Coronary stent thrombosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-in-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

Stent thrombosis (ST) is a rare but devastating complication of coronary artery stenting that is associated with a high rate of morbidity and mortality ^{[1] [2] [3] [4]} This process should not be confused with restenosis, a fibro-proliferative disorder which is associated with recurrent angina and ischemia but uncommonly with myocardial infarction or death.

• Over the years stent thrombosis of bare metal stents (BMS) has been minimized by refining stent design, adopting optimal stenting strategies and improved antiplatelet medication usage from early rates of 24% ^[5] to a rare and acceptable 0.5-1.5% in the current environment.

• Following the approval by the FDA, the drug eluting stents (DES) largely replaced BMS, driven solely by the reduced revascularization with relatively little attention paid to the issue of stent thrombosis.
• Increased usage of DES and continued presentation of patients with ST beyond the first few months of implantation, coupled with the widespread awareness of ST, have led to a steady and increased stream of reporting of ST in DES.
• Recent description of frequent subclinical insitu thrombus formation within DES in the coronaries by Katani et al^[6], not only took the medical community by surprise but afforded a first hand in-vivo glimpse at the stent site itself.

• It should be noted that the term coronary stent thrombosis (ST) is commonly used for clinically significant episodes. ^[7]

• In this context, clinically significant ST appears to be a rare complication with devastating consequences if left untreated emergently, though the mileu for such probably exists in a much larger population.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

Click here to see a rare case of very late stent thrombosis, 7 years after DES implantation.

Coronary stent thrombosis (ST) is the sudden occlusion of a stented coronary artery due to formation of thrombosis. The clinical consequences of ST are frequently catastrophic and include death in 20-48% or major myocardial infarction (MI) in 60-70% of the cases.^{[1] [2] [3]}

• Some clinical trials excluded patients who underwent repeat target vessel revascularization. Given that this is more likely to be on a bare metal stent (BMS), there might have been room for bias.

• In some studies definition of late ST may have underestimated the true incidence of ST due to the exclusion of unexplained myocardial infarction (MI)s in the territory of the stented vessels and late deaths, which may have been due to stent thromboses.

• In some trials the patient who presented for revascularization of BMS patients were exluded which may have biased the interpretation of the results.

To resolve this issue and standardize the diagnosis, Academic Research Consortium(ARC) came up with the definitions of stent thrombosis^[4] which will be discussed in this section.

• Acute stent thrombosis: 0 to 24 hrs after stent implantation
• Subacute stent thrombosis: > 24 hours to 30 days after stent implantation
• Late stent thrombosis: >30 days to 1 year after stent implantation
• Very late stent thrombosis: >1 year after stent implantation

1) Angiographic confirmation of stent thrombosis: The presence of intracoronary thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent and presence of at least 1 of the following criteria within a 48-hour time window:

• Acute onset of ischemic symptoms at rest
• New ischemic ECG changes that suggest acute ischemia
• Typical rise and fall in cardiac biomarkers
• Nonocclusive thrombus-Intracoronary thrombus is defined as a (spheric, ovoid, or irregular) noncalcified filling defect or lucency surrounded by contrast material (on 3 sides or within a coronary stenosis) seen in multiple projections, or persistence of contrast material within the lumen, or a visible embolization of intraluminal material downstream.
• Occlusive thrombus-TIMI 0 or TIMI 1 intrastent or proximal to a stent up to the most adjacent proximal side branch or main branch (if originates from the side branch).

2) Pathological confirmation of stent thrombosis: Evidence of recent thrombus within the stent determined at autopsy or via examination of tissue retrieved following thrombectomy.

Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases:

• Any unexplained death within the first 30 days
• Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause.

Clinical definition of possible stent thrombosis is considered to have occurred with any unexplained death from 30 days after intracoronary stenting until end of trial follow-up.

It should be noted that the incidental angiographic documentation of stent occlusion in the absence of clinical signs or symptoms is not considered a confirmed stent thrombosis (silent occlusion).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editors-In-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

Stent thrombosis (ST) occurs due to variety of factors inducing thombogenesis. Being an invasive procedure, the trauma from coronary stenting can itself cause platelet activation and thombogenic cascade. There is either creation or an enhancement of a thrombogenic milieu by:

• Creating an environment conducive for platelet activation and/or
• Creating an environment conducive for in-stent thrombosis

These processes are facilitated by

• Creating a thrombogenic milieu by

• Slow coronary flow,
• Local dissection,
• Distal untreated critical lesion
• Poor out flow

• Persistence of, or creation of substrate for platelet activation

• Exposure of platelet activating factors due to trauma of stenting or ballooning – acutely
• Persistant incomplete endotheliazation^[1][2]
• Inadequate platelet inhibition – due to inadequate dosing or drug unresponsiveness.

• Acutely
• Subacutely
• Long term

• Dosing issues

• With anti thrombotic medications (acutely)
• Antiplatelet medications (acutely, sub-acutely or long term)
• Inadequate time for the loading dose to act
• Suboptimal/sub-therapeutic dosing during the procedure or thereafter

• Resistance to antiplatelet medications^[3]

• Aspirin resistance
• Clopidogrel resistance

• Deranged homeostasis due to disease creating a prothrombotic diathesis

• Sepsis
• Blood transfusions
• Surgery (In one study, following BMS, mortality rate among patients who had non cardiac surgery within two-weeks was 32%, almost exclusively due to ST).^[4]
• Dehydration
• Other states which may create hypotensive states. (eg. of anecdotal reports of stent thrombosis with defecation syncope)

After BMS implantation, near-complete endothelization has been shown to occur by 3 to 4 months.^[5] This coincides with the reduction of risk of ST.

Factors that serve as nidus for development stent thrombosis are:

• Delayed endothelialization^[6][1][7].
• Inflammatory response to the stent material^[8][9].
• Hypersensitivity reaction around the stent material in DES serving as nidus for ST^{[10][11][12][13][14]}.

• Antineoplastic therapy and delayed endothelialization had been an issue with late ST seen with brachytherapy^[2].
  • Coronary brachytherapy use has all but disappeared since the introduction of DES.

• An angioscopic study of stented coronary segments showed that neointimal coverage was complete only in 2 out of 15 patients with sirolimus stents and all of 22 BMS at three to six months. There were thrombi in most of the stented segments which were not seen on angiography which were more common with incomplete neointimal coverage.^[1][7] In a study involving serial angioscopy after sirolimus-eluting stent (SES) implantation at 4, 11, and 21.2 ±2.2 months showed that neointimal coverage after sirolimus-eluting stent implantation was incomplete even at that late stage.

• In a post mortem analysis, DES, compared to BMS had delayed endothelial healing. This group was more likely to have ST.^[12]

• A post mortem analysis of a patient dying from an unrelated cause but who also had a DES implanted, revealed poor endothelial cell junction formation and micro-thrombi of focal platelet aggregation at 16 months after rapamycin stent implantation.^[15]

• Evidence of an inflammatory response was present in nearly 9% of the sirolimus eluting stents (SES) and paclitaxel eluting stents (PES) by the demonstration of late aquired stent malaposition (LASMA) which was more than what was seen with BMS^[16][9].

• Cypher and Taxus DES were shown to provoke chronic eosinophilic infiltration and inflammation of the arterial wall potentially predisposing patients for thrombosis^{[10][11][12][13][14]}

• Both red and white thrombi have been demonstrated within sirolimus eluting stents (SES) as a cause of late stent thrombosis^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-in-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

A number of clinical, angiographic, and procedural factors increase the risk of stent thrombosis. Predictors of stent thrombosis can be classified into anatomic variables, procedure related variables and clinical variables. ASA and clopidogrel resistance are emerging risk factors for stent thrombosis.

Procedure related variables associated with an increased risk of stent thrombosis include ^[1].:

• Stent underexpansion
• Dissections at the stent margin
• Incomplete wall apposition
• Residual inflow and outflow disease
• Overlapping stents
• Polymer materials
• Self expanding or coil stents

Lesion-specific factors that increase the likelihood of stent thrombosis include^[1].:

• 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
• A thrombus containing lesions such as that observed in the treatment of an acute myocardial infarction

Clinical variables include^[1][2]. :

• Acute myocardial infarction
• Noncompliance and discontinuation of clopidogrel,
• Hyporesponsiveness to antiplatelet agents
• Higher baseline platelet count
• Diabetes mellitus
• Renal failure
• Congestive heart failure
• Prior radiation orbrachytherapy

Off-label indication of BMS and DES: 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.

1. Premature discontinuation of antiplatelet/clopidogrel^[6][2][7]
2. Clopidogrel resistance: Absence/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]

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

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

In a prospective study analyzing 1622 patients who received at least one DES, 14.4% discontinued at least 1 antiplatelet drug, predominantly clopidogrel with an incidence of 11.8% for at least five consecutive days during the first year post-implantation.^[1]

According to a prospective study analyzing 1622 patients^[1], the following were identified as the reason for discontinuation of one or both antiplatelet therapy:

• Nearly 50% patients had interventions or minor bleeding that did not require discontinuation.
• In patients who discontinued due to bleeding events/invasive procedures, predictors included renal impairment, prior major hemorrhage, or peripheral artery disease

32% of patients were either undergoing procedures in a private hospital or did not receive information as to who made the medical decision.

18% patients stopped antiplatelet therapy on their own accord or were on psychotropic drugs.

According to the PREMIER registry of MI patients^[2], predictors of premature thienopyridine discontinuation included:

• Older age,
• Lower level of education,
• Avoidance of healthcare because of cost,
• Unmarried marital status,
• Anemia,
• Preexisting cardiovascular disease,
• Absence of discharge instructions about the medication, and
• Lack of referral to a cardiac rehabilitation program.

In patients with DES^{[3] [4] [2] [5]}, the most important risk factor for late stent thrombosis (> 30 days to 1 year) was premature cessation (less than 6 months) of antiplatelet therapy.

• In a prospective observational cohort study^[3] of 3021 patients followed for 18 months, thienopyridine discontinuation during the first six months was the major determinant of stent thrombosis (hazard ratio 13.7). There is currently insufficient information regarding the benefit of continuing thienopyridine beyond 6 months.

• From a total cohort of 2974 consecutive patients treated with DES^[4], 38 patients presented with angiographic evidence of stent thrombosis.

• Acute ST occurred in 5 patients, subacute ST in 25 patients and late ST in 8 patients.
• Individuals who discontinued clopidogrel were more likely to sustain late stent thrombosis (36.8% versus 10.7% in those without stent thrombosis). The mean duration between cessation of clopidogrel and stent thrombosis was 153 days.

• Drug-eluting stents significantly reduce restenosis, but require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy were also evaluated in the PREMIER registry of MI patients^[2].

• Almost 14% MI patients treated with DES discontinued thienopyridine therapy at 30 days.
• Those who discontinued medication were more likely to die during the next 11 months (7.5% versus 0.7%).

The above studies suggest that dual antiplatelet therapy with thienopyridine plus aspirin for at least six months, reduces the likelihood of stent thrombosis during the first year after DES placement.

However, there is currently insufficient information available regarding the optimal duration of thienopyridine therapy. thienopyridine therapy.

Stent thrombosis (ST) has been documented in patients who have received dual antiplatelet therapy for 1 year or more and then had their thienopyridine or both their thienopyridine and aspirin discontinued^[6][7].

• In a study of 2,006 patients with DES^[8], late stent thrombosis developed in 8 cases.

• 3 cases were related to complete cessation of antiplatelet therapy,
• 2 cases occurred while patients were on aspirin therapy within one month of cessation of clopidogrel, and
• 3 cases occurred at a time when patients were apparently clinically stable on aspirin monotherapy.

There are several studies which indicate that even if aspirin therapy if used alone there is partial protection against late stent thrombosis.

• In a study of 1,236 patients hospitalized for acute coronary syndrome^[9], 20% of stent thrombosis developed after discontinuation of aspirin with mean delay between aspirin withdrawal and the acute coronary event being 10 +/- 1.9 days. This suggests that aspirin withdrawal in coronary patients may represent a real risk for the occurrence of a new coronary event.

• In an observational study in Japan^[10], 2 year outcomes were assessed in 10,778 patients undergoing sirolimus-eluting stent implantation. It was concluded that discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis.

The above studies suggest aspirin should be continued indefinitely in patients with coronary artery disease.

Class I

“1. Before implantation of drug eluting stent (DES), the interventional cardiologist should discuss with the patient the need for and duration of dual antiplatelet therapy (DAPT) and the ability of the patient to comply with and tolerate DAPT.[12] (Level of Evidence: C)”

“2. Drug eluting stent (DES) are useful as an alternative to BMS to reduce the risk of restenosis in cases in which the risk of restenosis is increased and the patient is likely to be able to tolerate and comply with prolonged dual antiplatelet therapy (DAPT). For elective PCI [13][14][15][16][17] (Level of Evidence: A); for UA/NSTEMI [15] (Level of Evidence: C); for STEMI [15][16][18][19][20] (Level of Evidence: A).”

“3. Balloon angioplasty or BMS should be used in patients with high bleeding risk, inability to comply with 12 months of dual antiplatelet therapy (DAPT), or anticipated invasive or surgical procedures within the next 12 months, during which time dual antiplatelet therapy (DAPT) may be interrupted.[21][22][2][23] (Level of Evidence: B)”

Class III (No Benefit)

“1. PCI with coronary stenting should not be performed if the patient is not likely to be able to tolerate and comply with dual antiplatelet therapy (DAPT).[21][24][25] (Level of Evidence: B)”

“2. Drug eluting stent (DES) should not be implanted if the patient is not likely to be able to tolerate and comply with prolonged dual antiplatelet therapy (DAPT) or this cannot be determined before stent implantation.[21][22][2][23] (Level of Evidence: B)”

Supportive trial data:

• A study^[26] that combined two randomized trials- REAL-LATE and ZEST-LATE analyzed 2701 patients who had received DES and had been free of major adverse cardiac or cerebrovascular events and major bleeding for a period of at least 12 months to receive clopidogrel plus aspirin or aspirin alone. The primary end point was a composite of MI or death from cardiac causes and the median duration of follow up of 19.2 months.

• The cumulative risk of the primary outcome at 2 years showed no significant difference between dual antiplatelet therapy and aspirin monotherapy (1.8% versus 1.2% respectively).
• Between the two groups there were no significant difference in the individual risks of MI, stroke, stent thrombosis, need for repeat revascularization, major bleeding, and death from any cause.
• The trial also did not study the impact of cilostazol use during the first year after DES placement^[27].

• The role for prolonged dual antiplatelet therapy (DAT) comes from observational studies and meta-analyses of randomized trials that evaluated the rates of stent thrombosis, MI or death after discontinuation of clopidogrel in patients who received DES or BMS.

• Some studies benefit associated with continuation of dual antiplatelet therapy (DAT) for longer than 12 months^{[28] [12]}, although the strongest evidence is for the maintenance of therapy during the first six months.^{[3] [10] [29] [30]}.

• An ongoing trial DAPT study is a double blind randomized controlled trial intended to determine the appropriate duration for dual antiplatelet therapy (DAPT) as well as the safety and effectiveness of DAPT to protect patients from stent thrombosis and major adverse cardiovascular and cerebrovascular events following the implantation of DES.

Premature discontinuation of dual antiplatelet therapy (DAT)is a risk factor for stent thrombosis (ST), however it is important to note that administration of dual antiplatelet therapy does not prevent the occurrence of ST and many patients are on DAT at the time of the event.

An observational study^[10] in Japan analyzed 10,778 patients undergoing sirolimus-eluting stent placement.

• Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years.

• Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of ST than those who continued both (1.76% vs 0.1% at an interval of 31 to 180 days; 0.72% vs 0.07% at an interval of 181 to 365 days; 2.1% vs 0.14% at an interval of 366 to 548 days).

Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis.

There was no apparent clinical benefit observed with thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.

Dual antiplatelet therapy which includes thienopyridine and aspirin has become the mainstay treatment strategy for prevention of stent thrombosis. As mentioned above, premature discontinuation of antiplatelet therapy markedly increases the risk of stent thrombosis, which may have catastrophic consequences. The key modifiable contributors to premature discontinuation of antiplatelet therapy are:

• Inadequate patient education and understanding about importance of compliance of antiplatelet therapy
• Drug costs
• Physician/dentists’ instructions to patients to discontinue therapy before procedures

Combined recommendations ^[31] from AHA, ACC, SCAI, ACS, ADA and ACP are as follows:

“

1. Before implantation of a stent, the physician should discuss the need for dual antiplatelet therapy. In patients not expected to comply with 12 months of thienopyridine therapy, whether for economic or other reasons, strong consideration should be given to avoiding a DES. 2. In patients who are undergoing preparation for percutaneous coronary intervention and are likely to require invasive or surgical procedures within the next 12 months, consideration should be given to implantation of a bare metal stent or performance of balloon angioplasty with provisional stent implantation instead of the routine use of a DES. 3. A greater effort by healthcare professionals must be made before patient discharge to ensure patients are properly and thoroughly educated about the reasons they are prescribed thienopyridines and the significant risks associated with prematurely discontinuing such therapy. 4. Patients should be specifically instructed before hospital discharge to contact their treating cardiologist before stopping any antiplatelet therapy, even if instructed to stop such therapy by another healthcare provider. 5. Healthcare providers who perform invasive or surgical procedures and are concerned about periprocedural and postprocedural bleeding must be made aware of the potentially catastrophic risks of premature discontinuation of thienopyridine therapy. Such professionals who perform these procedures should contact the patient’s cardiologist if issues regarding the patient’s antiplatelet therapy are unclear, to discuss optimal patient management strategy. 6. Elective procedures for which there is significant risk of perioperative or postoperative bleeding should be deferred until patients have completed an appropriate course of thienopyridine therapy (12 months after DES implantation if they are not at high risk of bleeding and a minimum of 1 month for bare-metal stent implantation). 7. For patients treated with DES who are to undergo subsequent procedures that mandate discontinuation of thienopyridine therapy, aspirin should be continued if at all possible and the thienopyridine restarted as soon as possible after the procedure because of concerns about late-stent thrombosis. 8. The healthcare industry, insurers, the US Congress, and the pharmaceutical industry should ensure that issues such as drug cost do not cause patients to prematurely discontinue thienopyridine therapy and to thus incur catastrophic cardiovascular complications.

”

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

Stents are usually placed in the proximal segments of major epicardial vessels, hence in-stent thrombotic occlusion clinically present as severe ischemia or infarction^[1].

• Emergent target lesion or target vessel revascularization is the treatment of choice in stent thrombosis to restore vessel patency.
• Revascularization may be carried out by PCI or in some instances, thrombolytics if PCI is not available ^[2].
• If revascularization is not successful, urgent CABG should be considered.

The probable cause for stent thrombosis should be evaluated as the treatment varies with etiology.

While the patient is undergoing cardiac catheterization, a careful evaluation should be undertaken to exclude procedure related variables that could be amenable to further treatment such as:

• Suboptimal stent expansion and poor apposition,
• Procedure-related variables of persistent dissection, total stent length, and final lumen diameter were significantly associated with the probability of stent thrombosis^[1].

Likewise, the patient should be questioned thoroughly for the following clinical risk factors for stent thrombosis:

• Noncompliance with dual antiplatelet therapy,
• Premature discontinuation of dual antiplatelet therapy

If neither angiographic, procedural nor clinical variables appear to play a role, then clopidogrel resistance should be considered. This diagnosis can of course be confirmed through platelet function testing and genetic testing. If this is the case consideration should be made to switching the patient to prasugrel.^[3] The TIMI 38 or TRITON trial demonstrated that newer antiplatelet agents such as prasugrel^[4] may be used after weighing the risks of bleeding against benefits of decreased recurrence of stent thrombosis/coronary events. Patients who present with stent thrombosis after completing the recommended duration of treatment with clopidogrel restarting clopidogrel 75 mg daily along with aspirin and continuing for a minimum of one year should be considered.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

Stent thrombosis(ST) is associated with a mortality rate of 25%.

• Recurrence of stent thrombosis
• Myocardial infarction secondary to stent thrombosis has worse prognosis compared to those who develop MI secondary to thrombus else where in the arteries.^[1] Stent thrombosis induced MI have higher incidence of in-hospital major cardiovascular and cerebrovascular adverse events including higher death rates.
• Death occurs in approximately 25% of patients.

• Incidence of recurrent stent thrombosis has been reported as high as 12% at 6-months.^[2]

• 1 year recurrence rate of 4.6% was reported in patients with DES.^[3]

• The Dutch stent thrombosis registry reported a 3 year recurrence rate of stent thombosis of 20.1%.^[4]

• A sub-analysis of TRITON-TIMI 38 study showed that stent thrombosis was associated with death or myocardial infarction in 89% (186/210) of patients^[5]. In follow up studies after stent thrombosis, recurrent stent thrombosis has also been noticed, especially during the following six months^[6].

• Van Werkum et al^[4] studied the long term outcome after definite stent thrombosis (ST). 431 patients with definite stent thrombosis were enrolled in this multicenter registry. The primary end point was the composite of cardiac death and definite recurrent ST. The primary end point occurred in 111 patients after a median follow-up of 27.1 months. Clinical outcome was not affected by the type of previously implanted stent (drug-eluting stent or bare-metal stent) or the category of ST (early versus late). Authors concluded that the long-term clinical outcome after a first definite ST is unfavorable, with a high mortality and recurrence rate. Diabetes mellitus, left ventricular ejection fraction < 45%, long total stent length, complex coronary lesions, TIMI flow grade < 3 after percutaneous coronary intervention, and implantation of an additional coronary stent during the emergent percutaneous coronary intervention for the ST were associated with this unfavorable outcome.

• A pooled analysis of multicenter coronary stent clinical trials showed that in patients with angiographic stent thrombosis the incidence of death or myocardial infarction was 64.4% at the time of stent thrombosis and had a 6-month mortality rate of 8.9%.^[7]

• One year mortality rate was 16% and stent thrombosis recurrence was 4.6% in a multicenter study in Spain.^[3]

• The mortality rate was 31% and MI was seen in 83% of patients with stent thrombosis at 4 years follow-up in a pooled analysis.^[8]

• In a study to investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis, 6 month major adverse clinical events were comprised of death (11%), reinfarction (16%), and recurrent stent thrombosis (12%).^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Smita Kohli, M.D.; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

The main principle of the preventive treatment for stent thrombosis is to perform the best PCI possible, including good expansion and apposition of the stent. In this context, the role of intravascular ultrasound has been studied extensively and can be helpful^[1][2].

Combined antiplatelet therapy for the preventive treatment has been extensively studied and are routinely recommended.

• There are better outcomes noted with the use of aspirin plus ticlopidine or clopidogrel than with aspirin plus warfarin or aspirin alone^{[3][4][5][6][7]}.
• Preliminary evidence suggests prasugrel resulted in fewer ischaemic outcomes including stent thrombosis than with standard clopidogrel^[8].

• In STARS trial^[3], studying 1653 patients showed superiority of aspirin and ticlopidine over combination of aspirin and warfarin or aspirin alone for reducing subacute stent thrombosis, although there were more hemorrhagic complications than with aspirin alone.

• A similar benefit for combined aspirin plus ticlopidine was noted in another randomized controlled trial^[4].

• Results from double blinded randomized studies- PCI-CURE trial^[9], analyzing 2658 patients and CREDO trial^[10], analyzing 2116 patients, revealed the benefit of clopidogrel therapy increased with time and provide evidence for at least one year therapy in patients with BMS. However both the studies did not evaluate DES.

• TRITON TIMI-38^[8]trial analyzing 12,844 patients who underwent stenting for ACS revealed intensive antiplatelet therapy with prasugrel resulted in fewer ischaemic outcomes including stent thrombosis than with standard clopidogrel.These findings were statistically robust irrespective of stent type, and the data affirm the importance of intensive platelet inhibition in patients with intracoronary stents.

The 2008 American College of Chest Physician illustrates the following guidelines for primary and secondary prevention of coronary artery disease^[11].

“

1. For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI) with stent placed, we recommend daily aspirin (75–100 mg) as indefinite therapy. (Grade 1A). 2. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). 3. For patients undergoing PCI with BMS placement following ACS, we recommend 12 months of aspirin (75–100 mg/d) plus clopidogrel (75 mg/d) over aspirin alone (Grade 1A). 4. For patients undergoing PCI with a DES, we recommend aspirin (75–100 mg/d) plus clopidogrel (75 mg/d for at least 12 months) [Grade 1A for 3 to 4 months; Grade 1B for 4 to 12 months]. Beyond 1 year, we suggest continued treatment with aspirin plus clopidogrel indefinitely if no bleeding or other tolerability issues (Grade 2C).

”

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