JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 9, NO. 11, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
ISSN 1936-8798/$36.00
http://dx.doi.org/10.1016/j.jcin.2016.02.025
Incidence and Clinical Outcomes
of Stent Fractures on the Basis of
6,555 Patients and 16,482 Drug-Eluting
Stents From 4 Centers
Jing Kan, MBBS,a Zhen Ge, MD,a Jun-Jie Zhang, PHD,a Zhi-Zhong Liu, PHD,a Nai-Liang Tian, MD,a Fei Ye, MD,a
Sui-Ji Li, MD,b Xue-Song Qian, MD,c Song Yang, MD,d Meng-Xuan Chen, MBBS,e Tanveer Rab, MD,f
Shao-Liang Chen, MDa
ABSTRACT
OBJECTIVES The present study aimed to analyze the incidence of SF and its correlation with clinical events after
DES implantation and the outcome of re-intervention for symptomatic in-stent restenosis (ISR) induced by stent
fracture (SF).
BACKGROUND SF is associated with a high rate of clinical events after the implantation of drug-eluting stents (DES).
However, the chronological rate of SF and the effect of SF on clinical outcomes from a large patient population
remain underreported.
METHODS A total of 6,555 patients with 16482 DES in 10751 diseased vessels and surveillance angiography between
November 2003 and January 2014 were prospectively studied. The primary endpoints included the incidence of SF,
in-stent restenosis (ISR), target lesion revascularization (TLR), and definite stent thrombosis (ST) at the end of follow-up
before and after propensity score matching. Clinical outcomes after TLR were also followed up.
RESULTS The SF rate was detected in 803 (12.3%) patients, 3,630 (22.0%) stents, and 1,852 (17.2%) diseased vessels.
SF increased over time. SF was associated with higher unadjusted rates of ISR (42.1%), TLR (24.8%, n ¼ 379), and definite
ST (4.6%) compared with stents without fracture (10.7%, 6.6%, and 1.03%, all p < 0.001), and the differences remained
significant after propensity score matching (all p < 0.05). There was no significant difference in any-cause or cardiac
mortality between patients with and without SF. After 1,523 days of follow-up since the first surveillance angiography,
repeat ISR was detected in 90 of 379 (23.8%) stents after reintervention, and 6 (7.5%) stents required repeat TLR.
CONCLUSIONS SF is more frequently observed after DES implantation. TLR was required in almost one-fourth of
fractured stents. Increased events in the SF group did not translate into a difference in mortality compared with the
non-SF group. Reintervention was associated with acceptable clinical results. (J Am Coll Cardiol Intv 2016;9:1115–23)
© 2016 by the American College of Cardiology Foundation.
T
he association of stent fracture (SF) with in-
of SF varies from <1% to >8% (3) depending on the
stent restenosis (ISR), stent thrombosis (ST),
time point measured after the index procedure, DES
and subsequent target lesion revasculariza-
types, fracture definitions, and imaging tools used
tion (TLR) is of concern (1,2), particularly in the mod-
for the analysis. Previous reports demonstrated that
ern era of drug-eluting stents (DES). The incidence
the majority of SFs occur within the first year after
From the aDivision of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; bDivision of Cardiology,
Jintan People Hospital, Jintan, China; cDivision of Cardiology, Zhangjiagang People Hospital, Jiangsu, China; dDivision of Cardiology, Yixin People Hospital, Wuxi, China; eDivision of Arts and Science, Emory College of Arts and Science, Emory University,
Atlanta, Georgia; and the fDivision of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Dr. Chen now is the fellow of the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine and Clinical
Medical Research Center of Jiangsu Province, China. All other authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
Manuscript received December 28, 2015; revised manuscript received February 3, 2016, accepted February 18, 2016.
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Kan et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 11, 2016
JUNE 13, 2016:1115–23
Stent Fracture After DES
ABBREVIATIONS
the stenting procedure (1–3). Globally, cobalt
AND ACRONYMS
chromium-based
DES = drug-eluting stent(s)
ISR = in-stent restenosis
which
feature
design,
have
second-generation
a
thin-strut
completely
and
DES,
flexible
replaced
first-
generation DES, which have a stainless steel
IVUS = intravascular
platform (1–3). However, the exact incidence
ultrasound
of SF and its correlation with clinical events
MACE = major adverse
remain unclear. The present study aimed to
cardiovascular event(s)
investigate the incidence of SF after index
MI = myocardial infarction
stenting procedure, its correlation with clin-
OCT = optical coherence
ical events, and clinical outcomes after
tomography
PCI = percutaneous coronary
repeat intervention for SF-related TLR.
intervention
Pattern I, single-strut fracture of gap between struts >2 times
SEE PAGE 1124
PSM = propensity score
2.5 m expanded cell diameter; Pattern II, incomplete transverse
stent fracture that resulted in V-shaped horizontal separation
matching
QCA = quantitative coronary
METHODS
of stent struts without discontinuity at one edge of the stent;
Pattern III, complete transverse fracture of the stent without
analysis
RCA = right coronary artery
SF = stent fracture
ST = stent thrombosis
TLR = target lesion
revascularization
F I G U R E 1 Classification of Stent Fractures
STUDY
POPULATION
AND
EXCLUSION
CRITERIA. The NFMD (Nanjing First Hospital
Medical
Data)
database,
established
in
displacement of 2 components of the fractured stent by 1 mm;
Pattern IV, complete transverse fracture of the stent with
torsion during the cardiac cycle or displacement of 2 stent
fragments >1 mm.
November 2003, in Nanjing, China, is a prospective multicenter (4 centers), all-comers
registry of patients who undergo percuta-
QUANTITATIVE
ANGIOGRAPHIC
ANALYSIS. Coronary
neous coronary intervention (PCI). By January 2014,
angiography was performed after the intracoronary
this database included 10,077 PCIs (2,793 staged PCIs)
administration of 0.2 mg nitroglycerin. Quantitative
for 8,602 patients. Routine follow-up angiography at
angiographic analysis was performed before and after
9 to 12 months post-procedure was encouraged for all
stenting and during the follow-up angiography using
patients. The current study complied with the
a guide catheter to calibrate the magnification and a
Declaration of Helsinki regarding investigations in
validated
humans and was approved by the institutional ethics
(CASS 5.7, Pie Medical Imaging, Maastricht, the
committees at the 4 participating centers. There was
Netherlands). The analyses were performed indepen-
no industry involvement in the design, conduct, or
dently by 2 experienced observers who were blinded
analysis of the study. All of the study patients gave
to the clinical information. The target lesion for
written informed consent for the procedure and the
measurement of the minimal luminal diameter
follow-up protocol.
included 5 mm margins proximal and distal to the
automated
edge
detection
algorithm
For this analysis, the exclusion criteria (Figure 1)
stent and the stent itself. ISR was defined as a percent
included: 1) bare-metal stent use (n ¼ 186); and 2)
diameter stenosis of >50% within the stent at the time
poor quality of angiographic images (n ¼ 12). A total of
of follow-up within the stented segment or within 5
6,555 patients with 10,751 diseased vessels (with
mm proximal or distal to the stent segment. The
16,482 DES implanted) and repeat angiography (>30
angiographic ISR patterns were classified I to IV ac-
days after stenting procedure) were included in this
cording to Mehran’s classification (4). A hinge motion
analysis.
lesion was defined as having a $16 difference in the
STENTING PROCEDURE. All interventions were per-
formed using standard techniques. Pre-dilation, post-
angle between diastole and systole before the
procedure.
dilation, and the use of intravascular ultrasound
STUDY ENDPOINTS AND DEFINITIONS. The study’s
(IVUS) (Boston Scientific, Marlborough, Massachu-
primary endpoints were the chronological incidence
setts) or optical coherence tomography (OCT) (S7, St.
of SF, ISR, clinically driven target lesion revasculari-
Jude Medical, St. Paul, Minnesota; since 2013) were
zation (TLR), and definite/probable ST at the end of
decided on the basis of the operator’s discretion.
follow-up (January 2015). A clinically driven TLR was
After the procedure, the patients were advised to
defined as treatment for recurrent angina pectoris
continue on aspirin (100 mg daily) for life unless
before the scheduled follow-up angiography. The
there were contraindications. Clopidogrel (75 mg
timing and diagnostic certainty of ST were assessed
daily) was also prescribed for at least 1 year after stent
according to the Academic Research Consortium
implantation.
definition (6).
Kan et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 11, 2016
JUNE 13, 2016:1115–23
The angiographic diagnosis of SF required an
independent analysis and the agreement of 2 inde-
Stent Fracture After DES
T A B L E 1 Baseline Clinical Characteristics of 6,555 Patients
pendent cardiologists (J.K., J.-J.Z.). Angiographic SF
using the stent boost technique was classified as
types IwIV according to Popma’s classification (5) as
shown in Figure 1. For suspected SF during surveil-
Male
Age, yrs
Hyperlipidemia
lance angiograms, IVUS or OCT was used. The prevalence of SF at the patient, vessel, and stent level
was calculated.
STATISTICAL ANALYSIS. The data are presented
Stent Fracture
(n ¼ 803)
Nonstent Fracture
(n ¼ 5,752)
603 (75.1)
4,279 (74.3)
0.635
64.6 10.1
64.1 10.3
0.205
p Value
536 (66.7)
3,828 (66.6)
0.936
Total cholesterol, mmol/l
4.27 1.09
4.21 1.09
0.143
LDL, mmol/l
0.004
2.74 0.94
2.63 0.93
Hypertension
593 (73.8)
4,269 (74.2)
0.830
Current smoker
291 (36.2)
2,094 (36.4)
0.938
Diabetes
291 (36.2)
1,928 (33.5)
0.130
151 (51.9)
934 (48.4)
0.068
0.108
as mean SD or median (interquartile range) and
Oral medicine
percentages. Categorical variables were compared
Insulin
between groups using the chi-square test or Fisher
Renal dysfunction
exact test as appropriate. Continuous variables were
Family history of CHD
402 (20.9)
1,143 (19.9)
11 (1.4)
29 (0.5)
0007
0.706
85 (10.6)
548 (9.5)
0.339
PVD
34 (4.2)
235 (4.1)
0.849
GI bleeding <3 months
13 (1.6)
83 (1.4)
0.640
Previous MI
104 (13.0)
536 (9.3)
0.002
was used for the clinical variables, lesion, procedural,
Previous PCI
85 (10.6)
650 (11.3)
0.591
and DES platform-based analysis of the risk factors for
Previous CABG
15 (1.9)
55 (1.0)
0.026
SF. The survival curve at the patient level was esti-
EF <40%
202 (25.2)
1,216 (21.1)
0.010
mated using the Kaplan–Meier method and was
Heart rate at rest, beats/min
74.2 11.1
73.9 11.9
0.519
433 (53.9)
3,234 (56.2)
compared between groups using Student unpaired
t test or the Mann-Whitney U test on the basis of the
distribution. Multivariable logistic regression analysis
compared using log-rank analysis. For calculation of
Stroke
69 (23.7)
164 (20.4)
Clinical presentation
0.526
Stable angina
the SF rate, the patients were grouped by individual
stents. The statistical analysis was performed using
SPSS 17.0 (SPSS Inc., Chicago, Illinois).
Unstable angina
108 (13.4)
786 (13.7)
AMI
262 (32.6)
1,732 (30.1)
NSTEMI
79 (9.8)
511 (8.9)
183 (22.8)
1,221 (21.2)
Considering the significant differences in the
STEMI
baseline clinical and lesion characteristics between
Medication
patients with and without SF, propensity score
Statin
138 (17.2)
1,016 (17.7)
0.767
matching (PSM) was used to compare adverse events
ACEI/ARB
207 (25.8)
1,376 (23.9)
0.253
Beta-blocker
130 (16.2)
920 (16.0)
0.878
Calcium-channel antagonist
242 (30.1)
1,662 (28.9)
0.481
39 (4.9)
235 (4.1)
0.301
at the end of the clinical follow-up between SF-based
groups to provide an unbiased estimation of treat-
Diuretic agents
ment effects. All clinical and angiographic variables
were included in the PSM analysis. The patients in the
SF group who had an estimated logit within 0.5
standard error of the selected patients in the non-SF
group were eligible for matching. If more than 1 pa-
Values are n (%) or mean SD.
ACEI ¼ angiotensin-converting enzyme inhibitor; AMI ¼ acute myocardial infarction;
ARB ¼ angiotensin receptor blocker; CABG ¼ coronary artery bypass graft; CHD ¼ coronary heart
disease; EF ¼ eject fraction; GI ¼ gastrointestinal; LDL ¼ low-density lipoprotein; MI ¼ myocardial
infarction; NSTEMI ¼ non–ST-segment elevation myocardial infarction; PCI ¼ percutaneous coronary
intervention; PVD ¼ peripheral vessel disease; STEMI ¼ ST-segment elevation myocardial infarction.
tient in the non-SF group met this criterion, we
randomly selected 1 patient for matching according to
nearest rule. Estimates of the adjusted differences in
risks are presented with 95% confidence intervals.
RESULTS
COMPARISON OF BASELINE CLINICAL VARIABLES
AT THE PATIENT LEVEL. Of the 6,555 patients, the
803 (12.3%) patients who experienced SF were more
likely to have high levels of serum LDL, a more
frequent family history of cardiovascular disease, a
history of prior myocardial infarction (MI)/coronary
artery bypass graft, and decreased left ventricular
function (Table 1).
in the right coronary artery (RCA). Vessels with
SF
had
more
complex
lesions,
as
defined
by
multiple-vessel disease, chronic total occlusion, and
ostial and bifurcation lesions and by more severe
tortuosity, angulation, and calcification. The treated
vessels in the SF group had smaller reference vessel
diameters and longer lesion lengths (Table 2).
Pre-dilation was performed in 73.0% of vessels
that experienced SF, which was significantly higher
than 59.7% in non-SF vessels (p < 0.001). Vessels with
SF were more likely to have smaller and longer stents
deployed at higher pressures (Table 3), leading to a
lower stent/vessel ratio. Overlapping stents were
VESSEL-LEVEL ANALYSIS OF ANGIOGRAPHIC AND
observed in 81.6% of SF vessels compared with
PROCEDURAL VARIABLES. More SFs were localized
34.4% of vessels in the non-SF group (p < 0.001).
1117
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Kan et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 11, 2016
JUNE 13, 2016:1115–23
Stent Fracture After DES
T A B L E 2 Angiographic Characteristics of 10,751 Diseased Vessels
Stent Fracture
(n ¼ 1,852)
Nonstent Fracture
(n ¼ 8,899)
T A B L E 3 Procedural Characteristics of 10,751 Diseased Vessels
p Value
Target lesion sites
Stent
Fracture
(n ¼ 1,852)
Nonstent
Fracture
(n ¼ 8,899)
p Value
586 (73.0)
3,433 (59.7)
<0.001
132 (7.1)
462 (5.2)
0.001
Pre-dilation
LAD
714 (38.6)
3,799 (42.7)
0.001
Stent for target lesion
LCX
122 (6.6)
1,833 (20.6)
<0.001
Stent number, n
1.96 0.61
1.44 0.68
<0.001
<0.001
Stent diameter, mm
2.84 0.44
3.09 0.47
<0.001
41.2 23.8
37.4 21.4
<0.001
11.9 2.3
11.6 2.2
1.01 0.29
1.09 0.38
<0.001
Left main
RCA
880 (47.5)
2,789 (31.3)
SVG
4 (0.2)
15 (0.2)
0.555
Stent length, mm
LIMA
0 (0)
1 (0.01)
1.000
Inflation pressure, atm
Stent/vessel ratio
Diseased vessels
1-vessel disease
494 (26.7)
2,688 (30.2)
<0.001
Multiple-vessel disease
1,358 (73.3)
6,211 (69.8)
0.003
2-vessel disease
569 (30.7)
3,077 (34.6)
0.002
3-vessel disease
789 (42.6)
3,134 (35.2)
<0.001
1.84 0.79
1.89 0.87
Treated lesion number
1–2
3
CTO
279 (65.5)
758 (25.4)
<0.001
Post-dilation
1,774 (95.8)
8,154 (91.6)
<0.001
3.31 0.49
3.33 0.52
0.153
11.6 2.9
11.4 2.8
0.002
Balloon diameter, mm
Balloon length, mm
Pressure, atm
18.9 3.7
15.3 3.6
<0.001
1.15 0.15
1.07 0.11
<0.001
1,552 (17.4)
Procedural time, min
44.8 17.5
27.9 83.1
<0.001
Contrast volume, ml
212.5 94.7
184.9 82.8
<0.001
1,321 (71.3)
7,132 (80.1)
<0.001
40 (2.2)
91 (1.0)
<0.001
0.024
<0.001
559 (30.2)
Overlapping
Balloon/stent ratio
Baseline TIMI flow grade
0
0.008
104 (5.6)
367 (4.1)
1,189 (64.2)
6,980 (78.4)
315 (17.0)
591 (6.6)
Complete revascularization
<0.001
TIMI flow grade <3
<0.001
Angiographic success
1,810 (97.7)
8,805 (98.9)
<0.001
In-lab complications
48 (2.6)
101 (1.1)
<0.001
15 (0.8)
39 (0.4)
0.047
0
7 (0.1)
0.612
6 (0.3)
17 (0.2)
0.267
Ostial lesion
271 (14.6)
593 (6.7)
Bifurcation lesions
738 (39.8)
3,566 (40.1)
0.875
Thrombus containing
244 (13.2)
1,085 (12.2)
0.244
No reflow
RVD <2.5 mm
243 (13.1)
562 (6.3)
<0.001
Acute closure
Lesion length >20 mm
934 (50.4)
1,891 (21.2)
<0.001
Distal embolization
Severe tortuosity
76 (4.1)
268 (3.0)
0.009
Perforation
19 (1.0)
33 (0.4)
0.001
Severe angulation
192 (10.4)
747 (8.4)
0.007
Dissection
54 (2.9)
90 (1.0)
<0.001
Severe calcification
69 (3.7)
246 (2.8)
0.026
SB ($2.0 mm) lost
24 (1.3)
60 (0.7)
0.006
RVD, mm
2.80 0.36
2.88 0.45
<0.001
Minimal lumen diameter, mm
1.87 0.25
1.90 0.34
0.119
67 11.2
66 12.7
0.586
37.6 16.3
32.2 10.9
Diameter stenosis, %
Lesion length, mm
Values are n (%) or mean SD.
SB ¼ side branch; TIMI ¼ Thrombolysis In Myocardial Infarction.
<0.001
Values are n (%) or mean SD.
CTO ¼ chronic total occlusion; LAD ¼ left anterior descending artery; LCX ¼ left circumflex
artery; LIMA ¼ left internal mammary artery; RCA ¼ right coronary artery; RVD ¼ reference vessel
diameter; SVG ¼ saphenous vein graft; TIMI ¼ Thrombolysis In Myocardial Infarction.
46.6%, and pattern III/IV was found in 53.4%. The
rate of SF within 1 year after a stenting procedure
was 31.2%; this rate was higher than the rate at
the 1- to 2-year follow-up (19.6%) but lower than
the rate after the 2-year follow-up (49.1%; all
SF vessels were more frequently treated with
p < 0.05).
post-dilation using larger noncompliant balloons
Of 3,630 fractured stents, 2,963 cases of SF were
(higher balloon/stent ratio) at higher inflation pres-
diagnosed by angiography and the stent boost tech-
sures, resulting in more edge dissections and loss of
nique, and the remaining 667 SF could not be deter-
side branches ($2.0 mm).
mined and were ultimately diagnosed by IVUS
INCIDENCE, PATTERNS, AND INDEPENDENT PREDICTORS
OF STENT FRACTURE. Of 10,751 diseased vessels and
16,482 implanted stents, the incidence of SF was
22.0% (n ¼ 3,630, Figure 2) at the stent level and
17.2% (n ¼ 1,852) at the vessel level. Variance of
%-SF between 4 centers was <3.7%, which could
be ignored. There was no significant difference in
(n ¼ 640) or OCT (n ¼ 27).
On the multivariate analysis, stents in the RCA,
stainless stents, stent length >25 mm, hinge motion,
overlapping, stent/vessel ratio <0.8 (requiring postdilation using a larger balloon at higher pressure),
and multiple stents were the 7 independent predictors of SF (Table 4).
and
CLINICAL CONSEQUENCE OF STENT FRACTURE.
female (16.8%; p ¼ 0.517) or between acute MI
The angiographic follow-up duration was 340 days
rate
of
SF
either
between
male
(17.4%)
(18.1%) and nonacute MI (16.8%; p ¼ 0.122, data
(SF group IQR: 36 to 33,905 days) and nonsignificant
not included in Table 3). The patterns of SF were
to 340 days (non-SF group range: from 35 to 3,395
distributed nearly equally; pattern I/II was found in
days; p ¼ 0.929) (Table 5).
Kan et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 11, 2016
JUNE 13, 2016:1115–23
Stent Fracture After DES
T A B L E 5 Clinical Follow-Up in 6,555 Patients
F I G U R E 2 Chronological Incidence and Patterns of SF
Time from PCI to angiographic
follow-up, days
SF
(n ¼ 803)
Without SF
(n ¼ 5,752)
341 (36–3,390)
340 (35–3,395)
1,528 (42.1)
1,221 (9.5)
In-stent restenosis*
Type I
1,154 (75.5)
927 (75.9)
Type II
163 (10.7)
98 (8.1)
Type III
25 (1.6)
27 (2.2)
Type IV
186 (12.2)
169 (1.9)
Days of clinical follow-up, days
1,805 (592–3,992) 1,724 (538–3,974)
2,243 (39.4)
Major adverse cardiac event
297 (37.0)
877 (15.2)
59 (7.3)
334 (5.8)
0.095
28 (3.5)
147 (2.6)
0.129
Cardiac death
0.073
<0.001
48 (6.0)
92 (1.6)
<0.001
Target lesion revascularization
193 (24.0)
356 (6.2)
<0.001
Target vessel revascularization
202 (25.2)
399 (6.9)
<0.001
211 (26.3)
492 (8.6)
<0.001
37 (4.6)
70 (1.2)
<0.001
Target lesion failure
(42.1%) SFs had ISR, with 5.1% having occlusion, 6.0%
0.069
369 (46.0)
Myocardial infarction
Of 3,630 fractured stents in 803 patients, 1,528
<0.001
Dual antiplatelet therapy
Death
fracture patterns.
0.923
<0.001
Patterns
Stent fracture (SF) increased over time with equal distribution of
p Value
Target vessel myocardial
infarction
44 (5.5)
73 (1.3)
<0.001
33 (4.1)
41 (0.7)
<0.001
Probable
11 (1.4)
32 (0.6)
0.016
Early
5 (0.6)
12 (0.2)
0.048
Stent thrombosis
having aneurysm and 4.6% having definite ST, and
Definite
TLR was required in 24.8% (n ¼ 379); all of these rates
were significantly different than the rates in stents
without fracture (10.7%, 0.3%, 0.7%, 1.03%, and 6.6%,
Late
11 (1.4)
11 (0.2)
<0.001
respectively; all p < 0.05) (Figure 3). Among fractured
Very late
26 (3.2)
50 (0.9)
<0.001
stents without ISR, the TLR rate after an additional
After Propensity Matching
median of 1,507 (276 to 3,502) days since the first
surveillance angiography was 0.8%; this rate was not
significantly different from the rate of 1.8% in
asymptomatic ISR induced by SF.
In general, patients (n ¼ 803) with any SF had
higher rates of MI, TLR, target vessel revascularization (TVR), definite/probable ST, and target vessel MI
leading to accumulative MACE and target lesion failure (TLF), rates 2 and 3 times as high as the rates in
Major adverse cardiac event
SF
(n ¼ 684)
Without SF
(n ¼ 684)
p Value
228 (33.3)
146 (21.3)
<0.001
Cardiac death
19 (2.8)
18 (2.6)
Myocardial infarction
31 (4.5)
14 (2.0)
0.014
Target lesion revascularization
152 (22.2)
65 (9.5)
<0.001
Target vessel revascularization
160 (23.4)
73 (10.7)
<0.001
162 (23.7)
81 (11.8)
<0.001
24 (3.5)
11 (1.6)
0.027
27 (3.9)
12 (1.8)
0.022
Target lesion failure
Target vessel myocardial infarction
Stent thrombosis
0.868
patients without SF (Table 5, Figure 4), respectively.
Definite
22 (3.2)
9 (1.3)
0.02
However, the rates of any-cause or cardiac death in
Probable
5 (0.7)
3 (0.4)
0.726
patients with SF did not differ from the rates in
Values are n (%) or median (interquartile range). *Stent-level analysis.
PCI ¼ percutaneous coronary intervention; SF ¼ stent fracture.
T A B L E 4 Independent Predictors of Stent Fracture
patients without SF. Most patients with SF were
Odds Ratio
95% Confidence
Interval
p Value
10.816
3.026–18.553
<0.001
By PSM, 684 pairs of patients were matched
Stainless stent
2.601
1.509–4.484
0.001
(Table 5). The results of the comparisons of MI, TLR,
0.006
TVR, target vessel MI, and definite ST between
RCA stent
Stent length >25 mm
2.444
1.130–5.010
Hinge motion
7.447
4.569–21.387
<0.001
Overlapping
4.037
1.814–8.060
0.001
Stent/vessel ratio <0.8*
5.289
1.155–6.284
<0.001
Multiple stents
5.224
3.839–7.108
<0.001
*Indicated the requirement of post-dilation using a larger balloon at higher
pressure.
LCX ¼ left circumflex artery; RCA ¼ right coronary artery.
asymptomatic (Table 5).
patients with versus without SF were as follows:
4.5% versus 2.0% (p ¼ 0.014), 22.2% versus 9.5%
(p < 0.001), 23.4% versus 10.7% (p < 0.001), 3.5%
versus 1.6% (p ¼ 0.027), and 3.2% versus 1.3%
(p ¼ 0.020), respectively. In unmatched patients with
SF group, the rate of cardiac death, MI, TLR, MACE,
and TLF was 7.6%, 14.3%, 34.5%, 59.7%, and 41.2%,
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Stent Fracture After DES
(for type III/IV ISR) was performed in 201 (53.3%)
F I G U R E 3 Complications Associated With SF
45.00%
stents, and balloon angioplasty (for type I/II ISR) was
performed in the remaining 178 (46.7%) stents; the
Stent fracture
42.10%
rates were similar to the rates (45.2% and 54.8%) in
Percentage (%)
40.00%
1,085 nonfractured stents that required TLR (non-SF-
35.00%
Without stent fracture
30.00%
TLR group) in 356 patients. After 1,523 (375 to 3,650)
24.80%
25.00%
days of follow-up, repeat ISR was detected in 23.8%
(n ¼ 90) stents, and 7.5% (n ¼ 7) required repeat
20.00%
15.00%
TLR; these results were not significantly different
10.70%
10.00%
6.60%
5.10%
compared with the results in the non-SF-TLR group
6.00%
5.00%
4.60%
(22.5% and 6.9%, respectively).
1.03%
0.70%
0.30%
0.00%
ISR
Occlusion
TLR
Aneurysm
Definite ST
DISCUSSION
A total of 42.1% of stent fractures (SF) had in-stent restenosis (ISR), and SF were
associated with more frequent target lesion revascularization (TLR), total occlusion,
The major findings of the present study on the basis
aneurysm formation, and definite stent thrombosis (ST) compared with stents without
of a larger patient population who underwent DES
fracture.
implantation are as follows: 1) the prevalence of SF at
the stent level was 22.0%, and the prevalence
increased over the 2-year follow-up; 2) given 6 inde-
extremely higher than those in unmatched patients
pendent predictors of SF (stents in the RCA, stainless
without SF (2.5%, 1.5%, 5.7%, 14.4%, and 8.1%,
stent, stent length >25 mm, hinge motion, over-
respectively; all p < 0.001) (derived from Table 5).
lapping, and multiple stents), stent/vessel ratio <0.8
CLINICAL OUTCOMES AFTER TREATING SF-RELATED
(requiring post-dilation using a larger balloon at
SYMPTOMATIC
that
higher pressure) were strongly correlated with SF;
required TLR in 193 patients, repeat DES implantation
3) SF was associated with significantly increased
ISR. Of
379
fractured
DES
Without stent fracture, 97.4%
Stent fracture, 96.5%
0.6
Log-Rank: p=0.126
0.4
0.2
A
0
0.6
Log-Rank: p<0.001
0.4
0.2
0.0
B
0
1.0
0.8
Without stent fracture, 93.8%
Stent fracture, 76.0%
0.6
Log-Rank: p<0.001
0.4
0.2
0.0
C
.00
1000
2000
3000
4000
Days after Stenting Procedure (d)
0.8
0.6
Without stent fracture, 93.1%
Stent fracture, 74.8%
Log-Rank: p<0.001
0.4
0.2
0.0
1000.00 2000.00 3000.00 4000.00
Days after Stenting Procedure (d)
D
.00
1000.00 2000.00 3000.00 4000.00
Days after Stenting Procedure (d)
1.0
1.0
Without stent fracture, 84.8%
Stent fracture, 63.0%
0.4
Log-Rank: p<0.001
0.2
E
.00 1000.00 2000.00 3000.00 4000.00
Days after Stenting Procedure (d)
0.8
Without stent fracture, 98.8%
Stent fracture, 95.4%
0.6
Log-Rank: p<0.001
0.4
0.2
0.0
F
0
1000
2000
3000
4000
Days after Stenting Procedure (d)
Survival Rate-free from Target
Lesion Failure (%)
0.6
1.0
Survival Rate-free from Stent
Thrombosis (%)
0.8
Survival Rate-free Target Vessel
Infarction (%)
Survival Rate-free from Major Adverse
Cardiac Event (%)
Without stent fracture, 98.4%
Stent fracture, 94.0%
1000
2000
3000
4000
Days after Stenting Procedure (d)
1.0
0.0
0.8
Survival Rate-free from Target Lesion
revascularization (%)
0.8
0.0
1.0
1.0
Survival Rate-free from Target vessel
Revascularization (%)
1.0
Survival Rate-free Myocardial
Infarction (%)
Survival Rate-free from Cardiac Death (%)
F I G U R E 4 Kaplan-Meier Survival Rate Between Patients With Versus Without Stent Fracture
0.8
Without stent fracture, 98.7%
Stent fracture, 94.5%
0.6
Log-Rank: p<0.001
0.4
0.2
0.0
G
0
0.8
0.6
2000
3000
Days after Stenting Procedure (d)
4000
Log-Rank: p<0.001
0.2
0.0
1000
Without stent fracture, 91.4%
Stent fracture, 73.7%
0.4
H
.00
1000.00 2000.00 3000.00 4000.00
Days after Stenting Procedure (d)
Stent fracture was associated with increased clinical events that did not translate into a higher rate of cardiac death compared with patients without stent fracture.
Kan et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 11, 2016
JUNE 13, 2016:1115–23
Stent Fracture After DES
angiographic (ISR, occlusion, and aneurysm forma-
However, the combination of a small stent and over
tion) and clinical (TLR, MI, ST, MACE, and TLF)
post-dilation at higher pressure could predict the
events after propensity score matching, which did not
occurrence of SF; this finding is similar but not
translate into significant differences in mortality
exactly the same as the finding of a previous study
among the 2 groups; and 4) balloon angioplasty for
(17) and suggests the importance of the selection of a
type I/II ISR and repeat implantation of DES for type
stent with an appropriate diameter.
III/IV ISR induced by SF had acceptable clinical
results.
Previous studies confirmed the correlation of SF
with ISR and subsequent events (7,15), in line with
The reported incidence of SF is dependent on
our findings. The majority of SFs were not silent. TLR
asymptomatic SF, different definitions and modalities
was required in 24.8% of stents with SF; these results
for SF, different percentages of surveillance angiog-
are similar to the results of studies by Lee et al. (19)
raphy, and longer follow-up durations, resulting in
and Chhatriwalla et al. (8). It has been suggested
much higher SF rates by autopsy than are clinically
that SF causes uneven and impaired local drug
reported (6,7). Theoretically, all pro-fracture factors
delivery at the stent site. However, in our analysis, SF
facilitate the process of metal fatigue over time (8–12);
mostly occurred long after drug delivery had been
metal fatigue is a mechanism leading to the postula-
terminated, indicating that ISR might have been
tion that more frequent SF might be detected over
caused by mechanical damage to a vessel wall rather
1-year follow-up, which is supported by our finding
than by the loss of drugs; this postulation is supported
that the SF rate after 2 years of follow-up reached
by the results of Halkin et al. (20). In our study,
49.1%. Furthermore, we found that patterns of SF
aneurysm was more common in patients with type III/
were almost equally distributed, and pattern II/III/IV
IV SF, which is in agreement with a previous study
SF more frequently lead to symptomatic ISR.
that reported that aneurysms were mostly observed in
Previous studies (13–18) have reported several
patients with complete SF. We found that asymp-
angiographic/procedural and clinical variables po-
tomatic ISR caused by SF had a lower rate of TLR,
werfully predicting the occurrence of SF. In general,
demonstrating the importance of severe chronological
RCA stents, stainless stents, longer stents or multiple
mechanical damage to vessels in inducing narrow
stents, and overlapping stents were universally
lumens in symptomatic patients. Because the base-
accepted to be correlated with SF (13–17). RCA stents,
line clinical and angiographic characteristics varied
particularly in the proximal-to-middle segment of the
widely, propensity score matching was used in our
RCA, were most commonly exposed to severe cardiac
analysis; in this analysis, SF remained associated with
motion and angulation, a mechanical mechanism
an increased rate of primary and secondary endpoints.
causing stent fracture (9,10). Once longer or multiple
From our results, the higher rate of MI, TLR, and ST in
or overlapping stents were used, aggressive post-
the SF group did not translate into significant differ-
dilation was usually performed to achieve optimal
ences in any-cause or cardiac mortality compared with
angiographic results (11–18), which was consistent
the non-SF group. Possible explanations for this
with our findings that patients with SF had more
finding might include the following: a) the small
frequent multivessel disease requiring multiple and
patient sample size underpowered the significance in
longer stents followed by post-dilation at a higher
death; and b) the percentage of dual antiplatelet
pressure. SF does not happen equally among different
therapy was relatively high, in accordance with the
stents, and more frequent SF was observed with
recommendation that for patients with SF and
stainless steel stents (7) compared with cobalt-
asymptomatic ISR, extending dual antiplatelet ther-
chromium platform stents (13), indicating less dura-
apy is recommended and appears safe (19).
bility with stainless stents, which should partially
Reintervention was associated with a significant
explain why cobalt-chromium stents are associated
reduction of MACE for patients with symptomatic SF-
with improvement of clinical outcomes (13,15–17). A
induced ISR (21), and this result was confirmed by this
recent study by Kuramitsu et al. (18) introduced the
study. The recommendation for reintervention for
concept of hinge motion, which together with over-
SF-induced ISR was that new generation DES (cobalt
lapping stent and tortuosity could predict the occur-
chromium platform) should be selected as the first
rence of SF; that concept is in line with our results.
line option; Ito et al. (22) and Ohya et al. (12) reported
The severe angulation, tortuosity, and hinge motion
significant increases in MACE, TLR, ST, and MI after
reflect
cardiac
implantation of a Cypher stent (Cordis, Johnson &
cycle, which puts stents under mechanical comprise.
Johnson, Fermont, California) for symptomatic SF-
The present study also found that small stents
induced ISR. A few studies have compared the ef-
(stent/vessel ratio <0.8) were not correlated with SF.
fect of restenting and ballooning with the recurrence
abnormal
movement
during
the
1121
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Kan et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 9, NO. 11, 2016
JUNE 13, 2016:1115–23
Stent Fracture After DES
of ISR (7). Our study showed acceptable results
frequently detected in anatomically complex lesions
after balloon angioplasty for focal ISR; these results
(angulation,
were in agreement with reports by Mitomo et al. (23).
understanding of abnormal distribution of the shear
tortuousity,
hinge
motion),
better
In that study, 50.4% of cases were treated with
stress (24) before and post-stenting underscores
ballooning.
the improvement of stenting techniques, which
should have been analyzed in further studies.
STUDY LIMITATIONS. Bare-metal stents and poor
quality of images were excluded from the current
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
analysis, and this exclusion could result in un-
Shao-Liang Chen, Nanjing First Hospital, Nanjing
derestimations of the SF rate. However, the high rate
Medical University, Nanjing, China 210006. E-mail:
of surveillance angiography in this study might
[email protected].
demonstrate the actual incidence of SF. Another limitation was the only use of Popma’s definitions of SF,
PERSPECTIVES
which might report the incidence of SF differently
compared with other definitions, and which may
result in a lower rate of SF than the true incidence,
even IVUS and OCT were used for some cases suspected to have SF. Finally, only a subset of patients
was included (always true in matching) and the potential influence of unmeasured confounders could
not be excluded.
WHAT IS KNOWN? SF is associated with increased
clinical events. However, the actual incidence of SF
varies from studies on the basis of different definitions.
WHAT IS NEW? We provide the actual rate of SF at
patient and vessel level after implantation of a DES
from a large patient population. The rate of cardiac
death, myocardial infarction, revascularization, and
stent thrombosis in SF patients was still significantly
CONCLUSIONS
different to the rate in non-SF patients after propen-
Given the factor that stent fracture is associated with
a higher rate of clinical events and that a stainless
stent is 1 of the independent factors of stent fracture,
more mechanical durable DES (cobalt chromium
platform stent) should replace first generation,
sity score matching.
WHAT IS NEXT? Further studies on mechanical
movement of heart and vascular fluid dynamic stress
are required to elucidate the mechanisms of SF.
stainless platform stents. As stent fracture is more
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KEY WORDS drug-eluting stent(s),
restenosis, stent fracture, stent thrombosis,
target lesion revascularization
1123