guide wire was passed easily into the distal vessel. Multiple balloon inflations were performed within the stent using a 3 × 15 mm balloon to pulverize the large clots [Figure 2]a. This restored the TIMI 3 antegrade flow with disappearance of thrombus, obviating the need for additional stent placement [Figure 2]b. There was no apparent evidence of in-stent restenosis, stent fracture, or late-acquired malapposition, but the distal and proximal RCA stents appeared to be mildly underexpanded. Hence these two stents were treated with high-pressure balloon dilatation [Figure 3]a and b.
Figure 1: Coronary angiogram (a-c) showing multiple in-stent filling defects in mid-to-distal right coronary artery stent segments with a TIMI 2 flow, in a patient with sirolimus-eluting stent thrombosis

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Figure 2: Coronary angiogram showing balloon angioplasty of the right coronary artery in-stent thrombi (a) followed by restoration of a TIMI 3 grade flow and disappearance of thrombi (b), in a patient with sirolimus-eluting stent thrombosis

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Figure 3: Coronary angiogram showing balloon dilatation of proximal (a) and distal (b) underexpanded sirolimus-eluting stents in the right coronary artery and the final angiographic result with a TIMI 3 grade flow and no residual thrombus (c)

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The final angiogram showed excellent results with no residual thrombus and TIMI-3 flow [Figure 3]c. Post-procedure, the patient received heparin and tirofiban infusion for 24 h. The patient had an uneventful recovery and was discharged on aspirin (300 mg/day) and clopidogrel (75 mg/day) indefinitely. Platelet functional assays were not available to assess for evidence of aspirin and/or clopidogrel resistance. Routine blood tests along with thrombophilia profile were normal.

   Discussion Top

Stent thrombosis (ST) is a rare but usually a catastrophic event, frequently associated with large myocardial infarction or death. [1] The rate of early stent thrombosis (<30 days) (EST) appears to be similar in both DES and bare-metal stents (BMS), remaining below 1%. In the BASKET-LATE (Basel Stent Kosten Effektivitäts Trial-Late Thrombotic Events) study, the rates of late stent thrombosis (> 30 days) (LST) were higher in the DES group (2.6 vs. 1.3% BMS group) as well as major adverse cardiac events (4.9% DES group vs. 1.3% BMS group). [2] Metaanalysis of randomized trials suggest approximately 0.5% increased risk of very late stent thrombosis (>12 months) (VLST) with DES. [3],[4],[5]

The exact pathophysiology of VLST is unknown. The recognized independent predictors for ST in the "real world" include premature antiplatelet discontinuation, acute coronary syndrome, renal failure, diabetes, present malignancy, younger age, low ejection fraction, bifurcation lesions, long stents, undersizing of the coronary stent, TIMI flow grade <3, the presence of intermediate coronary artery disease proximal and distal to the culprit lesion, residual dissection, stent underexpansion and in-stent restenosis. [1],[6],[7],[8] Even though cessation of dual antiplatelet therapy is one of the commonest causes for ST, it has been observed that VLST tends to occur despite dual antiplatelet therapy or after long periods of clopidogrel discontinuation (as in this patient) and without a clear relationship to the usual technical or lesion risk factors associated with EST. [1] Furthermore, events continue to occur at similar rates (0.6% per year) up to 3 years. [8]

DESs reduce restenosis by inhibiting neointimal hyperplasia, but at the cost of delaying the healing process far beyond the 3 to 6-month period usually required with BMSs. DESs expose the vessel wall to antiproliferative drugs and drug-eluting platforms, with variable effects on endothelial regeneration and function. Endothelial dysfunction and incomplete neointimal coverage of stent strut remain the basic underlying mechanisms responsible for ST in DES. It is noted that presence of incomplete late stent apposition along with delayed or absent stent strut endothelialization and persistent chronic inflammation (late hypersensitivity to DES polymer) are possible mechanisms for VLST. [1],[9] In a recent meta-analysis of late stent malapposition (procedural or acquired) using intravascular ultrasound, the risk of malapposition was four times higher and the risk of VLST was six times higher in DES compared with BMS. [10]

In a recent study from the SES registry, total stent length per lesion per patient had significant impacts on target lesion revascularization rates. Longer total stent length per patient (>55 mm) was associated with increased incidence of stent thrombosis through 3 years. [11] In the case presented, the total stent length for the patient was 155 mm which could have increased his risk for VLST. In another similar study, stent lengths ≥31.5 mm were associated with significantly higher rates of ST (4.0 vs. 0.7%), death (5.2 vs. 3.0%), and myocardial infarction (2.4 vs. 0.7%) at 3 years, as compared with stent lengths <31.5 mm. [12] This patient has three stents >31.5 mm.

In addition, poor biological response to aspirin and/or clopidogrel is also frequent in clinical settings such as diabetes, obesity, and acute coronary syndromes. The theory of aspirin and clopidogrel resistance is currently accepted, although with limitations due to the different methods used to assess platelet response. [13]

In the recently published RESTART (Registry of Stent Thrombosis for Review and Reevaluation) registry, involving SES-associated ST, demographic factors associated with EST, LST and VLST were different. Factors associated with LST and VLST were hemodialysis, end-stage renal disease not on hemodialysis, the absence of left circumflex coronary artery target lesion, target lesion of chronic total occlusion, any previously performed PCI, and age <65 years. [14] In addition, history of heart failure, insulin-dependent diabetes mellitus, and low body mass index were associated with LST when compared with VLST.

Overall, clinical presentation of all types of ST was ST-segment elevation (69%) and non-ST-segment elevation (23%) acute coronary syndrome, and cardiac arrest or ventricular fibrillation in 8% of patients. In the DESIRE (Drug-Eluting Stents in the Real World) late registry with >4 years follow-up, event-free survival and cumulative incidence of definite/probable ST were 85% and 1.7%, respectively. Independent predictors of VLST were PCI in the setting of acute myocardial infarction, DES overlapping, treatment of multivessel disease, presence of moderate-to-severe calcification at the lesion site, and in-stent residual stenosis. [15] In the case presented, there were no significant clinical risk factors for VLST that are mentioned above, except for age <65 years. The lesion risk factors were long length of the stents per patient was well as per lesion with DES overlapping and underexpansion. The other possible risk factor could be stent malapposition that was not apparent visually, but could have been picked up if intravascular ultrasound was available.

Even though, he had extensive thrombus, he did not present with myocardial infarction, which is unusual. In the RESTART registry, 52% of patients in the LST group and 21% of patients in the VLST group, taking aspirin and thienopyridine developed ST. In another study, the incidence of ST at 30 days was 0.5%, 0.8% at 1 year, and 1.2% at 4 years of DES implantation. [16] Discontinuation of clopidogrel therapy was significantly associated with ST only in the first 6 months after the procedure. [8],[16] This suggests that continuing dual antiplatelet therapy alone does not prevent VLST. Hence, there is a need for novel stent designs as well as newer therapeutic strategies in preventing late and very late stent thrombosis among patients receiving drug-eluting stents.

   References Top

1.Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Academic Research Consortium. Clinical end points in coronary stent trials: A case for standardized definitions. Circulation 2007;115:2344-51.  Back to cited text no. 1
2.Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, et al. BASKET-LATE Investigators. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: An observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006;48:2584-91.  Back to cited text no. 2
3.Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007;356:998-1008.  Back to cited text no. 3
4.Kastrati A, Mehilli J, Pache J, Kaiser C, Valgimigli M, Kelbaek H, et al. Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med 2007;356:1030-9.   Back to cited text no. 4
5.Bavry AA, Kumbhani DJ, Helton TJ, Borek PP, Mood GR, Bhatt DL. Late thrombosis of drug-eluting stents: A meta-analysis of randomized clinical trials. Am J Med 2006;119:1056-61.  Back to cited text no. 5
6.de la Torre-Hernandez JM, Alfonso F, Hernandez F, Elizaga J, Sanmartin M, Pinar E, et al; ESTROFA Study Group. Drug-eluting stent thrombosis: Results from the multi-center Spanish registry ESTROFA. J Am Coll Cardiol 2008;51:986-90.  Back to cited text no. 6
7.van Werkum JW, Heestermans AA, Carla Zomer A, Kelder JC, Suttorp MJ, Rensing BJ, et al. Predictors of coronary stent thrombosis: the Dutch stent thrombosis registry. J Am Coll Cardiol 2009;53:1399-409.  Back to cited text no. 7
8.Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, et al. 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;369:667-78.  Back to cited text no. 8
9.Cook S, Ladich E, Nakazawa G, Eshtehardi P, Neidhart M, Vogel R, et al. Correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis. Circulation 2009;120:391-9.  Back to cited text no. 9
10.Hassan AK, Bergheanu SC, Stijnen T, van der Hoeven BL, Snoep JD, Plevier JW, et al. Late stent malapposition risk is higher after drug-eluting stent compared with bare-metal stent implantation and associates with late stent thrombosis. Eur Heart J 2010;31:1172-80.  Back to cited text no. 10
11.Shirai S, Kimura T, Nobuyoshi M, Morimoto T, Ando K, Soga Y, et al. J-Cypher Registry Investigators. Impact of multiple and long sirolimus-eluting stent implantation on 3-year clinical outcomes in the j-Cypher Registry. JACC Cardiovasc Interv 2010;3:180-8.  Back to cited text no. 11
12.Suh J, Park DW, Lee JY, Jung IH, Lee SW, Kim YH, et al. The relationship and threshold of stent length with regard to risk of stent thrombosis after drug-eluting stent implantation. JACC Cardiovasc Interv 2010;3:383-9.  Back to cited text no. 12
13.Coccheri S. Antiplatelet drugs--do we need new options? With a reappraisal of direct thromboxane inhibitors. Drugs 2010;70:887-908.  Back to cited text no. 13
14.Kimura T, Morimoto T, Kozuma K, Honda Y, Kume T, Aizawa T, et al. RESTART Investigators. Comparisons of baseline demographics, clinical presentation, and long-term outcome among patients with early, late, and very late stent thrombosis of sirolimus-eluting stents: Observations from the Registry of Stent Thrombosis for Review and Reevaluation (RESTART). Circulation 2010;122:52-61.  Back to cited text no. 14
15.Costa JR Jr, Sousa A, Moreira AC, Costa RA, Cano M, Maldonado G, et al. Incidence and predictors of very late (>or=4 years) major cardiac adverse events in the DESIRE (Drug-Eluting Stents in the Real World)-Late registry. JACC Cardiovasc Interv 2010;3:12-18.  Back to cited text no. 15
16.Schulz S, Schuster T, Mehilli J, Byrne RA, Ellert J, Massberg S, et al. Stent thrombosis after drug-eluting stent implantation: Incidence, timing, and relation to discontinuation of clopidogrel therapy over a 4-year period. Eur Heart J 2009;30:2714-21.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3]

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