Acute and subacute stent thrombosis in a patient with clopidogrel resistance: a case report.
ABSTRACT Drug-eluting stents (DES) are considered the treatment of choice for most patients with obstructive coronary artery disease when percutaneous intervention (PCI) is feasible. However, stent thrombosis seems to occur more frequently with DES and occasionally is associated with resistance to anti-platelet drugs. We have experienced a case of recurrent stent thrombosis in a patient with clopidogrel resistance. A 63-year-old female patient suffered from acute myocardial infarction and underwent successful PCI of the left anterior descending coronary artery (LAD) with two DESs. She was found to be hyporesponsive to clopidogrel and was treated with triple anti-platelet therapy (aspirin 100 mg, clopidogrel 75 mg, and cilostazol 200 mg daily). Three days after discharge, she developed chest pain and was again taken to the cardiac catheterization laboratory, where coronary angiography (CAG) showed total occlusion of the mid-LAD where the stent had been placed. After intravenous administration of a glycoprotein IIb/IIIa inhibitor, balloon angioplasty was performed, resulting in Thrombolysis In Myocardial Infarction (TIMI) III antegrade flow. The next day, however, she complained of severe chest pain, and the electrocardiogram showed marked ST-segment elevation in V1-V6, I, and aVL with complete right bundle branch block. Emergent CAG revealed total occlusion of the proximal LAD due to stent thrombosis. She was successfully treated with balloon angioplasty and was discharged with triple anti-platelet therapy.
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ABSTRACT: The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent. In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2+/-5 versus 37+/-28 mm3) and percent of volume obstruction (1+/-3% versus 29+/-20%) at 6 months between the 2 groups was highly significant (P<0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition in the sirolimus group compared with the uncoated stent group (P<0.05), it was not associated with any adverse clinical events at 1 year. Sirolimus-eluting stents are effective in preventing neointimal hyperplasia without creating edge effect and without affecting the plaque burden behind the struts.Circulation 08/2002; 106(7):798-803. · 15.20 Impact Factor
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ABSTRACT: We attempted to make a comprehensive assessment of the risk of stent failure (death, myocardial infarction or angiographically documented occlusion), differentiating early (first and second weeks) and late (third and fourth weeks) events. The risk of stent failure decreases rapidly within the first week. It has been suggested that the risk rate for late events is close to 0% and that the thienopyridine regimen (ticlopidine or clopidogrel) could be safely reduced from four to two weeks, minimizing the risk of hematological complications. We analyzed 5,678 patients with successful coronary stent placement and a four-week ticlopidine regimen. The rate of stent failure was 2.5% at four weeks, with 112 early (2.0%) and 30 late events (0.5%). Multivariate analysis identified different risk factors for early versus late events. While variables on stenosis severity and procedural results that can be influenced by the operator were identified as independent risk factors for early events (percent stenosis before and after the procedure, residual dissection, length of stented segment), more clinical variables were associated with late events (age, reduced left ventricular function, systemic hypertension as a protective factor). The late-event rate was <0.1% in the absence of these factors, but it was 2.5% with all three risk factors present. The risk of late stent failure is low with a four-week ticlopidine regimen. However, high-risk subgroups have a risk of 2.5%. As this rate is presumably higher if thienopyridines are discontinued after two weeks, these data suggest that a risk stratification to a two- or four-week regimen is preferable to a general reduction.Journal of the American College of Cardiology 07/2001; 37(8):2066-73. · 14.09 Impact Factor
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ABSTRACT: We determined the prevalence and clinical predictors of aspirin resistance by prospectively studying 325 patients with stable cardiovascular disease who were receiving aspirin (325 mg/day for > or =7 days) but no other antiplatelet agents. We also compared the detection of aspirin resistance with optical platelet aggregation, a widely accepted method, with a newer, more rapid method, the platelet function analyzer (PFA)-100, a whole blood test that measures platelet adhesion and aggregation ex vivo. Blood samples were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate (ADP) and arachidonic acid, and by PFA-100 using collagen and/or epinephrine and collagen and/or ADP cartridges to measure aperture closure time. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and a mean aggregation of > or =20% with 0.5 mg/ml arachidonic acid. Aspirin semiresponders were defined as meeting one, but not both of the above criteria. Aspirin resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time (< or =193 seconds). By optical aggregation, 5.5% of the patients were aspirin resistant and 23.8% were aspirin semiresponders. By PFA-100, 9.5% of patients were aspirin resistant. Of the 18 patients who were aspirin resistant by aggregation, 4 were also aspirin resistant by PFA-100. Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women (34.4% vs 17.3%, p = 0.001) and less likely to be smokers (0% vs 8.3%, p = 0.004) compared with aspirin-sensitive patients. There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders (65.7 vs 61.3 years, p = 0.06). There were no differences in aspirin sensitivity by race, diabetes, platelet count, renal disease, or liver disease.The American Journal of Cardiology 09/2001; 88(3):230-5. · 3.21 Impact Factor
DOI 10.4070 / kcj.2009.39.10.434
Print ISSN 1738-5520 / On-line ISSN 1738-5555
Copyright ⓒ 2009 The Korean Society of Cardiology
Acute and Subacute Stent Thrombosis in a Patient
With Clopidogrel Resistance: A Case Report
Sung Soo Kim, MD1,2, Myung Ho Jeong, MD1,2, Hyun-Kuk Kim, MD1,2, Soo Young Bae, MD1, Kyoung Ho Ryu, MD1,
Kyung Hun Cho, MD1,2, Min Chul Kim, MD1,2, Keun Ho Park, MD1,2, Doo Sun Sim, MD1,2,
Young Joon Hong, MD1,2, Ju Han Kim, MD1,2, Youngkeun Ahn, MD1,2 and Jung Chaee Kang, MD1,2
1The Heart Research Center of Chonnam National University Hospital and
2Cardiovascular Research Institute of Chonnam National University, Gwangju, Korea
Drug-eluting stents (DES) are considered the treatment of choice for most patients with obstructive coronary
artery disease when percutaneous intervention (PCI) is feasible. However, stent thrombosis seems to occur more
frequently with DES and occasionally is associated with resistance to anti-platelet drugs. We have experienced a
case of recurrent stent thrombosis in a patient with clopidogrel resistance. A 63-year-old female patient suffered
from acute myocardial infarction and underwent successful PCI of the left anterior descending coronary artery
(LAD) with two DESs. She was found to be hyporesponsive to clopidogrel and was treated with triple anti-
platelet therapy (aspirin 100 mg, clopidogrel 75 mg, and cilostazol 200 mg daily). Three days after discharge, she
developed chest pain and was again taken to the cardiac catheterization laboratory, where coronary angiography
(CAG) showed total occlusion of the mid-LAD where the stent had been placed. After intravenous administra-
tion of a glycoprotein IIb/IIIa inhibitor, balloon angioplasty was performed, resulting in Thrombolysis In Myo-
cardial Infarction (TIMI) III antegrade flow. The next day, however, she complained of severe chest pain, and the
electrocardiogram showed marked ST-segment elevation in V1-V6, I, and aVL with complete right bundle
branch block. Emergent CAG revealed total occlusion of the proximal LAD due to stent thrombosis. She was
successfully treated with balloon angioplasty and was discharged with triple anti-platelet therapy. (Korean Circ J
KEY WORDS: : Thrombosis; Stents; Clopidogrel.
In recent years, drug-eluting stents (DES) have been
demonstrated to dramatically reduce the rate of reste-
nosis and the need for repeat revascularization.1-3) De-
spite these promising results, stent thrombosis seems to
occur more frequently with DES and often seems to be
associated with clopidogrel resistance.4) We report a
case of recurrent stent thrombosis associated with clo-
pidogrel resistance in a patient with acute myocardial
A 63-year-old female was transferred to the Emergency
Department complaining of squeezing chest pain that
had increased over the past twelve hours. The electrocar-
diogram (ECG) showed ST-segment elevation in V1-V3
(Fig. 1). She underwent emergent coronary angiography
(CAG), which revealed critical stenosis in the proximal
and middle left anterior descending coronary artery
(LAD). She was successfully treated with two paclitaxel-
eluting stents (3.0×12 mm and 2.5×28 mm Taxus
stents, Boston Scientific, Reading, PA, USA) in the pro-
ximal and middle LAD (Fig. 2). She was treated with tri-
ple antiplatelet therapy (aspirin 100 mg, clopidogrel 75 mg,
and cilostazol 200mg daily) because she was found to be
hyporesponsive to clopidogrel when tested for adenosine
diphosphase (ADP)-induced platelet aggregation utiliz-
ing the VerifyNow P2Y12 point-of-care assay (181/0
Received: May 28, 2009
Accepted: June 30, 2009
Correspondence: Myung Ho Jeong, MD, The Heart Research Center of
Chonnam National University Hospital, 671 Jaebong-ro, Dong-gu, Gwangju
Tel: 82-62-220-6243, Fax: 82-62-228-7174
○ cc This is an Open Access article distributed under the terms of the Creative
Commons Attribution Non-Commercial License (http://creativecommons.
org/licenses/by-nc/3.0) which permits unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work is
Sung Soo Kim, et al.·435
P2Y12 reaction unit/%).
Three days after discharge, she again developed chest
pain and presented to the emergency department with
mental confusion associated with acute pulmonary ede-
ma. The ECG showed ST-segment elevation in V1-V5
(Fig. 3) and the cardiac enzymes were elevated (creatine
kinase-MB 34.0 U/L, Troponin-I 67.01 ng/mL, Tropo-
nin-T 5.5 ng/mL). Emergency CAG, after intubation
due to hypoxemia, showed total occlusion of the mid-
LAD due to stent thrombosis (Fig. 4). After intravenous
administration of a glycoprotein IIb/IIIa receptor blocker
(ReoPro®), balloon angioplasty was carried out multiple
times using a 3.0 mm balloon at 10-12 atm because of
recurrent, immediate thrombus formation and coronary
occlusion. The next day, however, she complained of
severe chest pain again, and the ECG showed marked
ST-segment elevation in V1-V6, I, and aVL; and new-
onset complete right bundle branch block with left an-
terior fascicular block (Fig. 5). Emergent CAG revealed
thrombotic total occlusion of the proximal LAD (Fig. 6).
She was successfully treated with balloon angioplasty
and a final angiogram revealed improved flow over stent-
ed LAD without intraluminal filling defect. Despite the
cilostazol medication, ADP-induced platelet aggregation
Fig. 1. The electrocardiogram showed ST-segment elevation in V1-V3.
Fig. 2. A: coronary angiogram revealed critical stenosis in the proximal and middle left anterior descending coronary artery (LAD) (arrows).
B: two paclitaxel-eluting stents (3.0×12 mm and 2.5×28 mm Taxus stents, Boston Scientific, Reading, PA, USA) were successfully placed
in the occluded LAD.
436·Acute and Subacute Stent Thrombosis
showed that she was still hyporesponsive to clopidogrel
(171/0 P2Y12 reaction unit/%). She was discharged af-
ter uneventful recovery with triple anti-platelet therapy
using an increased dose of aspirin (aspirin 200 mg, clo-
pidogrel 75 mg, cilostazol 200 mg daily). The patient has
been followed up at the outpatient department without
We report this case to draw more attention to stent
thrombosis associated with clopidogrel resistance after
DES implantation. This case shows that a DES patient
with clopidogrel resistance can be vulnerable to stent
thrombosis even if treated with triple anti-platelet thera-
py, which in recent studies has been shown to be more
effective in preventing stent thrombosis than conven-
tional dual anti-platelet therapy. Recently, there have been
safety concerns with DES due to late stent thrombosis.
Stent thrombosis is an uncommon but serious complica-
tion of coronary artery stents that often presents as myo-
cardial infarction (MI) or death. Over several trials, the
incidence of stent thrombosis was 0.58-1.3% in DES.5)6)
Several factors have been associated with stent throm-
bosis, including older age, black race, diabetes mellitus,
bifurcation lesion, in-stent restenosis lesion, procedure-
related factors such as stent malposition, greater stent
length, postprocedure acute renal failure, non-compli-
ance to anti-platelet agent and anti-platelet resistance.7-9)
Anti-platelet resistance as an independent predictor of
stent thrombosis, even several years after implantation
of DES, increases the risk of stent thrombosis. In this
Fig. 3. The electrocardiogram showed newly developed ST-segment elevation in V1-V5.
Fig. 4. A: emergent coronary angiogram showed near-total occlusion of the mid- left anterior descending coronary artery (LAD) due to stent
thrombosis (arrow). Balloon angioplasty was carried out multiple times using a 3.0 mm balloon at 10-12 atm with the aid of platelet glyco-
protein IIb/IIIa inhibitor. B: a final coronary angiogram showed Thrombolysis In Myocardial Infarction (TIMI) III antegrade flow with some
remaining filling defects in the LAD.
Sung Soo Kim, et al.·437
patient, stent thrombosis may have been caused by sev-
eral risk factors, especially anti-platelet resistance.
The treatment of anti-platelet resistance is as yet un-
defined. Several therapeutic approaches (the addition of
cilostazol or a glycoprotein IIb/IIIa inhibitor, increased
dosage of clopidogrel and aspirin) might be taken for a
patient with anti-platelet resistance. In our patient, al-
though cilostazol (200 mg daily) was added to conven-
tional dual anti-platelet therapy, recurrent stent throm-
bosis occurred. Subsequently, the daily dose of aspirin
was increased from 100 mg to 200 mg.
In the DES era, stent thrombosis is a fatal complica-
tion and anti-platelet therapy has been shown to be very
important in preventing stent thrombosis. Thus, assess-
ment of the patient’s responsiveness to anti-platelet
agents may be a crucial factor in monitoring these drugs’
therapeutic efficacy and improving clinical outcomes af-
ter implantation of DES. Recent studies have shown
that adequate anti-platelet effects are not achieved in
5% to 45% of the patients taking aspirin and in 4% to
30% of patients taking clopidogrel10)11) and therefore
suggest that many patients are resistant or only partially
responsive to the anti-platelet agents. Currently, however,
routine screening for anti-platelet resistance remains a
persistent, unresolved issue and further evidence is neces-
sary before it will be possible to recommend this testing
as part of standard assessment of PCI candidates. In addi-
tion, further prospective studies are needed to set guide-
lines for optimal treatment of patients with antiplatelet
resistance who are at increased risk of stent thrombosis,
a catastrophic complication of DES implantation.
1) Serruys PW, Degertekin M, Tanabe K, et al. Intravascular ultra-
Fig. 5. The next day, she complained of chest pain, and the electrocardiogram showed ST-segment elevation in V1-V6, I, and aVL; and new-
onset complete right bundle branch block with left anterior fascicular block.
Fig. 6. A: emergent coronary angiogram revealed thrombotic total occlusion of the proximal left anterior descending coronary artery (LAD)
(arrow). Balloon angioplasty was performed several times using a 2.5 mm balloon. B: a final coronary angiogram showed Thrombolysis In
Myocardial Infarction (TIMI) III antegrade flow with resolution of the thrombus burden.
438·Acute and Subacute Stent Thrombosis
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