University of Groningen Antiplatelet therapy in myocardial infarction and coronary stent thrombosis Heestermans, Antonius Adrianus Cornelius Maria IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2010 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Heestermans, A. A. C. M. (2010). Antiplatelet therapy in myocardial infarction and coronary stent thrombosis. [s.n.]. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 09-09-2021
23
Embed
University of Groningen Antiplatelet therapy in myocardial ... · Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry J.W. van Werkum, A.A.C.M. Heestermans,
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
University of Groningen
Antiplatelet therapy in myocardial infarction and coronary stent thrombosisHeestermans, Antonius Adrianus Cornelius Maria
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.
Document VersionPublisher's PDF, also known as Version of record
Publication date:2010
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):Heestermans, A. A. C. M. (2010). Antiplatelet therapy in myocardial infarction and coronary stentthrombosis. [s.n.].
CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.
Non-culprit stenosis proximal of the stented segment which is left untreated (>50%)
14/437 (3.2) 8/866 (0.9) <0.0001
Total stent length – mm. 27.8 ± 15.2 23.7 ± 14.2 <0.0001Total number of stents 1.54 ± 0.82 1.34 ± 0.67 <0.0001Minimal stent diameter – mm. 3.0 ± 0.4 3.13 ± 0.4 <0.0001Maximal balloon pressure – atm. 13.7 ± 2.5 13.9 ± 2.5 0.1823Antithrombotic medication at the time of the index PCI
DM=diabetes mellitus ; MI=myocardial infarction; PCI=percutaneous coronary intervention; CABG=coronary artery bypass-grafting; CAD=coronary artery disease; PAD=peripheral artery disease; MDRDeGFR= Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate; LVEF=left ventricular ejection fraction; UAP=unstable angina pectoris; NSTEMI=non-ST elevated myocardial infarction; STEMI=ST-elevated myocardial infarction; LAD= left anterior descending artery; RCA=right coronary artery; RCX= right circumflex artery; TIMI-Thrombolysis in myocardial infarction.
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Chapter 9
142
Figure 1: Independent risk-factors for ST when comparing the total group of patients with ST
with all matched-controls.
Influence of the indication for the index PCI on ST rate and determinants of ST
With regard to the different indications for stent implantation, the cumulative incidence
of ST in patients who underwent an elective PCI for the indication stable angina pectoris
was low 113/11.207 patients (cumulative incidence:1.00%). However, the cumulative
incidence of ST was higher when the indication for index stent implantation was
unstable angina/NSTEMI (72/3960 patients, cumulative incidence: 1.8%) and for STEMI
(252/5842 cumulative incidence: 4.3%). Determinants of ST for the different indications
of index stent implantation are depicted in figure 2. Independent factors that predispose
to the development of ST in patients undergoing elective PCI with stent implantation for
the indication stable angina were undersizing, the presence of intermediate coronary
artery disease proximal to the culprit lesion, malignant disease, suboptimal procedural
result (TIMI flow post-PCI<3), LVEF<30%, uncovered dissection, multivessel disease,
LAD stenting and long total stent length. Predictors of ST in the setting of ACS (including
STEMI) as the indication for index PCI were undersizing, suboptimal procedural result
(TIMI flow post-PCI<3), uncovered dissection, the presence of intermediate coronary
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Coronary stent thrombosis
143
artery disease proximal to the culprit lesion, bifurcation lesion, any DES, no aspirin
therapy, LVEF<30%, the presence of intermediate coronary artery disease distal to the
culprit lesion and multivessel disease. Of note, peri-procedural use of glycoprotein (GP)
IIb/IIIa therapy for the indication ACS (including STEMI) was associated with a reduction
of ST. It is important to note that the time-varying covariable “cessation of clopidogrel”
was not included in these multivariate models.
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60
Total stent length (10mm)
LAD stenting
Multivessel disease
Dissection
LVEF <30%
TIMI flow post-PCI <3
Malignancy
50% proximal of culprit≥CAD
Undersizing 57.72
14.21
13.08
9.71
8.44
5.64
3.30
2.55
1.88
[6.26-223.9]
[3.82-52.87]
[1.99-85.93]
[1.84-50.0]
[2.21-32.17]
[1.88-16.94]
[1.30-8.40]
[1.07-6.09]
[1.18-2.50]
OR 95%-CI
P=0.0003
P<0.0001
P=0.0074
P=0.0073
P=0.0018
P=0.0021
P=0.0122
P=0.035
P=0.0042
P-value
Predictors of Stent thrombosisCases and matched controls with Stable Angina as indication for index PCI
>
>
OR0 4 8 12 16 20
GP IIb/IIIa therapy
Multivessel disease
50% distal of culprit≥CAD
LVEF <30
no ASA
Any DES
Bifurcation lesion
50% proximal of culprit≥CAD
Dissection
TIMI flow post-PCI <3
Undersizing 12.28
4.31
3.93
3.72
2.74
2.64
2.27
1.83
1.82
1.63
0.50
[4.72-31.93]
[2.24-8.33]
[2.06-7.48]
[2.14-6.47]
[1.81-4.16]
[1.63-4.29]
[1.09-4.74]
[1.14-2.95]
[1.14-2.90]
[1.04-2.56]
[0.33-0.75]
OR 95%-CI
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P=0.028
P=0.013
P=0.0117
P=0.033
P=0.001
P-value
Predictors of Stent thrombosisCases and matched controls with ACS as indication for index PCI
>
OR
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Chapter 9
144
Figure 2: Independent risk-factors for ST for the different indications of index stent
implantation (stable angina versus ACS)
Risk-factors for early ST (≤30 days) and late ST (>30 days)
Almost 75% of the STs occurred within 30 days after stent implantation. Figure 3 displays
the independent predictors of early ST (≤30 days after the index PCI) with associated
odds ratios (OR) and 95% CI and the independent predictors of late ST (>30 days after
the index PCI). Early predictors of ST included undersizing, uncovered dissection,
suboptimal procedural result (TIMI flow post-PCI<3), the presence of intermediate
coronary artery disease proximal to the culprit lesion, present malignant disease, no
aspirin, LVEF<30%, bifurcation lesion, the presence of intermediate coronary artery
disease distal to the culprit lesion, any DES, total number of stents. GP IIb/IIIa was
protective for the occurrence of early ST.
The following determinants were independently associated with the occurrence of late
ST: undersizing, present malignant disease, the presence of intermediate coronary
artery disease proximal to the culprit lesion, peripheral artery disease, diabetes mellitus,
bifurcation lesions, long total stent length and younger age.
Again, it is important to note that the time-varying covariable “cessation of clopidogrel”
was not included in these multivariate models.
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60
Total stent length (10mm)
LAD stenting
Multivessel disease
Dissection
LVEF <30%
TIMI flow post-PCI <3
Malignancy
50% proximal of culprit≥CAD
Undersizing 57.72
14.21
13.08
9.71
8.44
5.64
3.30
2.55
1.88
[6.26-223.9]
[3.82-52.87]
[1.99-85.93]
[1.84-50.0]
[2.21-32.17]
[1.88-16.94]
[1.30-8.40]
[1.07-6.09]
[1.18-2.50]
OR 95%-CI
P=0.0003
P<0.0001
P=0.0074
P=0.0073
P=0.0018
P=0.0021
P=0.0122
P=0.035
P=0.0042
P-value
Predictors of Stent thrombosisCases and matched controls with Stable Angina as indication for index PCI
>
>
OR0 4 8 12 16 20
GP IIb/IIIa therapy
Multivessel disease
50% distal of culprit≥CAD
LVEF <30
no ASA
Any DES
Bifurcation lesion
50% proximal of culprit≥CAD
Dissection
TIMI flow post-PCI <3
Undersizing 12.28
4.31
3.93
3.72
2.74
2.64
2.27
1.83
1.82
1.63
0.50
[4.72-31.93]
[2.24-8.33]
[2.06-7.48]
[2.14-6.47]
[1.81-4.16]
[1.63-4.29]
[1.09-4.74]
[1.14-2.95]
[1.14-2.90]
[1.04-2.56]
[0.33-0.75]
OR 95%-CI
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P=0.028
P=0.013
P=0.0117
P=0.033
P=0.001
P-value
Predictors of Stent thrombosisCases and matched controls with ACS as indication for index PCI
>
OR
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Coronary stent thrombosis
145
Figure 3: Independent risk-factors for early (≤30days) ST and late (>30 days) ST.
0 4 8 12 16 20
GP IIb/IIIa therapy
Total No of stents (per stent)
Any DES
50% distal of culprit≥CAD
Bifurcation
LVEF <30%
no ASA
Malignancy
50% proximal of culprit≥CAD
TIMI flow post-PCI
Dissection
Undersizing 13.46
6.19
5.24
4.15
3.06
2.82
2.71
2.42
2.22
[5.23-34.64]
[3.25-11.79]
[2.75-10.00]
[2.46-7.00]
[1.31-7.14]
[1.24-6.41]
[1.61-4.57]
[1.59-3.70]
[1.39-3.56]
OR 95%-CI
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P=0.0097
P=0.0132
P=0.0002
P<0.0001
P=0.0009
P-value
Predictors of Early (≤30 days) Stent thrombosis
>
2.07 [1.25-3.44] P=0.048
1.35 [1.04-1.76] P=0.0276
0.40 [0.25-0.65] P<0.0001
OR0 4 8 12 16 20 24 28 32
age (per 10 yrs)
Total stent length (per 10 mm)
Bifurcation
DM
PAD
50% proximal of culprit≥CAD
Malignancy
Undersizing 28.17
17.45
8.66
5.62
3.14
2.93
1.37
0.54
[4.73-163.90]
[4.67-65.26]
[3.18-23.56]
[1.43-22.09]
[1.33-7.45]
[1.37-6.23]
[1.04-1.79]
[0.39-0.76]
OR 95%-CI
P=0.0002
P<0.0001
P<0.0001
P=0.0133
P=0.0093
P=0.0005
P=0.0233
P=0.0004
P-value
Predictors of Late (>30 days) Stent thrombosis
>
>
OR
0 4 8 12 16 20
GP IIb/IIIa therapy
Total No of stents (per stent)
Any DES
50% distal of culprit≥CAD
Bifurcation
LVEF <30%
no ASA
Malignancy
50% proximal of culprit≥CAD
TIMI flow post-PCI
Dissection
Undersizing 13.46
6.19
5.24
4.15
3.06
2.82
2.71
2.42
2.22
[5.23-34.64]
[3.25-11.79]
[2.75-10.00]
[2.46-7.00]
[1.31-7.14]
[1.24-6.41]
[1.61-4.57]
[1.59-3.70]
[1.39-3.56]
OR 95%-CI
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P=0.0097
P=0.0132
P=0.0002
P<0.0001
P=0.0009
P-value
Predictors of Early (≤30 days) Stent thrombosis
>
2.07 [1.25-3.44] P=0.048
1.35 [1.04-1.76] P=0.0276
0.40 [0.25-0.65] P<0.0001
OR0 4 8 12 16 20 24 28 32
age (per 10 yrs)
Total stent length (per 10 mm)
Bifurcation
DM
PAD
50% proximal of culprit≥CAD
Malignancy
Undersizing 28.17
17.45
8.66
5.62
3.14
2.93
1.37
0.54
[4.73-163.90]
[4.67-65.26]
[3.18-23.56]
[1.43-22.09]
[1.33-7.45]
[1.37-6.23]
[1.04-1.79]
[0.39-0.76]
OR 95%-CI
P=0.0002
P<0.0001
P<0.0001
P=0.0133
P=0.0093
P=0.0005
P=0.0233
P=0.0004
P-value
Predictors of Late (>30 days) Stent thrombosis
>
>
OR
0 4 8 12 16 20
GP IIb/IIIa therapy
Total No of stents (per stent)
Any DES
50% distal of culprit≥CAD
Bifurcation
LVEF <30%
no ASA
Malignancy
50% proximal of culprit≥CAD
TIMI flow post-PCI
Dissection
Undersizing 13.46
6.19
5.24
4.15
3.06
2.82
2.71
2.42
2.22
[5.23-34.64]
[3.25-11.79]
[2.75-10.00]
[2.46-7.00]
[1.31-7.14]
[1.24-6.41]
[1.61-4.57]
[1.59-3.70]
[1.39-3.56]
OR 95%-CI
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P=0.0097
P=0.0132
P=0.0002
P<0.0001
P=0.0009
P-value
Predictors of Early (≤30 days) Stent thrombosis
>
2.07 [1.25-3.44] P=0.048
1.35 [1.04-1.76] P=0.0276
0.40 [0.25-0.65] P<0.0001
OR0 4 8 12 16 20 24 28 32
age (per 10 yrs)
Total stent length (per 10 mm)
Bifurcation
DM
PAD
50% proximal of culprit≥CAD
Malignancy
Undersizing 28.17
17.45
8.66
5.62
3.14
2.93
1.37
0.54
[4.73-163.90]
[4.67-65.26]
[3.18-23.56]
[1.43-22.09]
[1.33-7.45]
[1.37-6.23]
[1.04-1.79]
[0.39-0.76]
OR 95%-CI
P=0.0002
P<0.0001
P<0.0001
P=0.0133
P=0.0093
P=0.0005
P=0.0233
P=0.0004
P-value
Predictors of Late (>30 days) Stent thrombosis
>
>
OR
0 4 8 12 16 20
GP IIb/IIIa therapy
Total No of stents (per stent)
Any DES
50% distal of culprit≥CAD
Bifurcation
LVEF <30%
no ASA
Malignancy
50% proximal of culprit≥CAD
TIMI flow post-PCI
Dissection
Undersizing 13.46
6.19
5.24
4.15
3.06
2.82
2.71
2.42
2.22
[5.23-34.64]
[3.25-11.79]
[2.75-10.00]
[2.46-7.00]
[1.31-7.14]
[1.24-6.41]
[1.61-4.57]
[1.59-3.70]
[1.39-3.56]
OR 95%-CI
P<0.0001
P<0.0001
P<0.0001
P<0.0001
P=0.0097
P=0.0132
P=0.0002
P<0.0001
P=0.0009
P-value
Predictors of Early (≤30 days) Stent thrombosis
>
2.07 [1.25-3.44] P=0.048
1.35 [1.04-1.76] P=0.0276
0.40 [0.25-0.65] P<0.0001
OR0 4 8 12 16 20 24 28 32
age (per 10 yrs)
Total stent length (per 10 mm)
Bifurcation
DM
PAD
50% proximal of culprit≥CAD
Malignancy
Undersizing 28.17
17.45
8.66
5.62
3.14
2.93
1.37
0.54
[4.73-163.90]
[4.67-65.26]
[3.18-23.56]
[1.43-22.09]
[1.33-7.45]
[1.37-6.23]
[1.04-1.79]
[0.39-0.76]
OR 95%-CI
P=0.0002
P<0.0001
P<0.0001
P=0.0133
P=0.0093
P=0.0005
P=0.0233
P=0.0004
P-value
Predictors of Late (>30 days) Stent thrombosis
>
>
OR
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Chapter 9
146
The influence of antiplatelet therapy on the occurrence of ST
The proportion of cases and matched controls that were on clopidogrel therapy for the
time-frames of the different categories ST is presented in figure 4. In detail, a total of
134 (30.7%) cases were not on clopidogrel therapy at the time of the ST. Of these, in
9/140 (6.4%) patients presenting with an acute ST the clopidogrel was erroneously not
initiated, 30/179 (16.7%) patients with a subacute ST had discontinued the clopidogrel for
a median of 5 days [IQR: 3-7days], 39/58 (67.2%) patients with a late ST had discontinued
the clopidogrel for a median of 13 days [IQR: 7-61days] and 56/59 (94.9% ) patients
with a very late ST had discontinued the clopidogrel for a median of 200 days [IQR: 23-
981days].
After applying the exact elapsed time-frame between the index PCI and ST for every
case to their matched controls it is shown that a significant higher proportion of controls
were on clopidogrel therapy at the “virtual time” of occurrence of ST (figure 4). As
compared to patients on clopidogrel therapy, the lack of clopidogrel therapy at the time
of ST in the first 30 days after the index PCI was strongly associated with ST (HR 36.5,
95% CI: 8.0-167.8). Likewise, the lack of clopidogrel therapy at the time of ST between
30 days and 6 months after the index PCI was also linked to the occurrence of ST (HR
4.6, 95% CI: 1.4-15.3). Multivariate Cox proportional hazard analysis also found that
discontinuation of clopidogrel therapy after 6 months from the index stent implantation
was a predictor of ST (HR 5.9, 95% CI: 1.7-19.8).
Alternatively, given the fact that clopidogrel irreversibly inhibits the human platelet
throughout its entire lifespan (10-12 days), we hypothesized that cessation of
clopidogrel <14 days prior to the ST would reveal the temporal relationship between
the discontinuation of clopidogrel and ST. After introducing this time-varying co-variate
in the multivariate Cox proportional hazard model, “cessation of clopidogrel within 14
days prior to ST” in the first 30 days after the index PCI emerged as a highly significant
predictor of ST (HR 36.9, 95% CI: 7.9-173.3). Similarly, “cessation of clopidogrel within
14 days prior to ST” between 30 days and 6 months after the index PCI was also
independently associated with the occurrence of ST (HR 21, 95% CI: 2.2-198.3). The
number of events beyond the 6 months time-frame after stent implantation was too
small to reliably estimate the impact of “cessation of clopidogrel and the subsequent
occurrence of ST within 14 days” on the occurrence of ST in this subcategory of
patients.Another important finding relates to the magnitude of impact of “cessation
of clopidogrel and the subsequent occurrence of ST within 14 days” between DES and
BMS. The risk for stent thrombosis associated with “Cessation of clopidogrel and the
subsequent occurrence of ST within 14 days” was significantly higher in patients who
had received a DES as compared to those who had received a BMS (OR for DES: 1.88,
95%CI: 1.21-2.94, p=0.0052).
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Coronary stent thrombosis
147
Figure 4: Proportion of cases and their matched controls taking clopidogrel therapy according
to the elapsed time between stent implantation and the occurrence of ST.
A significant higher percentage of the patients with ST did not use aspirin therapy at the
time of the index as compared to their matched control (13.1% versus 4.5%, p<0.0001).
The predominant reasons for no aspirin treatment were coumadin use in 85/96 (84.4%)
patients and allergy to aspirin in 7/96 (7.3%) patients. Multivariate logistic regression
analysis identified that the absence of aspirin therapy was also strong independent
predictor of ST (HR 1.91 95% CI: 1.01-3.88, p=0.0487).
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Chapter 9
148
DISCUSSION
Given the devastating consequences of ST, great efforts should be directed to identify
those patients at highest risk, who would probably benefit most from an alternative
strategy. The findings of the present study add considerably to the understanding of the
profiles of patients at high risk for ST.
Although previous studies have already recognized multiple risk-factors that confer a
significant risk of ST [1-3, 5, 7, 10], many of these studies have limitations, mostly related
to an overall small sample size with a limited number of cases. Also, the identified
determinants of ST represent those that have been looked for and many theoretical
likely factors (such as present malignancy, severity of atherosclerotic disease, aspirin
use) are not investigated in most published studies.
The case-control design of our study as well as the acquisition of very detailed data
on medical history, medication use and angiographic characteristics enabled us to
comprehensively examine the most important risk-factors that are associated with
ST. Moreover, the large sample size allowed identification of relatively infrequent
determinants.
The highly variable duration of clopidogrel use throughout the years of patient
recruitment (2004-2007) allowed us to comprehensive study the impact of early
clopidogrel cessation after stent implantation. As expected, lack of clopidogrel therapy
at the time of the ST in the first 6 months after the index PCI was identified as the
strongest independent predictor of ST and this observation is in line with some [1, 2, 11)
but not all [3, 7] previous reports. Also, we predefined a likely “vulnerable time-frame”
between cessation of clopidogrel and the occurrence of ST (<14 days) and demonstrated
that this is the period that patients are at the highest risk for ST, especially when the
discontinuation of clopidogrel was within the first 6 months after stent implantation.
A novel and very important finding of the present study, contrary to a recently published
study [7], is the fact that the lack of clopidogrel therapy (but not necessarily cessation of
clopidogrel within the 14 days preceding the ST) beyond 6 months after index PCI was
a predictor of ST. A likely explanation for this difference may be the fact that previous
studies were hampered by a very low number of events (16 patients of whom 7 did
not use clopidogrel at time of ST) >6 months after coronary stent implantation [7].
Nonetheless, our results should also be interpreted with caution because only a small
portion of patients with ST beyond 6 months had discontinued the clopidogrel in the 14
days preceding the ST.
It remains pure speculative why “lack of clopidogrel therapy after 6 months from the
index stent implantation” but not “cessation of clopidogrel and the occurrence of ST
(<14 days)” beyond 6 months was a predictor of late and very late ST. Perhaps that the
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Coronary stent thrombosis
149
loss of protection by clopidogrel therapy rather than a “rebound in platelet reactivity”
may explain these findings.
Undersizing of the coronary stent was the second strongest predictor of ST in our
study. Indeed, previous studies have elucidated the importance of correct sizing
of coronary stents, in particular in patients with a high thrombotic burden with
subsequent vasoconstriction or severe and diffuse target vessel disease [12-16]. Despite
improvements in techniques and materials in the last decade, previous reports have
suggested that the incidence of incomplete stent deployment and undersizing ranges
from 20% to 30% and this percentage is even higher when assessed by intravascular
ultrasound [15, 17]. Notwithstanding the results of previous studies suggesting that the
judgment of the correct sizing and/or deployment of coronary stents is superior with the
use of IVUS [18], we demonstrated that the identification of undersizing of a coronary
stent by the simple means of eyeballing is a strong predictor of ST. In most of the cases,
undersizing was probably due to severe calcification or related to a high thrombotic
burden with subsequent vasoconstriction. However, also incorrect judgment of the true
coronary vessel size by the performing operator is a likely explanation for undersizing
in a considerable number of cases.
The long-term safety of DES has been a main topic of debate at recent international
cardiology meetings. In our study, patients who received a DES had higher baseline
risk-profiles and more complex lesion characteristics. Nonetheless, the use of a DES
was not independently associated with late or very late ST. In contrast, any DES use was
independently associated with ST in both the all cases versus all controls analysis as
well as in the sub analysis on risk-factors for early ST
Several previous studies have elucidated the importance of mechanical (both
angiographic and procedural factors) aetiologies underlying early ST [12, 15, 17].
Given the more complex lesion characteristics (an off-label DES indication) and limited
flexibility of the first generation of DES, uncovered endothelial damage during DES
implantation might explain this association between early ST and DES use.
Study limitations
Several limitations of the present study need to be acknowledged. First, notwithstanding
that a case-control design enables the evaluation of rare events such as ST, a case-
control design is at the same time vulnerable to several sorts of bias. Indeed, three
control patients were excluded from analysis because they were admitted for ST in
another non-participating hospital during follow-up. However, given the size of the
control group (2:1 ratio), the random selection of controls and the extent of differences in
clinical procedural and angiographic findings between cases and controls, it is unlikely
that the results would have changed considerably by increasing the number of controls.
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Chapter 9
150
Second, only angiographically documented cases with ST (“definite”) were reported.
This might have led to an underestimation of the actual incidence of ST because patients
who had suffered from a sudden cardiac death or from a silent stent occlusion were not
included in our analysis. Third, one may question our evaluation of the sizing of coronary
stents by simple means of eyeballing instead of using sophisticated techniques such as
IVUS or QCA. Nonetheless, visual estimation was able to detect undersizing in 18.1% of
the cases and in only 2.3% of the controls, which makes it a valuable tool.
Conclusion
We identified several important predictors of ST in the contemporary era of mixed
DES and BMS use. Discontinuation of clopidogrel, undersizing of the coronary stent,
presence of intermediate (>30%) coronary artery disease proximal to the culprit lesion
and concomitant malignant disease were the strongest predictors of ST. Risk-factors for
ST also vary throughout the different indications for PCI (stable angina versus ACS) and
differ for the different categories of ST (early vs late ST).
R1
R2
R3
R4
R5
R6
R7
R8
R9
R10
R11
R12
R13
R14
R15
R16
R17
R18
R19
R20
R21
R22
R23
R24
R25
R26
R27
R28
R29
R30
R31
R32
R33
R34
Coronary stent thrombosis
151
REFERENCE LIST
1. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126-30.
2. 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;113:1108-13.
3. 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;369:667-78.
4. Smit JJ, van ‘t Hof AW, de Boer MJ, et al. Incidence and predictors of subacute thrombosis in patients undergoing primary angioplasty for an acute myocardial infarction. Thromb Haemost 2006;96:190-5.
5. Rinaldi MJ, Kirtane AJ, Piana RN, et al. Clinical, procedural, and pharmacologic correlates of acute and subacute stent thrombosis: results of a multicenter case-control study with 145 thrombosis events. Am Heart J 2008;155:654-60.
6. Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006;48:2584-91.
7. 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;116:745-54.
8. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115:2344-51.
9. Huber MS, Mooney JF, Madison J, Mooney MR. Use of a morphologic classification to predict clinical outcome after dissection from coronary angioplasty. Am J Cardiol 1991;68:467-71.
10. Park DW, Park SW, Park KH, et al. Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol 2006;98:352-6.
11. 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;103:1967-71.
12. Moussa I, Di MC, Reimers B, Akiyama T, Tobis J, Colombo A. Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome. J Am Coll Cardiol 1997;29:6-12.
13. Takano Y, Yeatman LA, Higgins JR, et al. Optimizing stent expansion with new stent delivery systems. J Am Coll Cardiol 2001;38:1622-7.
14. Brodie BR, Cooper C, Jones M, Fitzgerald P, Cummins F. Is adjunctive balloon postdilatation necessary after coronary stent deployment? Final results from the POSTIT trial. Catheter Cardiovasc Interv 2003;59:184-92.
15. Cheneau E, Leborgne L, Mintz GS, et al. Predictors of subacute stent thrombosis: results of a systematic intravascular ultrasound study. Circulation 2003;108:43-7.
16. Cheneau E, Satler LF, Escolar E, et al. Underexpansion of sirolimus-eluting stents: incidence and relationship to delivery pressure. Catheter Cardiovasc Interv 2005;65:222-6.
17. Uren NG, Schwarzacher SP, Metz JA, et al. Predictors and outcomes of stent thrombosis: an intravascular ultrasound registry. Eur Heart J 2002;23:124-32.
18. Briguori C, Tobis J, Nishida T, et al. Discrepancy between angiography and intravascular ultrasound when analysing small coronary arteries. Eur Heart J 2002;23:247-54.