Very late thrombosis of a paclitaxel-eluting stent after 72 months in a patient on dual anti-platelet therapy

Article (PDF Available) · April 2012with7 Reads
DOI: 10.5830/CVJA-2011-022 · Source: PubMed
Abstract
Very late thrombosis continues to be a major cause of concern in the era of drug-eluting stents. The duration of vulnerability to this complication remains undefined. A 62-year-old diabetic male underwent primary percutaneous coronary intervention with a Taxus Express stent (Boston Scientific, Natick, Mass) implantation in 2003 for anterior wall myocardial infarction (AWMI). The patient was on dual anti-platelet treatment. He was asymptomatic and his stress test was negative in 2008. After 72 months, the patient was admitted with acute AWMI resulting from stent thrombosis, which was treated successfully. This case underscores the importance of realising that very late stent thrombosis may occur when patients present with angina symptoms.
CARDIOVASCULAR JOURNAL OF AFRICA Vol 23, No 3, April 2012
AFRICA
e9
Very late thrombosis of a paclitaxel-eluting stent after
72 months in a patient on dual anti-platelet therapy
V SUBBAN, L KALIDOSS, MA SANKARDAS
Abstract
Very late thrombosis continues to be a major cause of
concern in the era of drug-eluting stents. The duration of
vulnerability to this complication remains undefined. A
62-year-old diabetic male underwent primary percutaneous
coronary intervention with a Taxus Express stent (Boston
Scientific, Natick, Mass) implantation in 2003 for anterior
wall myocardial infarction (AWMI). The patient was on dual
anti-platelet treatment. He was asymptomatic and his stress
test was negative in 2008. After 72 months, the patient was
admitted with acute AWMI resulting from stent thrombosis,
which was treated successfully. This case underscores the
importance of realising that very late stent thrombosis may
occur when patients present with angina symptoms.
Keywords: very late stent thrombosis, drug-eluting stent, Taxus
Express stent
Submitted 29/12/10, accepted 31/5/11
Cardiovasc J Afr 2012; 23: e9–e11 www.cvja.co.za
DOI: 10.5830/CVJA-2011-022
Drug-eluting stents (DES) are widely used in contemporary
practice and this has made percutaneous coronary intervention
(PCI) an accepted treatment for diabetic patients and those
with complex coronary artery disease.
1
Drug-eluting stents
effectively suppress neo-intimal hyperplasia and resulting
restenosis, but inadequate stent endothelial coverage results in
late stent thrombosis (LST). The exact period of time required
for complete neo-intimal healing and susceptibility to stent
thrombosis is largely unknown.
2
Here we report a case of very
late stent thrombosis 72 months after primary percutaneous
intervention (primary PCI) to the left anterior descending
coronary artery (LAD).
Case report
A 62-year-old diabetic male suffered an anterior wall ST-elevation
myocardial infarction in 2003. The patient was taken up for
primary PCI. The angiogram showed the right coronary artery
with no significant stenosis and a totally occluded LAD after the
first septal branch.
The LAD lesion was pre-dilated with a 2 × 10-mm Maverick
balloon (Boston Scientific Corporation, Natick, Massachusetts)
and then a 2.75 × 32-mm Taxus Express stent (Boston Scientific
Corporation, Natick, Massachusetts) was implanted, with good
angiographic results.
The peri-procedural period was uneventful. The patient was
continued on aspirin, clopidogrel and statin. The ejection fraction
with echocardiography was 48% on discharge. The patient
was on regular follow up with an indefinite dual anti-platelet
regimen. His stress test was negative for inducible ischaemia in
2008.
The patient presented to the emergency department in
October 2009 with a history of chest discomfort of two hours’
duration. The electrocardiogram showed ST-segment elevation
from V1-V6. The echocardiogram revealed regional wall motion
Institute of Cardio-Vascular Diseases, Madras Medical
Mission, Chennai, India
V SUBBAN, MD, DM, drv jay1977@yahoo.com
L KALIDOSS, MD, DM
MA SANKARDAS, MD, DM
A B C
Fig. 1. Left coronary artery angiogram in the antero-posterior cranial (A), right anterior oblique caudal (B), and left
anterior oblique caudal (C) views, showing the totally occluded left anterior descending coronary artery at the proxi-
mal end of the stent.
Case Report
CARDIOVASCULAR JOURNAL OF AFRICA Vol 23, No 3, April 2012
e10
AFRICA
abnormality in the LAD territory and the ejection fraction was
34%. The patient was loaded with 600 mg of clopidogrel and 325
mg of aspirin and was taken up for primary PCI.
The left coronary angiogram with a 6 Fr JL 3.5 guiding
catheter (Medtronic, Inc. Minneapolis, MN) showed a totally
occluded LAD at the proximal end of the stent (Fig. 1).
The lesion was easily crossed with a 0.14˝ Balance Middle
Wight universal guide-wire (Abbott Vascular, Santa Clara, CA).
Intravenous eptifibatide was started.
Thrombosuction was done with a 6 Fr Export XT catheter
(Medtronic, Inc, Minneapolis, Minnesota), which recovered
a substantial amount of thrombus (Fig. 2) and established
thrombolysis in myocardial infarction TIMI-3 distal flow with
minimal haziness at the proximal end of the stent. The stent
segment was dilated serially with a 3 × 10-mm Sprinter balloon
catheter (Medtronic, Inc, Minneapolis, Minnesota) at 9–10
atmospheric pressure. The final angiogram showed TIMI-3 distal
flow (Fig. 3). The patient had good ST-segment resolution.
The peri-procedural period was uneventful. The patient
was discharged with dual anti-platelet treatment. He was
asymptomatic at one-year follow up.
Discussion
Late stent thrombosis occurs in 0.6% of patients following
DES implantation and is associated with increased mortality,
non-fatal myocardial infarction and the need for target-vessel
revascularisation.
2
DES thrombosis is a multi-factorial process
with impaired neo-intimal healing as the common denominator.
Other proposed mechanisms of stent thrombosis, from various
autopsy and imaging studies, are stenting across major arterial
side branches, incomplete stent expansion, stent mal-apposition,
stent fracture, long stent length, stent strut penetration of
the necrotic core, disruption of vulnerable plaque near the
stent, discontinuation of dual anti-platelet therapy, anti-platelet
resistance, radiation therapy and hypersensitivity vasculitis.
3
The process of neo-intimal healing, characterised by
development of an endothelialised layer of smooth muscle cells
and extracellular matrix completely covering the stent struts, is
delayed and incomplete after the implantation of drug-eluting
stents due to the inhibitory properties of the drugs. This has been
demonstrated repeatedly in autopsy and angioscopic studies.
3
In the angioscopic follow-up study by Awata et al., incomplete
neo-intimal covering with uncovered stent struts was seen
after two years, following sirolimus-eluting stent implantation,
whereas neo-intimal covering was complete with bare-metal
stents after six months. They also demonstrated yellow plaques
beneath the stent struts. However, none of their patients had stent
thrombosis as all were on dual anti-platelet therapy throughout
the period of follow up.
4
Chen et al., in their study on sirolimus-eluting stents with
optical coherence tomography (OCT), have shown similar
findings.
5
Velero et al. reported a case of stent thrombosis 53
months after sirolimus stent implantation. With OCT, they
reported uncovered stent struts with overlying thrombi after a
long period of time. They also showed lipid-rich plaque distal to
the stent border.
6
In our case, even though DES was implanted in the setting
of acute ST-elevation myocardial infarction, the procedure was
uneventful and the patient was asymptomatic for six years. The
patient continued to be on dual anti-platelet therapy until the
day of the event. The mechanism of stent thrombosis was not
clear in our patient. Intravascular ultrasound and OCT were not
performed due to unavailability. Focal thrombotic obstruction in
the vicinity of the proximal end of the stent may have been due
to unstable plaque rupture in this area.
Plaques covered with dysfunctional endothelium forming,
despite administration of an anti-mitotic drug and persistent
Fig. 2. Two pieces of aspirated thrombus using the
Export catheter.
Fig. 3. Final angiogram in the antero-posterior cranial (A), right anterior oblique caudal (B), and left anterior oblique
caudal (C) views, showing TIMI-3 distal flow.
A B C
CARDIOVASCULAR JOURNAL OF AFRICA Vol 23, No 3, April 2012
AFRICA
e11
polymer, are more common in the peri-stent area. These plaques
are prone to rupture even long after the implantation of drug-
eluting stents.
4,6
To the best of our knowledge, this case is the longest reported
event of thrombosis following implantation of a paclitaxel-
eluting stent on dual anti-platelet therapy.
Conclusion
Stent thrombosis is an infrequent but serious event with
devastating consequences. It may occur years after implantation
of first-generation DES, even on dual anti-platelet therapy, as in
our case. In future, new-generation DES and biodegradable stents
with enhanced vessel-healing properties may prevent late stent
thrombosis. Currently, appropriate patient selection, optimal stent
deployment, long-term dual anti-platelet therapy, assessment of
anti-platelet responsiveness, and aggressive treatment of risk
factors may reduce the incidence of this complication.
References
1. Garg S, Serruys PW. Coronary stents current status. J Am Coll Cardiol
2010; 56: S1–42.
2. Windecker S, Meier B. Late coronary stent thrombosis. Circulation
2007; 116: 1952–1965.
3. Farb A, Burke AP, Kolodgie FD, Virmani R. Pathological mechanisms
of fatal late coronary stent thrombosis in humans. Circulation 2003;
108; 1701–1706.
4. Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T,
Iida O, Sera F, Nanto S, Hori M, Nagata S. Serial angioscopic evidence
of incomplete neointimal coverage after sirolimus-eluting stent implan-
tation: Comparison with bare-metal stents. Circulation 2007; 116:
910–916.
5. Chen BX, Ma FY, Luo W, Ruan JH, Xie WL, Zhao XZ, et al.
Neointimal coverage of bare-metal and sirolimus eluting stents evalu-
ated with optical coherence tomography. Heart 2008; 94: 566–570.
6. Valero SJ, Moreno R, Recalde AS. Very late drug-eluting stent throm-
bosis related to incomplete stent endothelialization. J Invasive Cardiol
2009; 21: 488–490.
    • "In the future, we plan to create a model based on the setting of the current model that is capable of simulating the consequences of drug-eluting stent deployment. In that model, the proliferation and migration of SMC will not be so important while anti-platelet drugs will have an important role70717273. This drug-eluting stent model may be used to investigate the consequences of novel approaches and new technologies. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development. Methods: The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature. Results: The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations. Conclusion: We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on the characteristics of the vessel cross-section and stent. A further development of this model could ultimately be used as a predictive tool to depict patient outcomes and inform treatment options.
    Full-text · Article · Apr 2014
  • undefined · undefined
  • undefined · undefined