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Coronary artery stent thrombosis: Incidence and risk factors
Authors: Donald Cutlip, MD, J Dawn Abbott, MD, FACC

Section Editors: Christopher P Cannon, MD, Stephan Windecker, MD
Deputy Editor: Gordon M Saperia, MD, FACC
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2018. | This topic last updated: Jul 03, 2018.
INTRODUCTION — Coronary artery stents are used in the majority of patients who undergo percutaneous
coronary intervention (PCI), as they significantly reduce the need for repeat target vessel revascularization
compared to balloon angioplasty. (See "Intracoronary stent restenosis", section on 'Incidence of restenosis'.)
Stent thrombosis is an uncommon but serious complication that almost always presents as death or a large non-
fatal myocardial infarction (MI), usually with ST elevation. It is estimated that less than 10 percent of cardiac
deaths after stent placement are attributable to stent thrombosis, with most of the remainder being due to
disease progression [1]. This issue is discussed in detail separately. (See "Clinical use of intracoronary bare
metal stents", section on 'BMS compared with DES'.)
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. Stent thrombosis within the first year appears to occur with similar
frequency in patients with bare metal stents (BMS) or drug-eluting stents (DES), as long as patients are treated
with dual antiplatelet therapy (aspirin plus a platelet P2Y12 receptor blocker) for the recommended duration. The
period of risk requiring dual antiplatelet therapy (DAPT) is longer with DES, due at least in part to delayed
neointimal coverage, although this difference is decreasing with newer generation DES. (See 'Very late stent
thrombosis' below.)
General issues related to stent thrombosis will be reviewed in this topic. The prevention and management of
stent thrombosis are discussed separately. (See "Long-term antiplatelet therapy after coronary artery stenting in
stable patients" and "Coronary artery stent thrombosis: Clinical presentation and management".)
DEFINITIONS — Although earlier clinical trials posed a problem for comparing stent thrombosis rates due to
non-standardized definition, since 2007 most trials have adopted the criteria and classification proposed by the
Academic Research Consortium (ARC) [2].
● Definite – Angiographic confirmation of a thrombus that originates in the stent or in the segment 5 mm
proximal or distal to the stent, with or without vessel occlusion, which is associated with acute onset of
ischemic symptoms at rest or ECG signs of acute ischemia or typical rise and fall of in cardiac biomarkers
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within 48 hours of angiography OR pathologic confirmation of stent thrombosis determined at autopsy or

from tissue obtained following thrombectomy.
● Probable – Unexplained death occurring within 30 days after the index procedure, or an MI occurring at any
time after the index procedure that was documented by ECG or imaging to occur in an area supplied by the
stented vessel in the absence of angiographic confirmation of stent thrombosis or other culprit lesion.
● Possible – Unexplained death occurring more than 30 days after the index procedure.
In the discussion that follows, studies using definitions other than ARC will be noted.
INTRAPROCEDURAL STENT THROMBOSIS — Intraprocedural stent thrombosis (IPST) is the development of

occlusive or non-occlusive new or increasing thrombus in or adjacent to a recently implanted stent before the
percutaneous coronary intervention (PCI) procedure is completed [3,4]. IPST is not included in the academic
research consortium definitions discussed above. In one rigorous study of IPST, it was further defined as any
discrete, mobile, intraluminal filling defect, with defined borders, with or without associated contrast staining or a
total occlusion with convex edges and staining [4].
Intraprocedural stent thrombosis, by definition, occurs sometime after an intracoronary stent is deployed and
before the end of the PCI. The best available data on its incidence come from an analysis of events in the
CHAMPION PHOENIX trial, which compared cangrelor to clopidogrel in patients undergoing PCI [4]. Among
10,939 patients included in the study, IPST developed in 0.8 percent. Similar incidences have been reported in
other smaller series [3,5]. (See "Antithrombotic therapy for elective percutaneous coronary intervention: Clinical
studies", section on 'Cangrelor'.)
The risk of IPST is significantly increased in patients with one or more of the following characteristics: ST- or non-
ST elevation myocardial infarction (MI) (both compared to stable angina) or thrombus at baseline (adjusted odds
ratio 1.87, 2.07, and 1.79, respectively) [4]. Additional risk factors that have been identified include ST-elevation
MI (compared to other types of acute coronary syndrome), bifurcation lesions, and thrombus at the time of the
baseline angiogram [3].
The clinical presentation and management of IPST is discussed elsewhere. (See "Coronary artery stent
thrombosis: Clinical presentation and management", section on 'Intraprocedural stent thrombosis'.)
MECHANISMS — Risk factors for the development of stent thrombosis fall into broad categories of procedural,
patient, lesion, and stent characteristics as well as the cessation of antiplatelet therapy [6]. (See 'Risk factors'
below.)
Each risk factor is likely to predispose the patient to stent thrombosis, which is characterized by platelet
activation and aggregation, by one or more of the following mechanisms:
● Persistent slow coronary blood flow (local or arterial) as occurs with dissection or hypoperfusion.
● Prior to reendothelialization, exposure of the blood to prothrombotic subendothelial constituents, such as

tissue factor, or to the stent itself.
● Failure to suppress platelet adhesion/aggregation at a time of prothrombotic risk, as occurs with premature
cessation of antiplatelet therapy or drug resistance.
TIMING AND INCIDENCE — Most cases of stent thrombosis, occur within the first 30 days after placement,
irrespective of stent type [7]. Reported rates tend to be lower in clinical trials (or meta-analyses of clinical trials)
than in registries, as trials often enroll lower risk patients. In general, we tell our patients that the rate of stent
thrombosis at one year is about one percent and that the yearly rate following one year is about 0.2 percent per
year.
Most of the data for drug-eluting stent (DES) thrombosis across populations with a broad range of risk come from
multiple registries in the era of first generation DES:
● In the Bern-Rotterdam registry, 8146 patients underwent PCI with a sirolimus- or a paclitaxel-eluting stent
(SES or PES). At three years, the cumulative incidence of angiographic stent thrombosis was 2.9 percent,
with early (acute and subacute) stent thrombosis occurring in 60 percent and late stent thrombosis (all
events after 30 days) in 40 percent [8]. After one year, the rate of stent thrombosis was 0.6 percent per year.
● In the German-Italian registry of 2229 patients who received either SES or PES, the rate of stent thrombosis
at nine months was 1.3 percent (0.8 percent with SES and 1.7 percent with PES), with 0.6 percent occurring
in 30 days and 0.7 percent beyond 30 days [9].
● In a prospective observational study that used the ARC definition, definite or probable ST occurred in 58 of
3021 (1.9 percent) patients who received either PES or SES for on- and off- (67 percent) label indications
during 18 months of follow-up [10]. Of these patients, 42 (72 percent) sustained an event within six months
of the procedure, more than half of which occurred within the first 30 days
● In the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), 42,150 patients underwent PCI
with either bare metal or drug-eluting stents [11]. During a mean follow-up of 661 days, the rate of definite
stent thrombosis was 1.2 percent, of which 50 percent were acute or subacute. The rate after one year
appeared constant out to three years at about 0.3 to 0.4 percent per year.
● In the Dutch stent thrombosis registry, 21,009 underwent PCI with either bare metal or drug-eluting stents
[12]. During a median follow-up of 31 months, ARC definite stent thrombosis was present in 2.1 percent of
which 32 percent was acute, 41 percent subacute, 13 percent late and 14 percent very late.
These data are limited by the restriction to first generation DES. (See 'Comparison of differing DES' below.)
Bare metal stents — Bare metal stent (BMS) thrombosis usually occurs within the first 24 to 48 hours (acute) or
much less often within the first month (subacute) after stent placement [13-21]. In a pooled analysis of data from
stent trials registries, stent thrombosis developed in 0.9 percent by 30 days and approximately 80 percent of
these occurred within the first two days [15]. The incidence of stent thrombosis by 30 days has ranged between
0.5 to 2.5 percent with higher rates in patient populations at higher risk [13,14,22].
Thrombotic events with BMS are uncommon after 30 days of treatment with dual antiplatelet therapy [12,23-25].
This observation is consistent with angioscopic studies that showed complete re-endothelialization by three to six
months [26,27]. In a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) of over
94,000 stent implantations, the cumulative incidence of stent thrombosis with BMS at one year was
approximately 1.1 percent [28].
Very late stent thrombosis (after one year) is uncommonly seen with BMS and is often after a repeat procedure
has been performed in the stented segment. In SCAAR, the rate of definite stent thrombosis at two years was
1.4 percent [28]. In our experience of adjudicating late and very late stent thrombosis after BMS, it is often
difficult to determine the contributing role of restenosis.
Drug-eluting stents — Similar to BMS, most episodes of drug-eluting stent thrombosis occur in the first year
and many of these within the first 30 days. In a meta-analysis of 10 randomized trials of 5030 patients comparing
PES or SES (first generation DES) to BMS, the 30-day rate of stent thrombosis (ST) in patients receiving DES
was 0.58 percent [22]. In a report of over 94,000 stent implantations in the Swedish Coronary Angiography and
Angioplasty Registry (SCAAR), the cumulative incidence of stent thrombosis with DES at one year was
approximately 0.4 to 0.8 percent [28]. In a 2006 meta-analysis of 19 randomized trials with 7060 patients, the risk
of PES or SES thrombosis was 0.7 percent with one-year follow-up [29].
Events continue after one year (very late stent thrombosis) for at least five years. In clinical trial populations, the
risk has been estimated at 0.2 to 0.3 percent per year after the first year [30], but a number of studies have
demonstrated the risk beyond one year is higher (as much as 0.6 percent per year) in routine practice settings
[11,31-34]. Ongoing inflammation and delayed healing with first generation DES were largely responsible for this
higher risk of very late stent thrombosis. Much of the safety benefit for newer generation DES is due to the
reduction in these very late events. (See 'Very late stent thrombosis' below and 'Comparison of differing DES'
below.)
The following studies illustrate the range of risk beyond one year for patients who received differing DES:
● In a 2012 publication from SCAAR, the cumulative rates of definite stent thrombosis at two years for older
DES (SES, PES, and the Endeavor zotarolimus [ZES]) and newer DES (everolimus and Endeavor Resolute
ZES) were 1.3 and 0.6 percent, respectively [28].
● In the Bern-Rotterdam registry, the annual rate of stent thrombosis was 0.4 to 0.6 percent for up to four
years in a population of 8146 individuals who underwent PCI with either SES or PES [32].
In a subsequent report from the Bern-Rotterdam registry (cohort III), the incidence rate of very late stent
definite or probable stent thrombosis (ARC definition) per 100 person-years in a cohort of 12,000 patients
with unrestricted use of DES (3819 SES, 4308 PES, 4212 EES), for these three DES were 1.6, 2.4, and 0.6
percent, respectively, during follow-up of up to four years.
In the TWENTE trial, which randomly assigned nearly 1400 patients to either ZES or EES, the rate of very late
definite or probable stent thrombosis (between 12 and 24 months) was 0.3 percent in both groups [35]. (See
"Comparison of drug-eluting intracoronary stents", section on 'Everolimus- versus zotarolimus-eluting stents'.)
Impact of ACS — The intracoronary and systemic prothrombotic environment accompanying an acute coronary
syndrome (ACS) has led to concerns regarding a possible increase in the risk of ST compared to patients with
stable angina. This concern has been confirmed in analyses of the ACUITY AND TRITON-TIMI 38 trial
databases [36,37]. The range of rates of early stent thrombosis (<30 days) in patients with stable angina or an
ACS according to the Academic Research Consortium definition (definite or probable) has been summarized as
follows [38]:
● Bare metal stents: 0 to 0.5, 1.4 to 1.6, and 0 to 2.9 percent (stable angina, NSTEMI and STEMI,
respectively).
● Drug-eluting stents: 0.3 to 0.4, 1.2 to 1.9, and 0 to 3.1 percent (stable angina, NSTEMI and STEMI,
respectively).
A 2012 meta-analysis of individual patient data from 11 trials found that the long-term (cumulative) rate of stent
thrombosis in patients with ACS was not significantly different between first generation DES and BMS (5.8
versus 4.3 percent, respectively) [39]. We interpret the available evidence to suggest that patients with ACS are
at greater risk of stent thrombosis than those with stable disease regardless of stent type.
RISK FACTORS — All risk factors for stent thrombosis likely work through one or more of the mechanisms
discussed above. All of these promote platelet aggregation. (See 'Mechanisms' above.)
Early and late stent thrombosis — The single most important predictor of early and late stent thrombosis is
absence of platelet P2Y12 receptor blocker therapy at the time of the event [12]. In one report, the hazard ratio
for premature discontinuation of clopidogrel was greater than 50 at nine months [9].
The relationship between cessation of dual antiplatelet therapy (DAPT) and cardiac events after percutaneous
coronary intervention was studied using data from 5018 patients in the PARIS registry [40]. At two years, the
overall incidence of cessation for any reason was 57.3 percent; the rates of discontinuation (clinician
recommended), interruption (stopping for less than 14 days for surgery), and disruption (due to bleeding or
noncompliance) were 40.8, 10.5, and 14.4 percent, respectively. Compared with those on DAPT, the hazard ratio
for major adverse cardiovascular events (a composite of cardiac death, definite or probable stent thrombosis,
spontaneous myocardial infarction, or clinically indicated target lesion revascularization) was significantly higher
only for those with disruption (1.50); it was significantly lower for those with discontinuation (0.63). It was
nonsignificantly higher for patients with interruption (1.41, 95% CI 0.94-2.12). (See "Long-term antiplatelet
therapy after coronary artery stenting in stable patients", section on 'Patients needing temporary
discontinuation'.) The impact of disruption on the risk of stent thrombosis was greater in the first 30 days
compared with after 30 days.
However, similar to many other preventative interventions, the optimal use of DAPT does not ensure that a
patient will not experience stent thrombosis. For example, in an observational study of over 10,000 patients
undergoing drug-eluting stent (DES) placement, those with early stent thrombosis were on DAPT 86 percent of
the time and those with late stent thrombosis were on DAPT 57 percent of the time [41]. Similar findings were
noted in the PARIS registry, in which 80 percent of the cases of definite or probable stent thrombosis occurred in
patients taking DAPT [40]. In these patients, it is likely that one or more predisposing risk factors leading to a
prothrombotic environment make it difficult for DAPT to be fully effective. (See 'Risk factors' above.)
The timing of late (events from one month to one year) or very late stent thrombosis (events after one year) in
relation to discontinuation of one or both antiplatelet agents was evaluated in a review of 161 published cases
[42]. (See 'Timing and incidence' above.) At the time of stent thrombosis, 19 patients were on aspirin and
thienopyridine, 94 were on aspirin only, 33 had aspirin and thienopyridine stopped simultaneously, and 15 had
thienopyridine stopped first and then had aspirin discontinued. The following findings were noted in the 142
patients who had discontinued at least one drug:
● In 33 patients who stopped both antiplatelet agents simultaneously, the mean time to stent thrombosis was
seven days.
● In 15 patients who had stopped a thienopyridine with no ill effect and then subsequently stopped aspirin, the
median time to stent thrombosis was seven days from the discontinuation of aspirin.
● In the 48 patients who stopped both agents, 75 percent of cases occurred within 10 days.
● In 94 patients with prior discontinuation of thienopyridine but on aspirin, the median time to event was 122
days. In this group, only 6 percent of cases occurred within 10 days.
The causes of and predictors of premature discontinuation were evaluated in a study of 1622 patients who
received at least one DES. In 234 patients (14.4 percent), one or both antiplatelet drugs (aspirin or clopidogrel)
were discontinued for at least five consecutive days during the first year after implantation [43]. Clopidogrel, as
opposed to aspirin, discontinuation occurred in the majority (11.8 percent). Among the 218 patients who
discontinued any agent and in whom the reason for discontinuation was known, the following observations were
made:
● The major causes of discontinuation were bleeding events or invasive procedures, medical decisions, or
patient decision (50 percent, 32 and 18 percent, respectively).
● Among those who discontinued due to bleeding events/invasive procedures, about half of these
discontinuations may not have been necessary, as the bleeding was minor or the upcoming procedure was
not likely to be associated with major bleeding.
● In patients who discontinued due to bleeding events/invasive procedures, predictors included renal
impairment, prior major hemorrhage, or peripheral artery disease. Long-term anticoagulant therapy,
undergoing procedures in a private hospital, and not receiving instructions were causes in those in whom a
medical decision was the cause. In patients who stopped of their own accord, being an immigrant, or using
psychotropic drugs were predictors.
The best available data on the risk factors for early (≤30 days) definite stent thrombosis in real world populations
come from two case-control studies:
● In analysis of the 21,009 patients in the Dutch Stent Thrombosis Registry, of whom 437 (2.1 percent)
presented with an ST, the most important risk factors were premature discontinuation of clopidogrel therapy
(odds ratio [OR] 36.5), under-sizing (OR 13.46), dissection (OR 6.19), TIMI flow post-PCI (OR 5.24), CAD
≥50 percent proximal of the culprit lesion (OR 4.15), malignancy (OR 3.06), no aspirin at the time of the
procedure (OR 2.82), and left ventricular ejection fraction <30 percent (OR 2.71) [12].
● In an analysis of clinical, angiographic, and genetic factors of ST in 123 patients and 246 controls on dual
antiplatelet therapy in a French registry, nongenetic independent correlates of early stent thrombosis (not
included in the genetic marker list below) were diabetes mellitus (OR 1.82, 95% CI 1.02-3.24), use of proton
pump inhibitors (OR 2.19, 95% CI 1.29-3.75), and higher clopidogrel loading doses (OR 0.73, 95% CI 0.57-
0.93) [44]. Significant independent genetic markers were CYP2C19 metabolic status (OR 1.99, 95% CI 1.47-
2.69) and the presence of either the ABCB1 3435 TT (OR 2.16, 95% CO 1.21-3.88) or ITGB3 PLA2 carriage
(OR 0.52, 95% CI 0.28-0.95) genotype.
Other important factors associated with both an increased risk of early and late ST after either bare metal or
drug-eluting stent placement include [9,12,15-18,20,21,24,29,32,37,45-52]:
● Acute coronary syndrome (ACS) and proximal left anterior descending coronary artery lesion (for early stent
thrombosis) [34]. (See 'Impact of ACS' above.)
● Side-branch stenting, diabetes mellitus, and end-stage renal disease (for late stent thrombosis) [34].
● Incomplete stent expansion (see "General principles of the use of intracoronary stents", section on 'Optimal
stenting').
● Greater stent length
● Residual plaque burden and small stent area on intracoronary ultrasound
● Small vessel caliber
● Residual thrombus or persistent dissection after stent placement
● Inflow or outflow obstruction
● Subtherapeutic periprocedural anticoagulation
● Left ventricular dysfunction
● Nonionic contrast media
● Cocaine use
● Emergent stent placement
● Prior brachytherapy
● Post-procedure TIMI flow grade <3
● No aspirin at the time of the procedure
● Malignancy
● CAD ≥50 percent proximal of culprit lesion
● Treatment of bifurcation lesions
● Multivessel disease, as shown in the SYNTAX trial [52]
● High on treatment (oral antiplatelet therapy) platelet reactivity [53], including polymorphisms in the genes
controlling hepatic enzymes involved in the metabolism of clopidogrel (see "Clopidogrel resistance and
clopidogrel treatment failure", section on 'Definitions' and "Clopidogrel resistance and clopidogrel treatment
failure", section on 'Potential explanations').
● The use of clopidogrel rather than prasugrel or ticagrelor in patients with ACS [38,54].
● The presence of uncovered stent struts (as detected by optical coherence tomography) [55].
Gastrointestinal bleeding is a risk of DAPT, and routine proton pump inhibitors are recommended in patients at
higher risk for bleeding. Some studies have raised the possibility that some proton pump inhibitors interfere with
clopidogrel’s ability to inhibit platelet function due to interference with conversion to active metabolite. This issue
is discussed in detail elsewhere. (See "Periprocedural and long-term gastrointestinal bleeding in patients
undergoing percutaneous coronary intervention", section on 'Prevention' and "Antithrombotic therapy for elective
percutaneous coronary intervention: General use", section on 'Bleeding' and "Aspirin for the secondary
prevention of atherosclerotic cardiovascular disease" and "NSAIDs (including aspirin): Primary prevention of
gastroduodenal toxicity".)
Very late stent thrombosis — The specific risk factors for very late stent thrombosis are less well defined but
relate to delayed neointimal coverage and ongoing vessel inflammation [47,56]. A probable explanation for an
increased risk of thrombosis in first generation DES compared with bare metal stent (BMS) after cessation of
antiplatelet therapy is delayed arterial healing, particularly incomplete neointimal coverage. However, rates of
very late stent thrombosis with newer generation DES, such as everolimus-eluting stent or RESOLUTE-
zotarolimus-eluting stent, are lower than earlier generation DES and possibly lower than BMS.
Documentation of very late stent thrombosis has come from real-time imaging studies using either angioscopy or
optical coherence tomography (OCT), from postmortem examination of stented segments in patients with and
without stent thrombosis, or from the histology of in-stent restenosis tissue obtained by atherectomy.
An angioscopic study of 37 consecutive stented lesions (15 sirolimus stents and 22 BMS) showed that neointimal
coverage is not complete in most patients with SES, but complete with all BMS at three to six months [26].
Delayed neointimal coverage in patients with SES was confirmed in a longer-term study of 17 SES and 11 BMS
in which angioscopy was performed at 4, 10, and 21 months [27]. There were two main findings:
● Neointimal coverage was complete in all but one of the patients with BMS at 3.6 months and in all at 10
months. In contrast, the majority of patients with SES had incomplete coverage at 21 months
● Mural red thrombi were seen only in patients with SES and incomplete neointimal coverage
Angioscopy is limited in the evaluation of the extent of neointimal coverage since it cannot quantify the proportion
or thickness of coverage. These limitations are not present with OCT, an intravascular imaging technique that
visualizes the surface of a stent with higher resolution than intravascular ultrasound (IVUS) [57,58]. (See
"Intravascular ultrasound, optical coherence tomography, and angioscopy of coronary circulation", section on
'Optical coherence tomography'.)
The mechanisms underlying very late DES thrombosis were explored using OCT in a study of 64 registry
patients. In this study, very late stent thrombosis occurred at a median of 4.7 years [58]. The leading associated
findings in descending order were malapposition, neoatherosclerosis, uncovered struts, and stent
underexpansion. These associations were similar in early- and new-generation DES.
These findings are consistent with those in two postmortem studies and analysis of atherectomy specimens
[47,56,59]. A postmortem study compared 28 stented segments with thrombus to 34 without thrombus in 46
patients who died more than 30 days after DES implantation [47]. The most powerful histologic predictor of stent
thrombosis was incomplete endothelial coverage (uncovered struts).
Similar findings were noted in the second postmortem study in which delayed arterial healing was more
pronounced in 14 DES patients with late stent thrombosis than in nine patients without stent thrombosis [56]. In
addition, patients with DES had a greater degree of delayed arterial healing and less complete re-
endothelialization than patients with BMS.
Current smoking and total stent length >28 mm have been identified as risk factors for very late stent thrombosis
[34]. Whether these play a role by influencing the rate of arterial healing is not known.
In-stent neoatherosclerosis has also been seen in many cases of very late stent thrombosis. Neoatherosclerosis
in stents, similar to native coronary vessels, is characterized by macrophage-mediated degradation of collagen
with necrotic core formation that predisposes to plaque rupture and thrombosis. In BMS, neoatherosclerosis
rarely occurs before three years and is more common in those greater than six years old [60]. In DES,
neoatherosclerosis is accelerated and can be a cause of thrombosis in stents less than two years after
implantation [61]. The frequency of neoatherosclerosis development appears similar for first and second
generation DES but may be associated with fewer unstable features with second generation devices [62]. The
factors that predispose to development of neoatherosclerosis are unknown but may involve dysfunctional
endothelium.
Other issues related to risk
On-label versus off-label use — The randomized trials demonstrating the lower rate of restenosis with DES
compared to BMS were performed in patients with single, previously untreated coronary lesions (on-label use). In
the SIRIUS trial, for example, the exclusion criteria included ostial, bifurcation, and unprotected left main lesions,
and vessels with thrombus or severe calcification; in addition, multivessel stenting was not performed and
patients with a recent MI or a left ventricular ejection fraction (LVEF) less than 25 percent were excluded [63].
There has been concern whether the risk and timing of stent thrombosis (ST) may be different for these excluded
or so-called off-label indications (more complex disease). At least two studies have suggested that the risk of ST
in patients who received BMS or DES for off-label indications is higher than for those with on-label indications at
both early and later time points [64,65]. This is not surprising, as the baseline risk of patients with off-label
indications is higher. For example, these individuals often have an acute coronary syndrome.
In previous, smaller studies, each of the more common off-label indications was found to be associated with an
increased risk of stent thrombosis. These include multivessel stenting [66], bifurcation stenting [9,67-70],
particularly with use of the crush technique [69,70], chronic total occlusions, and in-stent restenosis [67]. (See
"Percutaneous coronary intervention of specific coronary lesions" and "Intracoronary stent restenosis".)
Nonanatomic factors — A number of non-coronary clinical factors are also associated with stent thrombosis.
These include diabetes mellitus [8,9,45,67], black race [71], chronic kidney disease [9,67], acute coronary
syndrome at presentation [8], cocaine use [72,73], elevated C-reactive protein levels [74], and, in rare cases, a
hypersensitivity reaction to the stent [75]. (See "Drug-eluting intracoronary stents: General principles", section on
'Hypersensitivity reactions' and 'Impact of ACS' above.)
Incomplete stent apposition — Incomplete stent apposition, also known as stent malapposition, is defined
as the absence of stent strut contact with the underlying vessel wall (not overlying a side branch) [76]. This
phenomenon, which is identified by intravascular ultrasound (IVUS), can occur at the time of stent implantation; it
may resolve or worsen. It may also occur late (up to years) and in this setting has been attributed either to
positive remodeling (an increase in vessel diameter) whereby the vessel pulls away from the stent, or to plaque
or thrombus dissolution, such that a space forms between the stent and the vessel wall.
Two IVUS studies support an association between late incomplete stent apposition and very late stent
thrombosis in patients with DES:
● In a study of 13 patients with very late stent thrombosis and 144 controls, incomplete stent apposition was
significantly more frequent in patients (77 versus 12 percent) than controls [76].
● In a study of 23 patients with DES and seven with BMS very late stent thrombosis, stent malapposition was
seen in 74 percent of DES but none of the BMS patients [77].
COMPARISON OF DES AND BMS — Both randomized trial and observational study data have demonstrated
that the cumulative rate of stent thrombosis is similar for bare metal and the first generation drug-eluting stents
(SES and PES) at up to five years [12,78].
Similarly, the rate of early stent thrombosis is comparable between BMS and SES or PES. There may be a slight
predominance of BMS ST between 30 days and one year (late ST) and a slight preponderance of DES stent
thrombosis beyond one year (very late stent thrombosis), particularly for early generation DES such as SES and
PES [30]. There have been no randomized trials comparing second generation DES, such as everolimus-eluting
stents (EES) or RESOLUTE-zotarolimus-eluting stents (R-ZES), that were large enough to be sufficiently
powered to determine the relative rates of stent thrombosis between BMS and EES or R-ZES.
The relative rates of stent thrombosis between DES and BMS have been compared in meta-analyses. We advise
caution in the interpretation of their conclusions, due to the relatively short duration of follow-up and the fact that
the patients included in the trials are representative of only a portion of all patients treated with coronary artery
stents.
Two large meta-analyses are referred to in the sections below:
● A 2012 comprehensive network meta-analysis that included 49 randomized trials (over 50,000 patients) and
compared one DES to a BMS or to another DES (table 1) [79]. The primary endpoint in this meta-analysis
was the one year rate of definite stent thrombosis according to Academic Research Consortium (ARC)
criteria (see 'Definitions' above).
The benefit of this network meta-analysis is that indirect comparisons between DES that have not been
directly compared in a randomized trial, but have been compared with a third stent, can be made [80].
However, our confidence is not high that comparisons made in this meta-analysis are representative due to
the concerns about non-contemporaneous comparisons and other potential sources of bias.
● A 2012 analysis (Bangalore) of 77 randomized trials (of SES, PES, EES, ZES, and ZES-Resolute) with over
57,000 patients [81].
Late and one-year cumulative stent thrombosis — The overall risk of stent thrombosis at up to one year is
low for both BMS and DES as long as patients are continued on dual antiplatelet therapy with both aspirin and
platelet P2Y12 receptor blocker for the recommended duration [82,83]. (See 'Timing and incidence' above.)
Studies comparing early generation DES (SES or PES) to BMS suggested that the risk of stent thrombosis at up
to one year was comparable [25,29,84].
In the 2012 network meta-analysis, the rates of late definite stent thrombosis of SES, PES, and ZES were
comparable to BMS; however, the rate was significantly lower with the CoCr-EES compared to BMS (odds ratio
0.27) [79]. Since only two of the studies in the meta-analysis directly compared CoCr-EES to BMS, this finding
should not be considered definitive. Changes in the design of BMS over time and other unmeasured factors may
have influenced the indirect comparison of CoCr-EES to BMS in this study more so than with earlier generation
DES. In the larger 2012 meta-analysis (Bangalore), similar findings were noted, including a lower rate with EES
(56 percent lower) compared to BMS [81].
Very late and cumulative long-term stent thrombosis — Very late stent thrombosis includes events after one
year, while the cumulative rate of stent thrombosis includes all events. The rate of very late stent thrombosis with
DES between one and four years is approximately 0.6 percent with the protocol definition [1] and approximately
0.9 percent with the ARC definition [30]. (See 'Timing and incidence' above.)
Meta-analyses using the ARC definitions of definite or probable stent thrombosis have concluded that there is no
significant difference in the cumulative rate (at two or more years) of stent thrombosis between older DES (either
SES or PES) and BMS [1,30,82,84-86]. However, some [1,8,85,87] but not all studies [30,56,79] have suggested
that the rates of very late stent thrombosis are higher with these first generation DES.
The two large 2012 meta-analyses evaluated the rates of stent thrombosis at two years [79,81]. In the network
meta-analysis, EES (CoCr-EES) had a significantly lower cumulative rate of stent thrombosis compared to BMS
(odds ratio 0.35, 95% CI 0.17-0.69) [79]. The Bangalore meta-analysis came to a similar conclusion [81].
COMPARISON OF DIFFERING DES — Not all types of drug-eluting stents (DES) have been directly compared.
The evidence suggests that use of newer generation DES leads to lower rates of stent thrombosis compared to
older DES. Most of the data are for the everolimus-eluting stent (EES). There is less information available for R-
ZES, but it is possible they also have lower rates than older DES. Potential factors responsible for lower rates of
stent thrombosis with newer DES include more bio-compatible polymers, newer stent designs with thinner struts,
and lower drug dose.
Late and cumulative one-year stent thrombosis — With regard to late definite stent thrombosis, EES of both
types outperformed older E-ZES and PES, but not SES. With regard to cumulative one-year definite stent
thrombosis (the primary composite outcome), the following significant odds ratios (OR) were noted (other
comparisons between SES, PES, the two types of EES, and the two types of ZES did not achieve statistical
significance) [79]:
● CoCr-EES versus PES 0.28 (0.16-0.48)
● CoCr-EES versus SES 0.41 (0.24-0.70)
● CoCr-EES versus Re-ZES 0.14 (0.03-0.47)

● CoCr-EES versus PC-ZES 0.21 (0.10-0.44)
● PC-ZES versus SES 1.92 (1.07-3.90)
Similar findings of a lower rate of any stent thrombosis with EES, compared to SES, PES, and ZES, were found
in the Bangalore meta-analysis [81]. No significant differences in the rates of stent thrombosis at one year were
found in paired comparisons between other DES.
Very late stent and cumulative two-year thrombosis — Some [88-90], but not all [30,84,91], studies
comparing rates of stent thrombosis between SES and PES after one year found lower rates with SES.
The current body of evidence from randomized trials suggests that long-term cumulative rates of stent
thrombosis are lower with EES than SES or PES. There is some evidence to suggest this is also true for R-ZES:
● In the comprehensive network meta-analysis of randomized trials discussed above [79], no significant
differences in the rates of definite stent thrombosis comparing one DES (two types of EES, two types of
ZES, SES, and PES) to another at two years with one exception: the odds ratio comparing cobalt CoCr-EES
to PES was significant (0.34, 95% CI 0.19-0.62). A significant risk reduction remained when the analysis
evaluated two-year definite or probable stent thrombosis. Similar findings were noted in the Bangalore meta-
analysis of randomized trials [81].
● In a 2012 meta-analysis of 11 trials (16,775 patients) that compared the risk of two-year definite stent
thrombosis between EES and SES (five trials), PES (five trials) or R-ZES (one trial), the risk of definite stent
thrombosis with EES compared with pooled DES occurred in 0.5 percent versus 1.3 percent of patients
(relative risk 0.38, 95% CI 0.24-0.59) [7]. This translated into a 0.6 percent absolute risk reduction in favor of
EES [92]. Similar results were obtained using the broader definition of definite or probable stent thrombosis.
On further analysis, the lower risk with EES was found for early, late, cumulative one-year, and very late
events.
The finding of a lower rate of long-term stent thrombosis with EES compared to first generation stents is
supported by observational studies:
● In a study of 12,339 patients who received SES, PES, or EES, the cumulative incidence rate of definite stent
thrombosis during four years of follow-up was lower with EES compared with PES or SES (adjusted hazard
ratios 0.33, 95% CI 0.23-0.48 and 0.41, 95% CI 0.27-0.62, respectively) [93]. These findings remained
significant for the analysis of definite or probable stent thrombosis. Differences in the rates of stent
thrombosis were due mostly to a lower risk of stent thrombosis beyond one year (very late stent thrombosis).
● In a 2012 report from SCAAR in which newer DES (EES and Resolute ZES) were compared to older DES
(SES, PES, and, according to their classification, Endeavor ZES), the cumulative risk of definite stent
thrombosis at two years was lower with newer DES (adjusted hazard ratio 0.57, 95% CI 0.41-0.79) [11].
In a 2012 prospective observational study of 6166 unselected patients who received either EES or SES, the
rates of stent thrombosis at two years were similar (hazard ratio 1.16, 95% CI 0.47-2.84, comparing EES to SES)
[94].Rates of stent thrombosis between EES and R-ZES have been evaluated in the RESOLUTE All Comers and
TWENTE randomized trials, neither of which was powered to detect differences in these rates [95,96]. (See
"Comparison of drug-eluting intracoronary stents", section on 'Everolimus- versus zotarolimus-eluting stents'.) In
these two trials, the rates of definite or probable stent thrombosis were low and not significantly different in the
two groups at one year or later. In a pooled analysis of studies with the R-ZES including 7618 patients, the five-
year rate of stent thrombosis was 1.2 percent with an annual rate of 0.1 percent for very late stent thrombosis.
In a study of 8791 patients who were randomly assigned to either E-ZES (an older version of ZES) or a SES, the
rates of definite or probable stent thrombosis were similar at three years (1.4 versus 1.8 percent) [97].
SUMMARY
● Stent thrombosis is an uncommon but potentially life-threatening complication of the placement of an

intracoronary stent. While it can occur at any time after stent placement, the majority of events occur within
the first month irrespective of stent type. Stent thrombosis with bare metal stents (BMS) or drug-eluting
stents (DES) has been observed as long as five years after stent placement. The presentation is often with
MI, usually with ST elevation, or death. (See 'Introduction' above and 'Timing and incidence' above.)
● The premature cessation of dual antiplatelet therapy is the most important risk factor for ST. (See 'Risk
factors' above.)
● The cumulative rates of ST at one year are comparable between BMS and most DES (with the possible
exception of everolimus-eluting stents [EES], for which the rate is likely lower). (See 'Late and one-year
cumulative stent thrombosis' above.)
● At two years, the cumulative rate of ST is approximately 1.5 to 2 percent, and similar for both BMS and first
generation DES. It is likely that this risk is lower for EES. (See 'Very late and cumulative long-term stent
thrombosis' above.)
● The cumulative long-term risk of ST appears comparable among all DES, except for possibly higher risk for
PES and lower risk for EES. Given potential differences between DES for the period beyond two years,
longer-term follow-up is needed. (See 'Very late stent and cumulative two-year thrombosis' above.)
● Data are limited to make inferences regarding the risk of stent thrombosis for RESOLUTE-zotarolimus-
eluting stents (R-ZES), but available data suggest the long-term risk is similar for R-ZES and EES. (See
'Comparison of differing DES' above.)
REFERENCES
1. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary
stents. N Engl J Med 2007; 356:998.
2. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized
definitions. Circulation 2007; 115:2344.
3. Brener SJ, Cristea E, Kirtane AJ, et al. Intra-procedural stent thrombosis: a new risk factor for adverse
outcomes in patients undergoing percutaneous coronary intervention for acute coronary syndromes. JACC
Cardiovasc Interv 2013; 6:36.
4. Généreux P, Stone GW, Harrington RA, et al. Impact of intraprocedural stent thrombosis during
percutaneous coronary intervention: insights from the CHAMPION PHOENIX Trial (Clinical Trial Comparing
Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary
Intervention). J Am Coll Cardiol 2014; 63:619.
5. Chieffo A, Bonizzoni E, Orlic D, et al. Intraprocedural stent thrombosis during implantation of sirolimus-
eluting stents. Circulation 2004; 109:2732.
6. Lüscher TF, Steffel J, Eberli FR, et al. Drug-eluting stent and coronary thrombosis: biological mechanisms
and clinical implications. Circulation 2007; 115:1051.
7. Palmerini T, Kirtane AJ, Serruys PW, et al. Stent thrombosis with everolimus-eluting stents: meta-analysis
of comparative randomized controlled trials. Circ Cardiovasc Interv 2012; 5:357.
8. Daemen J, Wenaweser P, Tsuchida K, 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.
9. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful
implantation of drug-eluting stents. JAMA 2005; 293:2126.
10. Airoldi F, Colombo A, Morici N, et al. Incidence and predictors of drug-eluting stent thrombosis during and
after discontinuation of thienopyridine treatment. Circulation 2007; 116:745.
11. Lagerqvist B, Carlsson J, Fröbert O, et al. Stent thrombosis in Sweden: a report from the Swedish Coronary
Angiography and Angioplasty Registry. Circ Cardiovasc Interv 2009; 2:401.
12. van Werkum JW, Heestermans AA, Zomer AC, et al. Predictors of coronary stent thrombosis: the Dutch
Stent Thrombosis Registry. J Am Coll Cardiol 2009; 53:1399.
13. Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after
coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998;
339:1665.
14. Schühlen H, Kastrati A, Pache J, et al. Incidence of thrombotic occlusion and major adverse cardiac events
between two and four weeks after coronary stent placement: analysis of 5,678 patients with a four-week
ticlopidine regimen. J Am Coll Cardiol 2001; 37:2066.
15. Cutlip DE, Baim DS, Ho KK, et al. Stent thrombosis in the modern era: a pooled analysis of multicenter
coronary stent clinical trials. Circulation 2001; 103:1967.
16. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and
balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N
Engl J Med 1994; 331:496.
17. Leon MB, Wong SC. Intracoronary stents. A breakthrough technology or just another small step?
Circulation 1994; 89:1323.
18. Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation with
balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med 1994;
331:489.
19. Sutton JM, Ellis SG, Roubin GS, et al. Major clinical events after coronary stenting. The multicenter registry
of acute and elective Gianturco-Roubin stent placement. The Gianturco-Roubin Intracoronary Stent
Investigator Group. Circulation 1994; 89:1126.
20. Moussa I, Di Mario C, Reimers B, et al. Subacute stent thrombosis in the era of intravascular ultrasound-
guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome. J Am Coll
Cardiol 1997; 29:6.
21. Cheneau E, Leborgne L, Mintz GS, et al. Predictors of subacute stent thrombosis: results of a systematic
intravascular ultrasound study. Circulation 2003; 108:43.
22. Moreno R, Fernández C, Hernández R, et al. Drug-eluting stent thrombosis: results from a pooled analysis
including 10 randomized studies. J Am Coll Cardiol 2005; 45:954.
23. Ferrari E, Benhamou M, Cerboni P, Marcel B. Coronary syndromes following aspirin withdrawal: a special
risk for late stent thrombosis. J Am Coll Cardiol 2005; 45:456.
24. Scheller B, Hennen B, Pohl A, et al. Acute and subacute stent occlusion; risk-reduction by ionic contrast
media. Eur Heart J 2001; 22:385.
25. Ellis SG, Colombo A, Grube E, et al. Incidence, timing, and correlates of stent thrombosis with the
polymeric paclitaxel drug-eluting stent: a TAXUS II, IV, V, and VI meta-analysis of 3,445 patients followed
for up to 3 years. J Am Coll Cardiol 2007; 49:1043.

26. Kotani J, Awata M, Nanto S, et al. Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic
findings. J Am Coll Cardiol 2006; 47:2108.
27. Awata M, Kotani J, Uematsu M, et al. Serial angioscopic evidence of incomplete neointimal coverage after
sirolimus-eluting stent implantation: comparison with bare-metal stents. Circulation 2007; 116:910.
28. Sarno G, Lagerqvist B, Fröbert O, et al. Lower risk of stent thrombosis and restenosis with unrestricted use
of 'new-generation' drug-eluting stents: a report from the nationwide Swedish Coronary Angiography and
Angioplasty Registry (SCAAR). Eur Heart J 2012; 33:606.
29. Roiron C, Sanchez P, Bouzamondo A, et al. Drug eluting stents: an updated meta-analysis of randomised
controlled trials. Heart 2006; 92:641.
30. Mauri L, Hsieh WH, Massaro JM, et al. Stent thrombosis in randomized clinical trials of drug-eluting stents.
N Engl J Med 2007; 356:1020.
31. Faxon DP. Very late stent thrombosis and late target lesion revascularization: no end in sight. Circulation
2012; 125:562.
32. Wenaweser P, Daemen J, Zwahlen M, et al. 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 2008;
52:1134.
33. Jensen LO, Tilsted HH, Thayssen P, et al. Paclitaxel and sirolimus eluting stents versus bare metal stents:
long-term risk of stent thrombosis and other outcomes. From the Western Denmark Heart Registry.
EuroIntervention 2010; 5:898.
34. Kimura T, Morimoto T, Nakagawa Y, et al. Very late stent thrombosis and late target lesion revascularization
after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry. Circulation 2012;
125:584.
35. Tandjung K, Sen H, Lam MK, et al. Clinical outcome following stringent discontinuation of dual antiplatelet
therapy after 12 months in real-world patients treated with second-generation zotarolimus-eluting resolute
and everolimus-eluting Xience V stents: 2-year follow-up of the randomized TWENTE trial. J Am Coll
Cardiol 2013; 61:2406.
36. Aoki J, Lansky AJ, Mehran R, et al. Early stent thrombosis in patients with acute coronary syndromes
treated with drug-eluting and bare metal stents: the Acute Catheterization and Urgent Intervention Triage
Strategy trial. Circulation 2009; 119:687.
37. Cook S, Windecker S. Early stent thrombosis: past, present, and future. Circulation 2009; 119:657.
38. Wiviott SD, Braunwald E, McCabe CH, et al. Intensive oral antiplatelet therapy for reduction of ischaemic
events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous
coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet
2008; 371:1353.
39. De Luca G, Dirksen MT, Spaulding C, et al. Drug-eluting vs bare-metal stents in primary angioplasty: a
pooled patient-level meta-analysis of randomized trials. Arch Intern Med 2012; 172:611.
40. Mehran R, Baber U, Steg PG, et al. Cessation of dual antiplatelet treatment and cardiac events after
percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet
2013; 382:1714.
41. Kimura T, Morimoto T, Nakagawa Y, et al. Antiplatelet therapy and stent thrombosis after sirolimus-eluting
stent implantation. Circulation 2009; 119:987.
42. Eisenberg MJ, Richard PR, Libersan D, Filion KB. Safety of short-term discontinuation of antiplatelet
therapy in patients with drug-eluting stents. Circulation 2009; 119:1634.
43. Ferreira-González I, Marsal JR, Ribera A, et al. Background, incidence, and predictors of antiplatelet
therapy discontinuation during the first year after drug-eluting stent implantation. Circulation 2010;
122:1017.
44. Cayla G, Hulot JS, O'Connor SA, et al. Clinical, angiographic, and genetic factors associated with early
coronary stent thrombosis. JAMA 2011; 306:1765.
45. Urban P, Gershlick AH, Guagliumi G, et al. Safety of coronary sirolimus-eluting stents in daily clinical
practice: one-year follow-up of the e-Cypher registry. Circulation 2006; 113:1434.
46. Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature
discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER
registry. Circulation 2006; 113:2803.
47. Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis: strut
coverage as a marker of endothelialization. Circulation 2007; 115:2435.
48. Nakamura S, Colombo A, Gaglione A, et al. Intracoronary ultrasound observations during stent
implantation. Circulation 1994; 89:2026.
49. Goldberg SL, Colombo A, Nakamura S, et al. Benefit of intracoronary ultrasound in the deployment of
Palmaz-Schatz stents. J Am Coll Cardiol 1994; 24:996.
50. Colombo A, Hall P, Nakamura S, et al. Intracoronary stenting without anticoagulation accomplished with
intravascular ultrasound guidance. Circulation 1995; 91:1676.
51. Grines CL, Bonow RO, Casey DE Jr, et al. 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 2007; 115:813.
52. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery
bypass grafting for severe coronary artery disease. N Engl J Med 2009; 360:961.
53. Bouman HJ, van Werkum JW, Breet NJ, et al. A case-control study on platelet reactivity in patients with
coronary stent thrombosis. J Thromb Haemost 2011; 9:909.
54. Steg PG, Harrington RA, Emanuelsson H, et al. Stent thrombosis with ticagrelor versus clopidogrel in
patients with acute coronary syndromes: an analysis from the prospective, randomized PLATO trial.
55. Guagliumi G, Sirbu V, Musumeci G, et al. Examination of the in vivo mechanisms of late drug-eluting stent
thrombosis: findings from optical coherence tomography and intravascular ultrasound imaging. JACC
56. Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late
thrombotic risk. J Am Coll Cardiol 2006; 48:193.
57. Matsumoto D, Shite J, Shinke T, et al. Neointimal coverage of sirolimus-eluting stents at 6-month follow-up:
evaluated by optical coherence tomography. Eur Heart J 2007; 28:961.
58. Taniwaki M, Radu MD, Zaugg S, et al. Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed
by Optical Coherence Tomography. Circulation 2016; 133:650.
59. van Beusekom HM, Saia F, Zindler JD, et al. Drug-eluting stents show delayed healing: paclitaxel more
pronounced than sirolimus. Eur Heart J 2007; 28:974.
60. Yamaji K, Inoue K, Nakahashi T, et al. Bare metal stent thrombosis and in-stent neoatherosclerosis. Circ
61. Nakazawa G, Otsuka F, Nakano M, et al. The pathology of neoatherosclerosis in human coronary implants
bare-metal and drug-eluting stents. J Am Coll Cardiol 2011; 57:1314.
62. Otsuka F, Vorpahl M, Nakano M, et al. Pathology of second-generation everolimus-eluting stents versus
first-generation sirolimus- and paclitaxel-eluting stents in humans. Circulation 2014; 129:211.
63. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with
stenosis in a native coronary artery. N Engl J Med 2003; 349:1315.
64. Beohar N, Davidson CJ, Kip KE, et al. Outcomes and complications associated with off-label and untested
use of drug-eluting stents. JAMA 2007; 297:1992.
65. Win HK, Caldera AE, Maresh K, et al. Clinical outcomes and stent thrombosis following off-label use of
drug-eluting stents. JAMA 2007; 297:2001.
66. Rodriguez AE, Mieres J, Fernandez-Pereira C, et al. Coronary stent thrombosis in the current drug-eluting
stent era: insights from the ERACI III trial. J Am Coll Cardiol 2006; 47:205.
67. Kuchulakanti PK, Chu WW, Torguson R, et al. Correlates and long-term outcomes of angiographically
proven stent thrombosis with sirolimus- and paclitaxel-eluting stents. Circulation 2006; 113:1108.
68. Ong AT, Hoye A, Aoki J, et al. Thirty-day incidence and six-month clinical outcome of thrombotic stent
occlusion after bare-metal, sirolimus, or paclitaxel stent implantation. J Am Coll Cardiol 2005; 45:947.
69. Ge L, Airoldi F, Iakovou I, et al. Clinical and angiographic outcome after implantation of drug-eluting stents
in bifurcation lesions with the crush stent technique: importance of final kissing balloon post-dilation. J Am
Coll Cardiol 2005; 46:613.
70. Williams DO, Abbott JD. Bifurcation intervention: is it crush time yet? J Am Coll Cardiol 2005; 46:621.
71. Collins SD, Torguson R, Gaglia MA Jr, et al. Does black ethnicity influence the development of stent
thrombosis in the drug-eluting stent era? Circulation 2010; 122:1085.
72. Lemos PA. Hidden drugs, hidden risks--is cocaine use a new risk factor for stent thrombosis? Catheter
73. McKee SA, Applegate RJ, Hoyle JR, et al. Cocaine use is associated with an increased risk of stent
thrombosis after percutaneous coronary intervention. Am Heart J 2007; 154:159.
74. Park DW, Yun SC, Lee JY, et al. C-reactive protein and the risk of stent thrombosis and cardiovascular
events after drug-eluting stent implantation. Circulation 2009; 120:1987.
75. Nebeker JR, Virmani R, Bennett CL, et al. 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 2006; 47:175.
76. Cook S, Wenaweser P, Togni M, et al. Incomplete stent apposition and very late stent thrombosis after
drug-eluting stent implantation. Circulation 2007; 115:2426.
77. Lee CW, Kang SJ, Park DW, et al. Intravascular ultrasound findings in patients with very late stent
thrombosis after either drug-eluting or bare-metal stent implantation. J Am Coll Cardiol 2010; 55:1936.
78. Weisz G, Leon MB, Holmes DR Jr, et al. Five-year follow-up after sirolimus-eluting stent implantation
results of the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) Trial. J Am Coll Cardiol
2009; 53:1488.
79. Palmerini T, Biondi-Zoccai G, Della Riva D, et al. Stent thrombosis with drug-eluting and bare-metal stents:
evidence from a comprehensive network meta-analysis. Lancet 2012; 379:1393.
80. Ormiston JA, Webster MW. Stent thrombosis: has the firestorm been extinguished? Lancet 2012; 379:1368.
81. Bangalore S, Kumar S, Fusaro M, et al. Short- and long-term outcomes with drug-eluting and bare-metal
coronary stents: a mixed-treatment comparison analysis of 117 762 patient-years of follow-up from
randomized trials. Circulation 2012; 125:2873.
82. Lagerqvist B, James SK, Stenestrand U, et al. Long-term outcomes with drug-eluting stents versus bare-
metal stents in Sweden. N Engl J Med 2007; 356:1009.
83. Bavry AA, Kumbhani DJ, Helton TJ, Bhatt DL. What is the risk of stent thrombosis associated with the use
of paclitaxel-eluting stents for percutaneous coronary intervention?: a meta-analysis. J Am Coll Cardiol
2005; 45:941.
84. Kastrati A, Dibra A, Eberle S, et al. Sirolimus-eluting stents vs paclitaxel-eluting stents in patients with
coronary artery disease: meta-analysis of randomized trials. JAMA 2005; 294:819.
85. Spaulding C, Daemen J, Boersma E, et al. A pooled analysis of data comparing sirolimus-eluting stents
with bare-metal stents. N Engl J Med 2007; 356:989.
86. Caixeta A, Leon MB, Lansky AJ, et al. 5-year clinical outcomes after sirolimus-eluting stent implantation
insights from a patient-level pooled analysis of 4 randomized trials comparing sirolimus-eluting stents with
bare-metal stents. J Am Coll Cardiol 2009; 54:894.
87. Kastrati A, Mehilli J, Pache J, et al. Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal
88. Kaltoft A, Jensen LO, Maeng M, et al. 2-year clinical outcomes after implantation of sirolimus-eluting,
paclitaxel-eluting, and bare-metal coronary stents: results from the WDHR (Western Denmark Heart
Registry). J Am Coll Cardiol 2009; 53:658.
89. Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drug-eluting and bare-metal stents: a
collaborative network meta-analysis. Lancet 2007; 370:937.
90. Schömig A, Dibra A, Windecker S, et al. A meta-analysis of 16 randomized trials of sirolimus-eluting stents
versus paclitaxel-eluting stents in patients with coronary artery disease. J Am Coll Cardiol 2007; 50:1373.
91. Galløe AM, Thuesen L, Kelbaek H, et al. Comparison of paclitaxel- and sirolimus-eluting stents in everyday
clinical practice: the SORT OUT II randomized trial. JAMA 2008; 299:409.
92. Stefanini GG, Windecker S. Stent thrombosis: no longer an issue with newer-generation drug-eluting
stents? Circ Cardiovasc Interv 2012; 5:332.
93. Räber L, Magro M, Stefanini GG, et al. Very late coronary stent thrombosis of a newer-generation
everolimus-eluting stent compared with early-generation drug-eluting stents: a prospective cohort study.
94. Park DW, Kim YH, Song HG, et al. Outcomes after unrestricted use of everolimus-eluting and sirolimus-
eluting stents in routine clinical practice: a multicenter, prospective cohort study. Circ Cardiovasc Interv
2012; 5:365.
95. Silber S, Windecker S, Vranckx P, et al. Unrestricted randomised use of two new generation drug-eluting
coronary stents: 2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial.
Lancet 2011; 377:1241.
96. Serruys PW, Silber S, Garg S, et al. Comparison of zotarolimus-eluting and everolimus-eluting coronary
97. Camenzind E, Wijns W, Mauri L, et al. Stent thrombosis and major clinical events at 3 years after
zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label,
controlled trial. Lancet 2012; 380:1396.
Topic 1582 Version 23.0
GRAPHICS
Coronary artery stents approved in the United States
Polymer
(thickness) and
Name Manufacturer Stent material Drug
drug elution
kinetics
Bare metal stents
Vision Abbott Vascular Cobalt chromium – –
VeriFLEX Boston Scientific Stainless steel – –
REBEL Boston Scientific Platinum chromium
Integrity Medtronic Cobalt chromium – –
Durable polymer drug-eluting stents currently in use
EluNIR stent Cordis/Medinol Cobalt chromium Ridaforolimus PBMA/CarboSil* 7

micrometers; >50%
within 14 days and
90% by 90 days
Xience (V, Prime, Abbott Vascular Cobalt chromium Everolimus PBMA/PVDF-HFP 7.6
Xpedition) micrometers; 80%
within four weeks
Promus (Element, Boston Scientific Platinum chromium Everolimus PMAM/PVDF-HFP 7.6

Premier) micrometers; 80%
within four weeks
Resolute Medtronic Cobalt chromium Zotarolimus Biolynx* 5.6

micrometers; 85%
within eight weeks
Bioabsorbable polymer drug-eluting stents currently in use
SYNERGY Boston Scientific Platinum chromium Everolimus Poly-lactide-co-

glycide ¶ 4
micrometers; >95%
within two weeks
Previously approved drug-eluting stents
Cypher Cordis/J&J Stainless steel Sirolimus PEVA/PBMA 12.6

micrometers; >80%
within four weeks
Taxus Boston Scientific Stainless steel Paclitaxel SIBS 16

micrometers;
approximately 10%
over two weeks
Taxus Ion Boston Scientific Platinum chromium Paclitaxel SIBS 16

micrometers;
approximately 10%
over two weeks
Endeavor Medtronic Cobalt chromium Zotarolimus Phosphoryl Choline

5.3 micrometers;
95% within two
weeks
Promus Boston Scientific Cobalt chromium Everolimus PBMA/PVDF-HFP 7.6

micrometers; 80%
within four weeks
PBMA: poly(n-butyl methacrylate); PVDF-HFP: poly(vinylidene fluoride-hexafluoropropylene); PEVA: polyethylene-co-vinyl

acetate; SIBBS: poly(styrene-b-isobutylene-b-styrene).
* Proprietary polymer.
¶ Biodegradable polymer (>90% of polymer absorbed by 120 days).
Courtesy of J Dawn Abbott, MD.
Graphic 65603 Version 14.0
Contributor Disclosures
Donald Cutlip, MD Grant/Research/Clinical Trial Support: Boston Scientific [Transcatheter aortic valve;
coronary artery stent]; CeloNova [coronary artery stent]. J Dawn Abbott, MD, FACC Grant/Research/Clinical
Trial Support: AstraZeneca [CAD (Ticagrelor)]; Bristol-Myers Squib [Atrial fibrillation (Apixaban)]; Abbott [PCI
(Xience stent)]; Biosensors Research USA [PCI (Biolimus A9 stent)]. Consultant/Advisory Boards: Recor
(Adjudication committee research trial, clinical area renal denervation). Christopher P Cannon,
MD Grant/Research/Clinical Trial Support: Amgen [Lipids (Evolocumab), heart failure (Ivabradine)]; Boehringer-
Ingelheim [AF (Dabigatran), DM (Empaglifozin, Linagliptin)]; Bristol-Myers Squibb [AF (Apixaban)]; Daiichi
Sankyo [AF (Edoxaban)]; Janssen [AF (Rivaroxaban), DM (Canagliflozin)]; Merck [Lipids (Ezetimibe), DM
(Ertugliflozin, Sitaglipitin)]. Consultant/Advisory Boards: Alnylam [Lipids (Inclisiran)]; Amarin [Lipids (Vascepa
icosapent ethyl)]; Amgen [Lipids (Evolocumab), heart failure (Ivabradine)]; BI [AF (Dabigatran), DM
(Empaglifozin, Linagliptin)]; Bristol-Myers Squibb [AF (Apixaban)]; Eisai [Lipids/obesity (Locaserin)]; Janssen [AF
(Rivaroxaban), DM (Canagliflozin)]; Kowa [Lipids (Pitavastatin)]; Lipimedix [Lipids]; Merck [Lipids (Ezetimibe),
DM (Ertugliflozin, Sitaglipitin)]; Pfizer [AF (Apixaban), DM (Ertugliflozin), lipids (Atorvastatin)]; Regeneron [Lipids
(Alirocumab)]; Sanofi [Lipids (Alirocumab), ACS (Clopidogrel)], diabetes (Lixisenatide, Sotagliflozin). Stephan
Windecker, MD Grant/Research/Clinical Trial Support: Boston Scientific [General Cardiology]; St Jude Medical
[General Cardiology]; Abott [Stents (Xience)]; Amgen [Atherosclerosis (Evelocumab)]; Biotronik [Stents
(ORSIRO)]. Gordon M Saperia, MD, FACC Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

Coronary Artery Stent Thrombosis - Incidence and Risk Factors - UpToDate

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Coronary Artery Stent Thrombosis - Incidence and Risk Factors - UpToDate

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17/11/2018 Coronary artery stent thrombosis: Incidence and risk factors - UpToDate

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Coronary artery stent thrombosis: Incidence and risk factors

Authors: Donald Cutlip, MD, J Dawn Abbott, MD, FACC

within 48 hours of angiography OR pathologic confirmation of stent thrombosis determined at autopsy or

INTRAPROCEDURAL STENT THROMBOSIS — Intraprocedural stent thrombosis (IPST) is the development of

● Prior to reendothelialization, exposure of the blood to prothrombotic subendothelial constituents, such as

● Greater stent length

● Residual plaque burden and small stent area on intracoronary ultrasound

● Small vessel caliber

● Residual thrombus or persistent dissection after stent placement

● Inflow or outflow obstruction

● Subtherapeutic periprocedural anticoagulation

● Left ventricular dysfunction

● Nonionic contrast media

● Emergent stent placement

● Post-procedure TIMI flow grade <3

● No aspirin at the time of the procedure

● CAD ≥50 percent proximal of culprit lesion

● Treatment of bifurcation lesions

● Multivessel disease, as shown in the SYNTAX trial [52]

Other issues related to risk

Two large meta-analyses are referred to in the sections below:

● CoCr-EES versus PES 0.28 (0.16-0.48)

● CoCr-EES versus SES 0.41 (0.24-0.70)

● CoCr-EES versus Re-ZES 0.14 (0.03-0.47)

● CoCr-EES versus PC-ZES 0.21 (0.10-0.44)

● PC-ZES versus SES 1.92 (1.07-3.90)

● Stent thrombosis is an uncommon but potentially life-threatening complication of the placement of an

for up to 3 years. J Am Coll Cardiol 2007; 49:1043.

Topic 1582 Version 23.0

Coronary artery stents approved in the United States

Bare metal stents

Vision Abbott Vascular Cobalt chromium – –

VeriFLEX Boston Scientific Stainless steel – –

REBEL Boston Scientific Platinum chromium

Integrity Medtronic Cobalt chromium – –

Durable polymer drug-eluting stents currently in use

EluNIR stent Cordis/Medinol Cobalt chromium Ridaforolimus PBMA/CarboSil* 7

Promus (Element, Boston Scientific Platinum chromium Everolimus PMAM/PVDF-HFP 7.6

Resolute Medtronic Cobalt chromium Zotarolimus Biolynx* 5.6

Bioabsorbable polymer drug-eluting stents currently in use

SYNERGY Boston Scientific Platinum chromium Everolimus Poly-lactide-co-

Previously approved drug-eluting stents

Cypher Cordis/J&J Stainless steel Sirolimus PEVA/PBMA 12.6

Taxus Boston Scientific Stainless steel Paclitaxel SIBS 16

Taxus Ion Boston Scientific Platinum chromium Paclitaxel SIBS 16

Endeavor Medtronic Cobalt chromium Zotarolimus Phosphoryl Choline

Promus Boston Scientific Cobalt chromium Everolimus PBMA/PVDF-HFP 7.6

PBMA: poly(n-butyl methacrylate); PVDF-HFP: poly(vinylidene fluoride-hexafluoropropylene); PEVA: polyethylene-co-vinyl

Courtesy of J Dawn Abbott, MD.

Graphic 65603 Version 14.0

Conflict of interest policy

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