Abstract
Background:
Stent fracture (SF) and peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation are considered to be related to very late stent thrombosis (VLST). How dual antiplatelet therapy (DAPT) beyond 1 year affects the clinical outcomes of patients with SF or PSS remains unclear.
Methods and Results:
Based on their DAPT status, 1,962 patients undergoing SES implantation were classified as on-thienopyridine (n=1,404) or off-thienopyridine (n=558). The 6-year incidence of VLST was significantly lower in the on-thienopyridine patients (0.56% vs. 1.8%, P=0.01), whereas cardiac death and myocardial infarction (MI) were similar (5.0% vs. 6.2%, P=0.31; 3.2% vs. 4.0%, P=0.33; respectively). The 1,962 patients were also classified as having SF/PSS (n=256) or non-SF/PSS (n=1,706). In the SF/PSS group, VLST and MI were significantly lower in on-thienopyridine patients (1.9% vs. 10.1%, P=0.003; 3.5% vs. 10.3%, P=0.02; respectively). In the non-SF/PSS group, VLST and MI were similar (0.36% vs. 0.45%, P=0.78; 3.2% vs. 3.0%, P=0.93; respectively). In both groups, cardiac death was similar (3.6% vs. 4.3%, P=0.78; 5.2% vs. 6.5%, P=0.32; respectively).
Conclusions:
Prolonged DAPT was associated with significantly lower incidences of VLST and MI in the SF/PSS group, but had no effect on cardiac death, VLST, or MI in the non-SF/PSS group.
The optimal duration of dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents (DES) still remains a matter of debate. Current guidelines recommend 6-month DAPT for patients after elective DES implantation.1,2
However, a short period of DAPT does not seem to be always adequate for all patients, according to 2 recent large randomized trials showing that prolonged DAPT significantly reduced the risk of atherothrombotic events.3,4
Thus, developing a personalized medication strategy with optimal DAPT duration is increasingly important. The balance between the risk of atherothrombotic events and that of bleeding complications needs to be evaluated by using a prediction model such as the DAPT score.5
With regards to patients treated with first-generation DES, they have worse safety profiles with higher rates of stent thrombosis than those treated with second-generation DES.6,7
Jensen et al have reported that the incidence of major adverse cardiovascular events was significantly higher in patients after sirolimus-eluting stent (SES) implantation than in those after everolimus-eluting stents implantation, largely because of a higher risk of definite very late stent thrombosis (VLST).8
We have reported that stent fracture (SF) or peri-stent contrast staining (PSS) after SES implantation is associated with VLST.9,10
However, the effect of prolonged DAPT on the clinical outcomes of patients with SF or PSS after SES implantation remains unknown. Therefore, we sought to elucidate the effect of DAPT beyond 1 year on clinical outcomes in patients with SF or PSS after SES implantation.
Methods
We identified consecutive patients undergoing first-time SES (CypherTM) implantation between November 2002 and October 2007 and subsequent follow-up angiography within 12 months. First, the relationship between the continuation of thienopyridine therapy and clinical outcomes including all-cause death, cardiac death, bleeding-related death, myocardial infarction (MI), and definite VLST with a landmark analysis at 1 year after SES implantation was examined. Moreover, SF and PSS were evaluated by follow-up angiography within 1 year, and patients with SF, PSS, or both were classified as the SF/PSS group and those with neither SF nor PSS as the non-SF/PSS group. The effect of thienopyridine therapy beyond 1 year on clinical events was assessed between these groups.
The data on the discontinuation of thienopyridine therapy at 1 year after the index procedure were collected retrospectively. The continuation of thienopyridine therapy was defined as uninterrupted administration of a thienopyridine (75 mg of clopidogrel sulfate or 200 mg of ticlopidine hydrochloride daily) within 1 year. Transient withdrawal that lasted at least 1 month was classified as discontinuation of thienopyridine therapy. The recommended DAPT regimen was aspirin (≥81 mg daily) indefinitely and a thienopyridine for at least 3 months. The duration of thienopyridine therapy was left to the discretion of each attending physician. Follow-up information including clinical events and prescription of antiplatelet therapy was collected from hospital charts or by contacting patients or their referring physicians.
Follow-up coronary angiography (CAG) at 8 and 20 months was scheduled after the index procedure according to the local protocol. Patients without follow-up CAG at 8 months after the index procedure were excluded but patients without follow-up CAG at 20 months after the index procedure were not. SF was defined as the complete separation of stent segments or stent struts confirmed by follow-up CAG and evaluated through multiple projections.9
Moreover, focus images, inverse images, and images without the use of catheter or contrast media were used to detect SF, especially in non-restenotic lesions (Figure S1). PSS was defined as vessel enlargement with contrast medium staining outside the stent for >20% of the stent diameter measured by quantitative CAG.9
SF, PSS, or both were diagnosed by consensus of 2 experienced interventional cardiologists (Y.F. and K.K.). MI was defined as a new Q wave >0.04 s or elevation of serum creatine kinase levels to greater than 3-fold the upper limit of normal values with an elevated myocardial band fraction. VLST was defined as definite stent thrombosis according to the Academic Research Consortium definition. Bleeding-related death was defined as directly caused by bleeding with no other cause, as indicated as Bleeding Academic Research Consortium definition type 5a or 5b.11
Statistical Analysis
Statistical analysis was performed with the aid of commercially available software (IBM SPSS Statistics 23, Armonk, NY, USA). Data are expressed as mean±standard deviation or median and interquartile range for continuous variables and as numbers and percentages for categorical variables. Continuous variables were compared between groups using Student’s t-test or the Wilcoxon rank-sum test, based on the distribution. Categorical variables were compared between groups with the χ2
test or Fisher’s exact test, as appropriate. Estimation of the cumulative event rate was performed by the Kaplan-Meier method and differences were assessed with the log-rank test. A 2-sided P-value <0.05 was regarded as statistically significant.
Results
Of 2,394 patients undergoing their first SES implantation between November 2002 and October 2007, 432 were excluded because of no angiographic follow-up within 1 year. Of the resultant 1,962 patients, clinical outcomes were compared between 1,404 patients continuing thienopyridine therapy and 558 patients discontinuing thienopyridine therapy. Baseline characteristics are shown in
Table 1. Patients continuing thienopyridine therapy were significantly younger and more likely to be male, and to have diabetes mellitus, dyslipidemia, acute coronary syndrome, and low ejection fraction. Complete follow-up data were available in 96.7% of the patients at 6 years after SES implantation. During the 6-year follow-up period, definite VLST developed in 16 patients (0.82% [0.16% per year]), and the incidence of definite VLST was significantly lower in patients continuing thienopyridine therapy beyond 1 year than in those discontinuing thienopyridine therapy within 1 year (0.56% vs. 1.8%, P=0.01) (Figure 1). The incidence of stent thrombosis-related MI was also significantly lower in patients continuing thienopyridine therapy than in those discontinuing thienopyridine therapy (0.4% vs. 1.8%, P=0.003). However, the rate of spontaneous MI was comparable between the 2 therapy groups (2.8% vs. 2.3%, P=0.58). Moreover, the rates of cardiac death and bleeding-related death did not differ significantly between patients continuing or discontinuing thienopyridine therapy (5.0% vs. 6.2%, P=0.31 and 1.9% vs. 1.2%, P=0.27, respectively) (Table 2).
Table 1.
Characteristics of On-Thienopyridine and Off-Thienopyridine Patients After SES Implantation
| |
On-thienopyridine
(n=1,404) |
Off-thienopyridine
(n=558) |
P value |
| Age, years |
67.8±10.5 |
69.6±10.5 |
0.001 |
| ≤60 |
344 (24.5) |
115 (20.6) |
0.07 |
| Male, n (%) |
1, 076 (76.6) |
399 (71.5) |
0.02 |
| Hypertension, n (%) |
987 (70.3) |
404 (72.4) |
0.38 |
| Diabetes mellitus, n (%) |
492 (35.0) |
159 (28.5) |
0.006 |
| Insulin-treated, n (%) |
176 (12.5) |
44 (7.9) |
0.003 |
| Dyslipidemia, n (%) |
563 (40.1) |
183 (32.8) |
0.003 |
| PAD, n (%) |
80 (5.7) |
32 (5.7) |
1.0 |
| Previous stroke, n (%) |
145 (10.3) |
53 (9.5) |
0.62 |
| Previous MI, n (%) |
581 (41.4) |
228 (40.9) |
0.84 |
| Previous CABG, n (%) |
100 (7.1) |
27 (4.8) |
0.07 |
| Previous PCI, n (%) |
636 (45.3) |
245 (43.9) |
0.58 |
| ACS, n (%) |
247 (17.6) |
71 (12.7) |
0.008 |
| LVEF, % |
55.1±10.6 |
56.5±10.7 |
0.01 |
| ≤40%, n (%) |
147 (10.7) |
53 (9.8) |
0.56 |
| eGFR, mL/min/1.73 m2 |
60.1±22.1 |
58.8±20.0 |
0.20 |
| CKD stage 4 or 5, n (%) |
109 (7.8) |
45 (8.1) |
0.85 |
| Hemodialysis, n (%) |
48 (3.4) |
18 (3.2) |
0.89 |
| Angiographic disease extent, n (%) |
|
|
0.29 |
| 1-vessel |
694 (49.4) |
302 (54.1) |
|
| 2-vessel |
392 (27.9) |
146 (26.2) |
|
| 3-vessel |
187 (13.3) |
65 (11.6) |
|
| LMT disease |
131 (9.3) |
45 (8.1) |
|
Data are mean±SD when appropriate. ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; LMT, left main trunk; LVEF, left ventricular ejection fraction; MI, myocardial infarction; On-thienopyridine, patients continuing thienopyridine therapy beyond 1 year; Off-thienopyridine, patients discontinuing thienopyridine therapy within 1 year; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; SES, sirolimus-eluting stent.
Table 2.
6-Year Clinical Outcomes of On-Thienopyridine and Off-Thienopyridine Patients After SES Implantation
| |
On-thienopyridine
(n=1,404) |
Off-thienopyridine
(n=558) |
Log-rank
P value |
| All-cause death, n (%) |
234 (16.8) |
109 (19.7) |
0.16 |
| Cardiac, n (%) |
65 (5.0) |
32 (6.2) |
0.31 |
| Noncardiac, n (%) |
159 (11.7) |
70 (13.1) |
0.45 |
| Bleeding-related, n (%) |
25 (1.9) |
6 (1.2) |
0.27 |
| Unknown, n (%) |
10 (0.8) |
7 (1.4) |
0.24 |
| MI, n (%) |
38 (3.2) |
20 (4.0) |
0.33 |
| Spontaneous, n (%) |
33 (2.8) |
11 (2.3) |
0.58 |
| Stent thrombosis-related, n (%) |
5 (0.4) |
9 (1.8) |
0.003 |
Abbreviations as in Table 1.
Table 3
shows the profiles of the patients in the cases of VLST. Of the 16 patients with definite VLST, 10 belonged to the SF/PSS group and 6 belonged to the non-SF/PSS group. In the SF/PSS group, 7 patients discontinued thienopyridine therapy within 1 year and all 10 patients were discontinuing DAPT at the onset of VLST. All 10 VLST cases including the presence of SF and PSS at 8-month follow-up CAG had SF and PSS when VLST occurred.
Table 3.
Profiles of Patient With VLST
Case
no. |
Age,
years |
Sex |
Target lesion |
Thienopyridine
at 1 year |
Time from PCI to
VLST, months |
Therapy at the onset of VLST |
SF |
PSS |
| Aspirin |
Thienopyridine |
| 1 |
64 |
M |
RCA distal |
On |
36 |
On |
Off |
− |
+ |
| 2 |
50 |
M |
LAD mid |
On |
57 |
On |
Off |
+ |
− |
| 3 |
68 |
F |
RCA mid |
On |
70 |
Off |
On |
+ |
− |
| 4 |
44 |
M |
RCA proximal |
Off |
16 |
Off |
Off |
+ |
+ |
| 5 |
66 |
M |
RCA proximal |
Off |
33 |
On |
Off |
+ |
− |
| 6 |
60 |
M |
LAD mid |
Off |
34 |
On |
Off |
+ |
+ |
| 7 |
64 |
F |
LAD proximal |
Off |
37 |
Off |
Off |
+ |
+ |
| 8 |
87 |
M |
LAD proximal |
Off |
41 |
On |
Off |
+ |
+ |
| 9 |
52 |
F |
LAD mid |
Off |
55 |
On |
Off |
− |
+ |
| 10 |
38 |
M |
LAD proximal |
Off |
57 |
On |
Off |
+ |
− |
| 11 |
76 |
M |
LAD proximal |
On |
21 |
On |
Off |
− |
− |
| 12 |
79 |
M |
SVG |
On |
27 |
On |
On |
− |
− |
| 13 |
60 |
F |
RCA proximal |
On |
51 |
On |
On |
− |
− |
| 14 |
79 |
F |
LAD proximal |
On |
58 |
Off |
Off |
− |
− |
| 15 |
71 |
M |
LAD mid |
Off |
25 |
On |
Off |
− |
− |
| 16 |
66 |
M |
LAD proximal |
Off |
41 |
Off |
Off |
− |
− |
LAD, left anterior descending artery; PCI, percutaneous coronary intervention; PSS, peri-stent contrast staining; RCA, right coronary artery; SF, stent fracture; SVG, saphenous vein graft; VLST, very late stent thrombosis.
Follow-up CAG within 1 year detected SF in 228 patients (11.6%), PSS in 67 patients (3.4%), and SF/PSS group in 256 patients (13.0%). Of the 1,962 patients, the 256 were classified as the SF/PSS group and the remaining 1,706 as the non-SF/PSS group. The follow-up rate for each group is shown in
Figure 2.
Characteristics of the SF/PSS and non-SF/PSS groups are shown in
Table 4. In the SF/PSS group, patients continuing thienopyridine therapy were more likely to be male and have severe coronary artery disease, such as left main trunk or 3-vessel disease. In the non-SF/PSS group, patients continuing thienopyridine therapy were significantly younger and more likely to have diabetes mellitus, dyslipidemia, acute coronary syndrome, and low ejection fraction.
Table 4.
Characteristics of the SF/PSS and Non-SF/PSS Groups
| |
SF/PSS group |
Non-SF/PSS group |
On-thienopyridine
(n=181) |
Off-thienopyridine
(n=75) |
P value |
On-thienopyridine
(n=1,223) |
Off-thienopyridine
(n=483) |
P value |
| Age, years |
66.8±11.7 |
69.0±11.0 |
0.18 |
68.0±10.3 |
69.7±10.5 |
0.002 |
| ≤60 |
49 (27.1) |
17 (22.7) |
0.46 |
295 (24.1) |
98 (20.3) |
0.09 |
| Male, n (%) |
141 (77.9) |
48 (64.0) |
0.02 |
935 (76.5) |
351 (72.7) |
0.10 |
| Hypertension, n (%) |
132 (72.9) |
57 (76.0) |
0.61 |
855 (69.9) |
347 (71.8) |
0.43 |
| Diabetes mellitus, n (%) |
61 (33.7) |
24 (32.0) |
0.79 |
431 (35.2) |
135 (28.0) |
0.004 |
| Insulin-treated, n (%) |
22 (12.2) |
5 (6.7) |
0.26 |
154 (12.6) |
39 (8.1) |
0.008 |
| Dyslipidemia, n (%) |
75 (41.4) |
33 (44.4) |
0.71 |
488 (39.9) |
150 (31.1) |
0.001 |
| PAD, n (%) |
11 (6.1) |
4 (5.3) |
1.0 |
69 (5.6) |
28 (5.8) |
0.90 |
| Previous stroke, n (%) |
17 (9.4) |
5 (6.7) |
0.63 |
128 (10.5) |
48 (9.9) |
0.75 |
| Previous MI, n (%) |
82 (45.3) |
34 (45.3) |
1.0 |
499 (40.8) |
194 (40.2) |
0.81 |
| Previous CABG, n (%) |
21 (11.6) |
5 (6.7) |
0.27 |
79 (6.5) |
22 (4.6) |
0.13 |
| Previous PCI, n (%) |
80 (44.2) |
28 (37.3) |
0.31 |
556 (45.5) |
217 (44.9) |
0.84 |
| ACS, n (%) |
33 (18.2) |
8 (10.7) |
0.13 |
214 (17.5) |
63 (13.0) |
0.03 |
| LVEF, % |
54.0±11.4 |
54.9±13.0 |
0.60 |
55.3±10.4 |
56.7±10.3 |
0.01 |
| ≤40%, n (%) |
25 (13.8) |
9 (12.0) |
0.74 |
122 (10.1) |
44 (9.1) |
0.58 |
| eGFR, mL/min/1.73 m2 |
61.6±23.8 |
58.8±19.5 |
0.36 |
59.9±21.9 |
58.8±20.1 |
0.34 |
| CKD stage 4 or 5, n (%) |
12 (6.6) |
5 (6.7) |
1.0 |
97 (7.9) |
40 (8.3) |
0.81 |
| Hemodialysis, n (%) |
5 (2.8) |
2 (2.7) |
1.0 |
43 (3.5) |
16 (3.3) |
0.84 |
| Angiographic disease extent, n (%) |
|
|
0.02 |
|
|
0.58 |
| 1-vessel |
68 (37.6) |
38 (50.7) |
|
626 (51.2) |
264 (54.7) |
|
| 2-vessel |
55 (30.4) |
27 (36.0) |
|
337 (27.6) |
119 (24.6) |
|
| 3-vessel |
41 (22.7) |
8 (10.7) |
|
146 (11.9) |
57 (11.8) |
|
| LMT disease |
17 (9.4) |
2 (2.7) |
|
114 (9.3) |
43 (8.9) |
|
Data are mean±SD when appropriate. Abbreviations as in Table 1.
The incidence of VLST in the SF/PSS group was significantly lower in patients continuing thienopyridine therapy beyond 1 year than in those discontinuing thienopyridine therapy within 1 year (1.9% vs. 10.1%, P=0.003). In contrast, the incidence of VLST in the non-SF/PSS group was comparable between patients continuing or discontinuing thienopyridine therapy (0.36% vs. 0.45%, P=0.78) (Figure 3A,B). Furthermore, in the SF/PSS group, all 7 cases of MI in patients discontinuing thienopyridine therapy were related to VLST, and the rate of MI was significantly lower in patients continuing thienopyridine therapy than in those discontinuing thienopyridine therapy (3.5% vs. 10.3%, P=0.02); however, the incidence of cardiac death was similar (3.6% vs. 4.3%, P=0.78). On the other hand, in the non-SF/PSS group, the rates of cardiac death and MI were comparable between patients continuing and discontinuing thienopyridine therapy (5.2% vs. 6.5%, P=0.32 and 3.2% vs. 3.0%, P=0.93, respectively). The rates of bleeding-related death were not significantly different between patients continuing or discontinuing thienopyridine therapy in both the SF/PSS and non-SF/PSS groups (0% vs. 1.6%, P=0.12 and 2.2% vs. 1.2%, P=0.16, respectively) (Table 5).
Table 5.
6-Year Clinical Outcomes of the SF/PSS and Non-SF/PSS Groups
| |
SF/PSS group (n=256) |
Non-SF/PSS group (n=1,706) |
On-thienopyridine
(n=181) |
Off-thienopyridine
(n=75) |
Log-rank
P value |
On-thienopyridine
(n=1,223) |
Off-thienopyridine
(n=483) |
Log-rank
P value |
| All-cause death, n (%) |
27 (15.0) |
15 (20.2) |
0.35 |
207 (17.1) |
94 (19.6) |
0.25 |
| Cardiac, n (%) |
6 (3.6) |
3 (4.3) |
0.78 |
59 (5.2) |
29 (6.5) |
0.32 |
| Noncardiac, n (%) |
18 (10.2) |
12 (16.7) |
0.19 |
141 (11.9) |
58 (12.6) |
0.77 |
| Bleeding-related, n (%) |
0 (0.0) |
1 (1.6) |
0.12 |
25 (2.2) |
5 (1.2) |
0.16 |
| Unknown, n (%) |
3 (1.8) |
0 (0.0) |
0.27 |
7 (0.7) |
7 (1.7) |
0.07 |
| MI, n (%) |
5 (3.5) |
7 (10.3) |
0.02 |
33 (3.2) |
13 (3.0) |
0.93 |
| Spontaneous, n (%) |
2 (1.4) |
0 (0.0) |
0.39 |
31 (3.0) |
11 (2.6) |
0.71 |
| Stent thrombosis-related, n (%) |
3 (2.1) |
7 (10.3) |
0.007 |
2 (0.2) |
2 (0.4) |
0.34 |
Abbreviations as in Tables 1,3.
Discussion
The principal findings of this study are as follows. (1) In all the study patients undergoing their first-time SES implantation, the rate of definite VLST was significantly lower in patients continuing thienopyridine therapy beyond 1 year than in those discontinuing thienopyridine therapy within 1 year, whereas the rates of MI and cardiac death were comparable between groups. (2) In the SF/PSS group, the rates of definite VLST and MI were significantly lower in patients continuing thienopyridine therapy beyond 1 year than in those discontinuing thienopyridine therapy within 1 year, whereas the rate of cardiac death was comparable between groups. (3) In the non-SF/PSS group, the rates of definite VLST, MI, and cardiac death were comparable between patients continuing or discontinuing thienopyridine therapy.
The current study demonstrated that prolonged thienopyridine therapy was associated with a significantly lower VLST rate in the study population undergoing SES implantation. A substudy from the PROTECT study reported a strong interaction between DES type and DAPT use, which affected the incidence of stent thrombosis, and that VLST events with SES were related to DAPT discontinuation.12
Those results are consistent with ours. Moreover, our data demonstrated that prolonged thienopyridine therapy was associated with a significantly lower rate of stent thrombosis-related MI, but was not associated with the total rate of MI. Data on the benefit of prolonged DAPT for secondary prevention of MI are inconsistent. The DAPT study showed that prolonged DAPT reduced the incidence of both stent-related and non-stent-related MI.3
On the other hand, the DES LATE study demonstrated that prolonged DAPT did not reduce MI.13
Therefore, the efficacy of prolonged DAPT for secondary prevention of coronary thrombotic events might depend on the risk of coronary events in the study population.
Identifying those patients who will benefit from prolonged DAPT has great clinical importance. In the SF/PSS group, prolonged thienopyridine therapy was associated with a significantly lower VLST rate. Our previous reports demonstrated that SF or PSS after SES implantation has a close association with VLST.9,10
Moreover, thrombosis at sites of SF or PSS was observed in a pathologic analysis14
and by optical coherence tomography.15
In this present study, we reported 16 cases of definite VLST. It is intriguing that all 10 patients who had angiographic SF or PSS were discontinuing DAPT when VLST occurred. Although the exact relationship between SF or PSS and subsequent VLST remains unclarified, SF or PSS is considered to be a morphological substrate of VLST, and DAPT cessation seems to play an important role in developing VLST in the presence of SF or PSS. Thus, these findings underscore the significance of DAPT continuation to prevent the development of VLST in patients who have SF or PSS after SES implantation. On the other hand, prolonged thienopyridine therapy was not associated with a lower incidence of cardiac death in patients with SF or PSS. Although the reason is unclear, it might be attributed to the fact that VLST affects the mortality rate less than early or late stent thrombosis.16–18
Also, there could be a possibility that VLST includes more restenosis-related stent thrombosis than early or late stent thrombosis, which might result in a decrease in cardiac deaths with VLST because of the development of collateral arteries. In contrast, no significant differences in the rates of VLST, MI or cardiac death were observed between patients continuing or discontinuing thienopyridine therapy in the non-SF/PSS group. Therefore, discontinuation of thienopyridine therapy within 1 year could be an acceptable strategy in patients with neither SF nor PSS.
The association between SF or PSS and clinical events has been reported in patients treated with newer-generation DES.19–21
We also reported that definite VLST was observed in 1 patient, in which PSS was identified at follow-up CAG and that patient had discontinued all antiplatelet drugs before the onset of VLST.22
However, we cannot evaluate the efficacy of prolonged DAPT for patients with SF and/or PSS after everolimus-eluting stents implantation because the rate of VLST was too low.
SES have become a thing of the past, but millions of patients were treated with them, and we encounter patients who have SF or PSS at a small but constant rate in real-world clinical practice. Therefore, we consider that our current findings have important implications for deciding the optimal duration of thienopyridine therapy in patients who have a SES.
Study Limitations
First, this is a single-center retrospective study with a long follow-up period and a high follow-up rate, including a relatively large number of patients. The incidence of VLST was low, and definite VLST developed in only 16 patients, which may be underpowered to show a statistically significant difference. Second, all of the study population underwent follow-up CAG because PSS and SF in our study were detected by follow-up CAG; thus, a selection bias exists. Third, the current analysis was retrospective, and the duration of thienopyridine therapy was left to the discretion of each attending physician; thus, an inherent bias exists, and there were some significant differences at baseline between patients continuing or discontinuing thienopyridine therapy. Moreover, we did not evaluate the restarting of thienopyridine therapy. These factors may have affected clinical outcomes. Finally, we acquired data on bleeding-related deaths, but not on non-fatal-bleeding events, which made it impossible to evaluate the net clinical efficacy of prolonged thienopyridine therapy.
Conclusions
The continuation of thienopyridine therapy beyond 1 year was associated with significantly lower incidences of definite VLST and MI in the SF/PSS group, but had no effect on the incidences of definite VLST, MI, and cardiac death in the non-SF/PSS group after SES implantation.
Conflict of Interest Statement
The authors report no conflicts of interest in regard to this study.
Supplementary Files
Supplementary File 1
Figure S1.
(A) Focus image; (B) inverse image; (C) stent image without catheter or contrast media and stent fracture without restenosis; (D) stent image without catheter or contrast media and stent fracture with restenosis.
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-17-0477
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