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Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice
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Heart, Lung and Circulation (2019) -, -–1443-9506/19/$36.00 https://doi.org/10.1016/j.hlc.2019.10.009
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ORIGINAL ARTICLE
Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice Riley Batchelor, MBBS a,b, Diem Dinh, BAppSc, PhD b, Angela Brennan, BSc, CCRN b, Jeffrey Lefkovits, MBBS, FRACP c, Christopher Reid, MSc, PhD b,d, Stephen J. Duffy, MBBS, PhD, FRACP, MRCP, FCSANZ a,b, Nicholas Cox, MBBS, FRACP b,e, Danny Liew, MBBS, FRACP, PhD, CertHealthEcon b, Dion Stub, MBBS, PhD, FRACP a,b,e,*, on behalf of the VCOR Investigators a
Department of Cardiology, Alfred Health, Melbourne, Vic, Australia Monash University, Melbourne, Vic, Australia c Department of Cardiology, Royal Melbourne Hospital, Melbourne, Vic, Australia d Curtin University, Perth, WA, Australia e Department of Cardiology, Western Health, Melbourne, Vic, Australia b
Received 25 July 2019; received in revised form 30 September 2019; accepted 14 October 2019; online published-ahead-of-print xxx
Background
Stent thrombosis (ST) is an uncommon but serious complication of percutaneous coronary intervention (PCI). The reported rate of definite ST with new generation drug-eluting stents ranges from 0.5 to 1% at 30 days. We aimed to examine the incidence and outcomes of ST in a real-world setting.
Methods
The Victorian Cardiac Outcomes Registry was established in 2012 as a state-wide clinical quality registry, with all PCI capable centres contributing in 2017. Data were collected on 41,137 consecutive PCI procedures from 2013 to 2017. We describe the patient characteristics and clinical outcomes in definite and probable ST at 30 days.
Results
Stent thrombosis occurred in 225 patients (0.55%). Compared to patients without ST, these patients were more likely to be female (32.0% vs. 23.4%, p#0.01) and have a history of diabetes (28.6% vs. 21.9%, p=0.02). ST was more common in patients with severely reduced left ventricular ejection fraction (14.9% vs. 4.6%, p,0.001) and in patients presenting with ST-elevation myocardial infarction, cardiogenic shock and cardiac arrest for their index PCI (all p,0.001). Dual antiplatelet therapy at 30 days was less frequent in patients with ST (84.8% vs. 92.0%, p,0.001), while 30-day mortality was more common: 23.6% versus 2.0% (p,0.001).
Conclusions
Even with contemporary stents and adjunctive medications, ST still occurs following 1 in 200 PCIs, and is associated with increased mortality at 30 days.
Keywords
Stent thrombosis Percutaneous coronary intervention Outcomes
*Corresponding author at: Department of Cardiology, Alfred Health, 55 Commercial Road, Melbourne, Vic 3004, Australia. Tel: 161 3 9076 3263., Email: d.stub@ alfred.org.au Ó 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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Introduction Stent thrombosis (ST) is an uncommon but serious complication of percutaneous coronary intervention (PCI) [1], most frequently occurring within 30 days of the procedure [2]. Despite recent advances in stent implantation technologies and improvements in adjuvant antiplatelet therapy, the rate of ST with second and third generation drug eluting stents (DES) ranges from 0.5 to 1% and carries a mortality rate of 20–30%, with death often due to myocardial infarction [3–6]. Though a low incidence of ST has previously limited characterisation of specific risk factors, multiple observational studies have reported several clinical and procedural predictors for ST following PCI [1,4,7–11]. Early cessation of pharmacological antiplatelet therapy is strongly associated with an increased risk of ST [5,9]. Percutaneous coronary intervention conducted in patients presenting with STelevation myocardial infarction (STEMI) and non-ST segment myocardial infarction (NSTEMI) has also been linked with an increased risk [5,10]. Other predictors of ST are reported to include inappropriate stent length [11], poor renal function [12] and type II diabetes mellitus [13]. Given the significant consequences of complications associated with ST, the present study aimed to examine the incidence of ST in a contemporary population of Australian patients. Improved understanding of the incidence of ST and its complications may assist in earlier identification and management of high-risk patients.
R. Batchelor et al.
adjuvant oral anticoagulant or antiplatelet therapy and procedural characteristics were also collected and compared between the two groups. Within procedural characteristics, lesion complexity was defined according to American College of Cardiology/American Heart Association (ACC/AHA) classification guidelines as A, B1, B2 or C [16]. Clinical outcomes collected at 30 days included all-cause mortality, new stroke, major bleeding, the need for emergency PCI, any target vessel revascularisation or target lesion revascularisation (TLR) and the need for emergency CABG or target vessel CABG. Patients were followed up at 30 days following discharge from the admission in which they underwent PCI. Where information could not be obtained from medical records, the patient or next of kin was contacted via telephone, or information sought from a general practitioner. Bleeding was defined according to the Bleeding Academic Research Consortium (BARC) classification [17], BARC 3 (overt haemorrhage with haemoglobin drop of .3 g/dL, intracranial bleeding, cardiac tamponade or transfusion requirement), or BARC 5 (probable or definite fatal haemorrhage). Univariate analysis was undertaken to compare baseline, procedural, treatment characteristics and clinical outcomes in the ST group compared to the group without ST. Continuous variables are presented as means with standard deviations and categorical variables are expressed as the number of patients with percentages. The Chi-square, t-tests, or MannWhitney U test were used as appropriate to compare categorical and continuous variables and to assess statistical significance. All tests were two-tailed, and we considered a p value ,0.05 statistically significant.
Methods The Victorian Cardiac Outcomes Registry (VCOR) is a statebased, multi-centre clinical quality registry, with the purpose to improve safety and quality of care provided to patients admitted to hospital for cardiovascular conditions. The VCOR methodology has been extensively described previously [14]. In brief, VCOR was established in 2012 and records data across public and private hospitals in Victoria, with all 30 PCI-capable centres contributing in 2017. VCOR is coordinated by Monash University and is governed by a steering committee comprised of representatives from contributing centres. We analysed data from all patients that underwent PCI between 1 January 2013 and 31 December 2017 following institutional ethics approval. Stent thrombosis was defined according to the Academic Research Consortium (ARC) classification as: definite, the presence of acute coronary syndrome (ACS) with angiography or autopsy evidence of thrombus or occlusion; and, probable, an unexplained death following the procedure or acute myocardial infarction (MI) involving the target vessel territory without angiographic or autopsy confirmation [15]. STs classified as possible, defined as any unexplained death occurring at least 30 days following the procedure, were included in the “no ST” group. Baseline demographic characteristics were compared between those that recorded definite or probable ST and those that did not. Treatment strategies including
Results A total of 41,137 consecutive PCI procedures were analysed with 225 definite and probable STs (0.55%) documented during the 5-year study period. Of the 225 STs analysed, 121 (53.8%) were recorded in hospital with the remaining 104 (46.2%) occurring within 30 days. The “no ST group” included 31 cases of possible ST. Baseline clinical characteristics are presented in Table 1. Patients with definite or probable ST at 30 days were more likely to be female (32.0% vs. 23.4%; p,0.01) and present with a range of comorbid conditions, including medicated diabetes mellitus (28.6% vs. 21.9%; p=0.02) and cerebrovascular disease (7.6% vs. 3.7%; p,0.01). Severe left ventricular systolic dysfunction was more common in the ST group (14.9% vs. 4.6%; p,0.001). Patients with ST were more likely to have presented for their index PCI with cardiogenic shock (13.3% vs. 2.3%; p,0.001), out-of-hospital cardiac arrest (5.8% vs. 2.3%; p,0.001) or for primary PCI for STEMI (42.7% vs. 20.7%; p,0.001). Procedural characteristics are described in Table 2 and medication characteristics are described in Table 3. There was no statistically significant difference in the route of access (radial vs. femoral) between the ST and no ST groups. Placement of DES was found to be less common in those with ST at 30 days (75.1% vs. 81.8%; p=0.01).
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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Incidence, Predictors and Clinical Outcomes of Stent Thrombosis
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Table 1 Baseline clinical characteristics.
Age (years)
All patients (n=41137)
ST at 30 days (n=225)
No ST at 30 days (n=40912)
66.0 6 11.9
67.1 6 11.5
66.0 6 11.9
9,656 (23.5)
72 (32.0)
9,584 (23.4)
2013
4,583 (11.1)
17 (7.6)
4,566 (11.2)
2014 2015
7,896 (19.2) 8,840 (21.5)
37 (16.4) 53 (23.6)
7,859 (19.2) 8,787 (21.5)
2016
9,569 (23.3)
59 (26.2)
9,510 (23.2)
2017
10,249 (24.9)
59 (26.2)
10,190 (24.9)
16,175 (39.3)
89 (39.6)
16,086 (39.3)
2 (1, 4)
4 (2, 6)
2 (1, 4)
Female gender
Median length of stay, days (IQR) BMI (kg/m2)
0.16 ,0.01 0.08
Year of PCI
Private hospital
P-value
28.8 6 5.4
29.0 6 5.7
28.8 6 5.4
0.94 ,0.001 0.52
Diabetes mellitus
9,010 (21.9)
64 (28.6)
8,946 (21.9)
Peripheral vascular disease Cerebrovascular disease
1,458 (3.5) 1,532 (3.7)
13 (5.8) 17 (7.6)
1,445 (3.5) 1,515 (3.7)
0.07 ,0.01
13,553 (32.9)
99 (44.2)
13,454 (32.9)
,0.001
3,212 (7.8)
10 (4.5)
3,202 (7.8)
Previous PCI Previous CABG
23,550 (66.3)
101 (48.6)
23,449 (66.4)
Mild (45-50%)
6,686 (18.8)
44 (21.2)
6,642 (18.8)
Moderate (35-44%)
3,599 (10.1)
32 (15.4)
3,567 (10.1)
1,662 (4.7)
31 (14.9)
1,631 (4.6)
29,930 (72.8)
156 (69.3)
29,774 (72.8)
eGFR = 45-60mL/min/1.73m2
4,479 (10.9)
28 (12.4)
4,451 (10.9)
eGFR = 30-45mL/min/1.73m2
2,444 (5.9)
11 (4.9)
2,433 (5.9)
eGFR . 30mL/min/1.73m2
1,019 (2.5)
8 (3.6)
1,011 (2.5)
Severe (,35%) Renal function eGFR . 60mL/min/1.73m2
0.06 ,0.001
LVEF Normal (.50%)
0.02
0.51
Cardiogenic shock
982 (2.4)
30 (13.3)
952 (2.3)
,0.001
Out-of-hospital cardiac arrest
939 (2.3)
13 (5.8)
926 (2.3)
,0.001
8,547 (20.8)
96 (42.7)
8,451 (20.7)
NSTEMI
9,647 (23.5)
45 (20.0)
9,602 (23.5)
UAP
3,034 (7.4)
13 (5.8)
3,021 (7.4)
11,105 (27.0)
30 (13.3)
11,075 (27.1)
8,804 (21.4)
41 (18.2)
8,762 (21.4)
Indication for PCI STEMI
Stable angina Other
,0.001
Values are expressed as mean 6 standard deviation or n (%). Abbreviations: BMI, body mass index; CABG, coronary artery bypass graft; eGFR, estimated glomerular filtration rate; IQR, interquartile range; LVEF, left ventricular ejection fracture; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; ST, stent thrombosis; STEMI, STelevation myocardial infarction; UAP, unstable angina pectoris.
Percutaneous coronary intervention to lesions located in the left anterior descending (LAD) or left main (LM) were more common in the ST group (47.6% vs. 40.6% and 3.6 vs. 1.9%; respectively; p=0.03). Patients with ST were significantly less likely to have been discharged from hospital on dual antiplatelet therapy (DAPT) (90.2% vs. 95.2%; p,0.01) and were more commonly discharged on no antiplatelet agent (1.1% vs. 0.1%; p,0.001). A similar finding was observed for both DAPT at 30 days following index procedure (84.2% vs. 92.0%; p,0.001), as well as for the absence of antiplatelet therapy (6.7% vs. 1.1%; p,0.001).
Clinical outcomes are presented in Table 4 and Figure 1. Stent thrombosis was associated with 23.6% mortality at 30 days, as compared to 2.0% in the no ST group (p,0.001). Major bleeding occurred at a rate of 8.4% in the ST group as compared to 1.1% (p,0.001) in the no ST group. In the 225 patients with ST at 30 days, there were 11 in-hospital major bleeding cases and a further eight major bleeding cases at 30 days (totalling 19 major bleeds at 30 days). DAPT was found to have been discontinued in 10 of the 19 major bleeding cases at 30 days (Table 5). Emergent PCI or CABG was undertaken in the ST group in 20.0% and 4.0% of cases respectively (p,0.001).
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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444 445 446 All patients ST at 30 days No ST at 30 P-value 447 448 PCI access 0.23 449 Brachial/radial 19,949 (48.5) 118 (52.4) 19,831 (48.5) 450 Femoral 21,188 (51.5) 107 (47.6) 21,081 (51.5) 451 Lesion location 0.03 452 RCA 12,694 (30.9) 62 (27.6) 12,632 (30.9) 453 454 LAD 16,734 (40.7) 107 (47.6) 16,627 (40.6) 455 LCx 10,076 (24.5) 47 (20.9) 10,029 (24.5) 456 LM 799 (1.9) 8 (3.6) 791 (1.9) 457 Graft 834 (2.0) 1 (0.4) 833 (2.0) 458 Lesion complexity 0.38 459 A or B1 17,286 (42.0) 88 (39.1) 17,198 (42.0) 460 B2 or C 23,851 (58.0) 137 (60.9) 23,714 (58.0) 461 462 Any DES 33,617 (81.7) 169 (75.1) 33,448 (81.8) 0.01 463 BMS only 4,708 (11.4) 31 (13.8) 4,677 (11.4) 0.27 464 Total stent number 1.3 6 0.8 1.4 6 0.9 1.3 6 0.8 0.20 465 Total stent length (mm) 25.3 6 16.9 26.7 6 19.0 25.3 6 16.9 0.22 466 Intravascular ultrasound 487 (1.2) 8 (3.6) 479 (1.2) 0.01 467 468 Values are expressed as mean 6 standard deviation or n (%). 469 Abbreviations: BMS, bare metal stent; DES, drug-eluting stent; LAD, left anterior descending artery; LCx, left circumflex artery; LM, left main artery; PCI, 470 percutaneous coronary intervention; RCA, right coronary artery; ST, stent thrombosis. 471 472 473 474 475 registry data reflect an incidence of 0.9% at 30 days in patients 476 with bare metal stent (BMS) implantation in 2001 [19] and 0.6% 477 Stent thrombosis is defined by the development of occlusive or in patients with first generation DES in 2005 [20] (0.7% and 0.5% 478 partially occlusive thrombus within or adjacent to a stent placed in the present study, respectively). We found that 42.7% of pa479 during or after PCI [18]. This may be precipitated by several 480 tients with ST had presented for their index PCI with STEMI, as 481 factors that promote slow coronary blood flow, endothelial opposed to 20.7% of patients without ST at 30 days. This 482 injury or hypercoagulability [18]. These factors may broadly be disparity is in keeping with investigation of 3,405 moderate and 483 defined as patient-, procedural-, lesion-, and medication-related. Q3 high risk ACS patients included in the ACUITY trial, an analysis 484 This study investigated the incidence, predictors and clinical that demonstrated an incidence of ST in this population of 1.4% 485 outcomes of ST across a large patient cohort undergoing PCI in at 30 days, and increased risk of patients with high-risk ACS 486 Victoria from 2013 to 2018. The results highlight that definite or [21]. Potential mechanisms for the increased incidence of ST 487 probable ST still occurs in contemporary practice in 0.55% of PCI 488 following primary PCI for STEMI are platelet activation [22] and 489 cases before 30 days post PCI. Despite improved PCI technology impaired absorption of adjuvant antiplatelet therapy in this 490 and practices, ST is an infrequent but nonetheless important setting [23]. 491 complication of PCI. We showed that factors associated with ST included fe492 We found that those with ST were more likely to be female gender (p,0.01), cerebrovascular disease (p,0.01) and 493 male, more likely to suffer from a range of medical comorprevious PCI (p,0.001). In view of emerging data suggesting 494 bidities and less likely to be on DAPT at 30 days. While major that female gender is an independent predictor for mortality 495 bleeding was at a significantly higher rate in the ST group, 496 following PCI [24], a statistically significant difference in the 497 only 19 of 225 ST patients were found to have a major percentage of females within the ST group and no-ST group 498 bleeding event. This study reports a mortality rate of 23.6% is notable. Stent thrombosis was more common in patients 499 in those with ST, and adds to growing understanding of with left ventricular systolic dysfunction (p,0.001), a result 500 patient and procedural risk factors for ST. consistent with previous data on BMS use [25]. Not dissim501 The results of this study are in keeping with previous registry ilar to findings of a recent meta-analysis of patients with type 502 analyses. A German-Italian registry of 2,229 patients with first 2 diabetes undergoing PCI with DES implantation [13], type 503 generation DES reported an incidence of 0.6% of definite and 504 2 diabetes was present at a higher percentage in patients with 505 probable STs at 30 days [8]. Analysis of an Australian cohort of ST than without. Angiographic and procedural features 506 2,919 patients from 2004 to 2006 found an incidence of 0.5% of including lesion complexity (such as bifurcation lesions with 507 definite and probable ST at 30 days [6]. Pooled clinical trial and DES), stent number, stent length and stent underexpansion 508
Table 2 Procedural characteristics.
Discussion
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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Table 3 Medication characteristics. All patients
ST at 30 days
No ST at 30
P-value
24 hours prior to PCI 2,349 (5.7)
15 (6.7)
2,334 (5.7)
0.52
Aspirin
37,313 (90.7)
208 (92.4)
37,105 (90.7)
0.37
Thienopyridine
18,782 (45.7)
88 (39.1)
18,694 (45.7)
0.05
Ticagrelor No antiplatelet
15,204 (37.0) 1,650 (4.0)
96 (42.7) 7 (3.1)
15,108 (36.9) 1,643 (4.0)
0.08 0.49
Oral anticoagulation
Single antiplatelet Dual antiplatelet
7,866 (19.1)
47 (20.9)
7,819 (19.1)
0.50
31,603 (76.8)
171 (76.0)
31,432 (76.8)
0.77
2,806 (6.9)
21 (11.5)
2,785 (6.9)
On discharge from hospital Oral anticoagulation
45 (0.1)
No antiplatelet
2 (1.1)
43 (0.1)
0.10 ,0.001
1,901 (4.7)
16 (8.7)
1,885 (4.7)
38,330 (94.7)
165 (90.2)
38,165 (95.2)
Aspirin
37,666 (95.6)
160 (96.4)
37,506 (95.6)
0.85
Thienopyridine
21,802 (55.3)
72 (43.4)
21,730 (55.4)
,0.01
Ticagrelor
16,450 (41.7)
88 (53.0)
16,362 (41.7)
Single antiplatelet Dual antiplatelet At 30 days
No antiplatelet Single antiplatelet Dual antiplatelet
455 (1.1)
12 (6.7)
443 (1.1)
0.01 ,0.01
0.01 ,0.001
2,728 (6.9)
14 (7.9)
2,714 (6.9)
0.60
36,522 (91.9)
151 (84.8)
36,371 (92.0)
,0.001
Values are expressed as n (%). Abbreviations: PCI, percutaneous coronary intervention; ST, stent thrombosis.
have previously been linked to ST [5,25–28]. Discrepancies in lesion complexity, stent number, and stent length between the two groups did not reach statistical significance in the present study, however. We observed that 84.8% of patients with ST at 30 days remained on DAPT as compared to 92.0% of those without ST (p,0.001). Fewer patients were found to remain on a thienopyridine in the ST group (43.4% vs 55.4%, p,0.01) but there was no difference in the frequency of aspirin use (96.4%
vs 95.6%, p=0.85). The results of this study build on the results of large observational and registry studies reporting discontinuation of antiplatelet therapy as the most important predictor of ST, with one study publishing a hazard ratio of 36.53 (95% confidence interval 7.96–167.77, p,0.01) for ST with cessation of clopidogrel within 30 days in patients with DES [5]. The relationship observed between major bleeding and ST, despite a lower rate of DAPT may be due to the withdrawal of antiplatelet medication in a response to a
Table 4 Clinical outcomes at 30 days. All patients (n=41137)
ST at 30 days (n=225)
No ST at 30 days (n=40912)
P-value
Mortality
889 (2.2)
53 (23.6)
836 (2.0)
,0.001
Stroke
158 (0.4)
7 (3.1)
151 (0.4)
,0.001
Major bleed Emergency PCI
487 (1.2) 233 (0.5)
19 (8.4) 45 (20.0)
468 (1.1) 178 (0.4)
,0.001 ,0.001
37 (0.1)
9 (4.0)
28 (0.1)
,0.001
258 (0.6)
43 (19.1)
215 (0.5)
,0.001
Any TLR
165 (0.4)
42 (18.7)
123 (0.3)
,0.001
Target vessel CABG
133 (0.3)
9 (4.0)
104 (0.3)
,0.001
Emergency CABG Any TVR
Values are expressed as n (%). Abbreviations: CABG, coronary artery bypass graft; PCI, percutaneous coronary intervention; ST, stent thrombosis; TLR, target lesion revascularisation; TVR, target vessel revascularisation.
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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ST at 30 days 25
No ST at 30 days
23.6
20
19.1
20
Clinical outcome rate (%)
639 640 641 642 643 644 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703
R. Batchelor et al.
18.7
15
10
8.4
5
4
3.1 2
1.1
0.4
0.4
4
0.1
0.5
0.3
Any TVR
Any TLR
0.3
0 Mortality
Stroke
Major bleed Emergency PCI
Emergency CABG
Target vessel CABG
Figure 1 Clinical outcomes at 30 days. Abbreviations: PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; TVR, target vessel revascularisation; TLR, target lesion revascularisation; ST, stent thrombosis.
major bleeding event, subsequently placing the patient at higher risk of ST. This is supported by the discontinuation of DAPT in seven of the 11 patients that had an inpatient major bleeding event and went on to develop ST at 30 days. In patients that had a major bleed by 30 days and developed ST, over half had discontinued DAPT (10 of 19). Alternative reasons for the lower rate of DAPT seen in the stent thrombosis group include medication non-adherence, concurrent therapy with oral anticoagulation whereby the patient continued single antiplatelet therapy. There are several limitations and strengths of this study worth noting. This study provides a contemporary analysis of stent thrombosis in the era of third generation drugeluting stents. As most cases of ST occur within 30 days of placement [2], complete 30-day follow-up of medication prescription and clinical outcomes was one further advantage. Thirty (30)-day outcomes included both definite and probable STs. We believe the reported incidence of ST is
likely to be closer to the true incidence as patients suffering silent stent occlusion were included in the analyses. This has been a limitation of previous studies [5,7]. While analyses of a large cohort enable examination of uncommon events such as ST, a limitation of the present study is its retrospective, non-randomised design and subsequent vulnerability to multiple sources of potential bias. Furthermore, given that ST was an uncommon outcome, there was not enough power to conduct a multivariate analysis. Despite this, this descriptive study was able to establish several associations in demographic and procedural data for ST. However, due to its retrospective design, causality cannot be inferred. Second, while use of third generation stents is standard of care in Victoria, VCOR does not collect data detailing specific DES generation; therefore, a comparative safety analysis of stent generation was not possible. Third, while most ST occur within 30 days, late and very-late ST were not captured by this study. One final
Table 5 Major bleeding and dual antiplatelet therapy in patients with ST. ST at 30 days (n=225)
No DAPT 30 days (n=74)
DAPT 30 days (n=147)
P-value
Inpatient major bleed
11 (4.9)
7 (9.5)
4 (2.6)
0.03
30-day major bleed
19 (8.4)
10 (13.5)
9 (6.0)
0.06
Values are expressed as n (%). Abbreviations: DAPT, dual antiplatelet therapy; ST, stent thrombosis.
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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limitation is that while data regarding medication prescription was collected at 30 days, it is difficult to ascertain prevalence of true medication adherence in this population in a registry of this size.
[10]
[11]
Conclusions Stent thrombosis remains an uncommon but important complication of PCI. The results of this registry-based study of a large cohort of unselected patients undergoing PCI suggest that, even with new generation stent technology and adjunctive medication, ST occurs following approximately 1 in every 200 PCIs. In the contemporary setting, ST is associated with increased risk of mortality at 30 days.
Acknowledgements
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The Victorian Cardiac Outcomes Registry (VCOR) was funded by the Victorian Department of Health and Human Services and by a one-off grant from Medibank Private from 2011 to 2014. It is currently funded by the Department of Health and Human Services, Monash University and Victorian Cardiac Clinical Network. Professor Duffy’s work is supported by a NHMRC grant (reference no. 1111170). Professor Reid is supported by a NHMRC Principal Research Fellowship (reference no. 11136372). Associate Professor Stub is supported by a NHF Future Leader Fellowship (reference no. 101908), and a Viertel Foundation Clinical Investigator award. The authors declare no conflicts of interest.
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Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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ORIGINAL ARTICLE
Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice Riley Batchelor, MBBS a,b, Diem Dinh, BAppSc, PhD b, Angela Brennan, BSc, CCRN b, Jeffrey Lefkovits, MBBS, FRACP c, Christopher Reid, MSc, PhD b,d, Stephen J. Duffy, MBBS, PhD, FRACP, MRCP, FCSANZ a,b, Nicholas Cox, MBBS, FRACP b,e, Danny Liew, MBBS, FRACP, PhD, CertHealthEcon b, Dion Stub, MBBS, PhD, FRACP a,b,e,*, on behalf of the VCOR Investigators a
Department of Cardiology, Alfred Health, Melbourne, Vic, Australia Monash University, Melbourne, Vic, Australia c Department of Cardiology, Royal Melbourne Hospital, Melbourne, Vic, Australia d Curtin University, Perth, WA, Australia e Department of Cardiology, Western Health, Melbourne, Vic, Australia b
Received 25 July 2019; received in revised form 30 September 2019; accepted 14 October 2019; online published-ahead-of-print xxx
Background
Stent thrombosis (ST) is an uncommon but serious complication of percutaneous coronary intervention (PCI). The reported rate of definite ST with new generation drug-eluting stents ranges from 0.5 to 1% at 30 days. We aimed to examine the incidence and outcomes of ST in a real-world setting.
Methods
The Victorian Cardiac Outcomes Registry was established in 2012 as a state-wide clinical quality registry, with all PCI capable centres contributing in 2017. Data were collected on 41,137 consecutive PCI procedures from 2013 to 2017. We describe the patient characteristics and clinical outcomes in definite and probable ST at 30 days.
Results
Stent thrombosis occurred in 225 patients (0.55%). Compared to patients without ST, these patients were more likely to be female (32.0% vs. 23.4%, p#0.01) and have a history of diabetes (28.6% vs. 21.9%, p=0.02). ST was more common in patients with severely reduced left ventricular ejection fraction (14.9% vs. 4.6%, p,0.001) and in patients presenting with ST-elevation myocardial infarction, cardiogenic shock and cardiac arrest for their index PCI (all p,0.001). Dual antiplatelet therapy at 30 days was less frequent in patients with ST (84.8% vs. 92.0%, p,0.001), while 30-day mortality was more common: 23.6% versus 2.0% (p,0.001).
Conclusions
Even with contemporary stents and adjunctive medications, ST still occurs following 1 in 200 PCIs, and is associated with increased mortality at 30 days.
Keywords
Stent thrombosis Percutaneous coronary intervention Outcomes
*Corresponding author at: Department of Cardiology, Alfred Health, 55 Commercial Road, Melbourne, Vic 3004, Australia. Tel: 161 3 9076 3263., Email: d.stub@ alfred.org.au Ó 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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Introduction Stent thrombosis (ST) is an uncommon but serious complication of percutaneous coronary intervention (PCI) [1], most frequently occurring within 30 days of the procedure [2]. Despite recent advances in stent implantation technologies and improvements in adjuvant antiplatelet therapy, the rate of ST with second and third generation drug eluting stents (DES) ranges from 0.5 to 1% and carries a mortality rate of 20–30%, with death often due to myocardial infarction [3–6]. Though a low incidence of ST has previously limited characterisation of specific risk factors, multiple observational studies have reported several clinical and procedural predictors for ST following PCI [1,4,7–11]. Early cessation of pharmacological antiplatelet therapy is strongly associated with an increased risk of ST [5,9]. Percutaneous coronary intervention conducted in patients presenting with STelevation myocardial infarction (STEMI) and non-ST segment myocardial infarction (NSTEMI) has also been linked with an increased risk [5,10]. Other predictors of ST are reported to include inappropriate stent length [11], poor renal function [12] and type II diabetes mellitus [13]. Given the significant consequences of complications associated with ST, the present study aimed to examine the incidence of ST in a contemporary population of Australian patients. Improved understanding of the incidence of ST and its complications may assist in earlier identification and management of high-risk patients.
R. Batchelor et al.
adjuvant oral anticoagulant or antiplatelet therapy and procedural characteristics were also collected and compared between the two groups. Within procedural characteristics, lesion complexity was defined according to American College of Cardiology/American Heart Association (ACC/AHA) classification guidelines as A, B1, B2 or C [16]. Clinical outcomes collected at 30 days included all-cause mortality, new stroke, major bleeding, the need for emergency PCI, any target vessel revascularisation or target lesion revascularisation (TLR) and the need for emergency CABG or target vessel CABG. Patients were followed up at 30 days following discharge from the admission in which they underwent PCI. Where information could not be obtained from medical records, the patient or next of kin was contacted via telephone, or information sought from a general practitioner. Bleeding was defined according to the Bleeding Academic Research Consortium (BARC) classification [17], BARC 3 (overt haemorrhage with haemoglobin drop of .3 g/dL, intracranial bleeding, cardiac tamponade or transfusion requirement), or BARC 5 (probable or definite fatal haemorrhage). Univariate analysis was undertaken to compare baseline, procedural, treatment characteristics and clinical outcomes in the ST group compared to the group without ST. Continuous variables are presented as means with standard deviations and categorical variables are expressed as the number of patients with percentages. The Chi-square, t-tests, or MannWhitney U test were used as appropriate to compare categorical and continuous variables and to assess statistical significance. All tests were two-tailed, and we considered a p value ,0.05 statistically significant.
Methods The Victorian Cardiac Outcomes Registry (VCOR) is a statebased, multi-centre clinical quality registry, with the purpose to improve safety and quality of care provided to patients admitted to hospital for cardiovascular conditions. The VCOR methodology has been extensively described previously [14]. In brief, VCOR was established in 2012 and records data across public and private hospitals in Victoria, with all 30 PCI-capable centres contributing in 2017. VCOR is coordinated by Monash University and is governed by a steering committee comprised of representatives from contributing centres. We analysed data from all patients that underwent PCI between 1 January 2013 and 31 December 2017 following institutional ethics approval. Stent thrombosis was defined according to the Academic Research Consortium (ARC) classification as: definite, the presence of acute coronary syndrome (ACS) with angiography or autopsy evidence of thrombus or occlusion; and, probable, an unexplained death following the procedure or acute myocardial infarction (MI) involving the target vessel territory without angiographic or autopsy confirmation [15]. STs classified as possible, defined as any unexplained death occurring at least 30 days following the procedure, were included in the “no ST” group. Baseline demographic characteristics were compared between those that recorded definite or probable ST and those that did not. Treatment strategies including
Results A total of 41,137 consecutive PCI procedures were analysed with 225 definite and probable STs (0.55%) documented during the 5-year study period. Of the 225 STs analysed, 121 (53.8%) were recorded in hospital with the remaining 104 (46.2%) occurring within 30 days. The “no ST group” included 31 cases of possible ST. Baseline clinical characteristics are presented in Table 1. Patients with definite or probable ST at 30 days were more likely to be female (32.0% vs. 23.4%; p,0.01) and present with a range of comorbid conditions, including medicated diabetes mellitus (28.6% vs. 21.9%; p=0.02) and cerebrovascular disease (7.6% vs. 3.7%; p,0.01). Severe left ventricular systolic dysfunction was more common in the ST group (14.9% vs. 4.6%; p,0.001). Patients with ST were more likely to have presented for their index PCI with cardiogenic shock (13.3% vs. 2.3%; p,0.001), out-of-hospital cardiac arrest (5.8% vs. 2.3%; p,0.001) or for primary PCI for STEMI (42.7% vs. 20.7%; p,0.001). Procedural characteristics are described in Table 2 and medication characteristics are described in Table 3. There was no statistically significant difference in the route of access (radial vs. femoral) between the ST and no ST groups. Placement of DES was found to be less common in those with ST at 30 days (75.1% vs. 81.8%; p=0.01).
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313
Table 1 Baseline clinical characteristics.
Age (years)
All patients (n=41137)
ST at 30 days (n=225)
No ST at 30 days (n=40912)
66.0 6 11.9
67.1 6 11.5
66.0 6 11.9
9,656 (23.5)
72 (32.0)
9,584 (23.4)
2013
4,583 (11.1)
17 (7.6)
4,566 (11.2)
2014 2015
7,896 (19.2) 8,840 (21.5)
37 (16.4) 53 (23.6)
7,859 (19.2) 8,787 (21.5)
2016
9,569 (23.3)
59 (26.2)
9,510 (23.2)
2017
10,249 (24.9)
59 (26.2)
10,190 (24.9)
16,175 (39.3)
89 (39.6)
16,086 (39.3)
2 (1, 4)
4 (2, 6)
2 (1, 4)
Female gender
Median length of stay, days (IQR) BMI (kg/m2)
0.16 ,0.01 0.08
Year of PCI
Private hospital
P-value
28.8 6 5.4
29.0 6 5.7
28.8 6 5.4
0.94 ,0.001 0.52
Diabetes mellitus
9,010 (21.9)
64 (28.6)
8,946 (21.9)
Peripheral vascular disease Cerebrovascular disease
1,458 (3.5) 1,532 (3.7)
13 (5.8) 17 (7.6)
1,445 (3.5) 1,515 (3.7)
0.07 ,0.01
13,553 (32.9)
99 (44.2)
13,454 (32.9)
,0.001
3,212 (7.8)
10 (4.5)
3,202 (7.8)
Previous PCI Previous CABG
23,550 (66.3)
101 (48.6)
23,449 (66.4)
Mild (45-50%)
6,686 (18.8)
44 (21.2)
6,642 (18.8)
Moderate (35-44%)
3,599 (10.1)
32 (15.4)
3,567 (10.1)
1,662 (4.7)
31 (14.9)
1,631 (4.6)
29,930 (72.8)
156 (69.3)
29,774 (72.8)
eGFR = 45-60mL/min/1.73m2
4,479 (10.9)
28 (12.4)
4,451 (10.9)
eGFR = 30-45mL/min/1.73m2
2,444 (5.9)
11 (4.9)
2,433 (5.9)
eGFR . 30mL/min/1.73m2
1,019 (2.5)
8 (3.6)
1,011 (2.5)
Severe (,35%) Renal function eGFR . 60mL/min/1.73m2
0.06 ,0.001
LVEF Normal (.50%)
0.02
0.51
Cardiogenic shock
982 (2.4)
30 (13.3)
952 (2.3)
,0.001
Out-of-hospital cardiac arrest
939 (2.3)
13 (5.8)
926 (2.3)
,0.001
8,547 (20.8)
96 (42.7)
8,451 (20.7)
NSTEMI
9,647 (23.5)
45 (20.0)
9,602 (23.5)
UAP
3,034 (7.4)
13 (5.8)
3,021 (7.4)
11,105 (27.0)
30 (13.3)
11,075 (27.1)
8,804 (21.4)
41 (18.2)
8,762 (21.4)
Indication for PCI STEMI
Stable angina Other
,0.001
Values are expressed as mean 6 standard deviation or n (%). Abbreviations: BMI, body mass index; CABG, coronary artery bypass graft; eGFR, estimated glomerular filtration rate; IQR, interquartile range; LVEF, left ventricular ejection fracture; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; ST, stent thrombosis; STEMI, STelevation myocardial infarction; UAP, unstable angina pectoris.
Percutaneous coronary intervention to lesions located in the left anterior descending (LAD) or left main (LM) were more common in the ST group (47.6% vs. 40.6% and 3.6 vs. 1.9%; respectively; p=0.03). Patients with ST were significantly less likely to have been discharged from hospital on dual antiplatelet therapy (DAPT) (90.2% vs. 95.2%; p,0.01) and were more commonly discharged on no antiplatelet agent (1.1% vs. 0.1%; p,0.001). A similar finding was observed for both DAPT at 30 days following index procedure (84.2% vs. 92.0%; p,0.001), as well as for the absence of antiplatelet therapy (6.7% vs. 1.1%; p,0.001).
Clinical outcomes are presented in Table 4 and Figure 1. Stent thrombosis was associated with 23.6% mortality at 30 days, as compared to 2.0% in the no ST group (p,0.001). Major bleeding occurred at a rate of 8.4% in the ST group as compared to 1.1% (p,0.001) in the no ST group. In the 225 patients with ST at 30 days, there were 11 in-hospital major bleeding cases and a further eight major bleeding cases at 30 days (totalling 19 major bleeds at 30 days). DAPT was found to have been discontinued in 10 of the 19 major bleeding cases at 30 days (Table 5). Emergent PCI or CABG was undertaken in the ST group in 20.0% and 4.0% of cases respectively (p,0.001).
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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444 445 446 All patients ST at 30 days No ST at 30 P-value 447 448 PCI access 0.23 449 Brachial/radial 19,949 (48.5) 118 (52.4) 19,831 (48.5) 450 Femoral 21,188 (51.5) 107 (47.6) 21,081 (51.5) 451 Lesion location 0.03 452 RCA 12,694 (30.9) 62 (27.6) 12,632 (30.9) 453 454 LAD 16,734 (40.7) 107 (47.6) 16,627 (40.6) 455 LCx 10,076 (24.5) 47 (20.9) 10,029 (24.5) 456 LM 799 (1.9) 8 (3.6) 791 (1.9) 457 Graft 834 (2.0) 1 (0.4) 833 (2.0) 458 Lesion complexity 0.38 459 A or B1 17,286 (42.0) 88 (39.1) 17,198 (42.0) 460 B2 or C 23,851 (58.0) 137 (60.9) 23,714 (58.0) 461 462 Any DES 33,617 (81.7) 169 (75.1) 33,448 (81.8) 0.01 463 BMS only 4,708 (11.4) 31 (13.8) 4,677 (11.4) 0.27 464 Total stent number 1.3 6 0.8 1.4 6 0.9 1.3 6 0.8 0.20 465 Total stent length (mm) 25.3 6 16.9 26.7 6 19.0 25.3 6 16.9 0.22 466 Intravascular ultrasound 487 (1.2) 8 (3.6) 479 (1.2) 0.01 467 468 Values are expressed as mean 6 standard deviation or n (%). 469 Abbreviations: BMS, bare metal stent; DES, drug-eluting stent; LAD, left anterior descending artery; LCx, left circumflex artery; LM, left main artery; PCI, 470 percutaneous coronary intervention; RCA, right coronary artery; ST, stent thrombosis. 471 472 473 474 475 registry data reflect an incidence of 0.9% at 30 days in patients 476 with bare metal stent (BMS) implantation in 2001 [19] and 0.6% 477 Stent thrombosis is defined by the development of occlusive or in patients with first generation DES in 2005 [20] (0.7% and 0.5% 478 partially occlusive thrombus within or adjacent to a stent placed in the present study, respectively). We found that 42.7% of pa479 during or after PCI [18]. This may be precipitated by several 480 tients with ST had presented for their index PCI with STEMI, as 481 factors that promote slow coronary blood flow, endothelial opposed to 20.7% of patients without ST at 30 days. This 482 injury or hypercoagulability [18]. These factors may broadly be disparity is in keeping with investigation of 3,405 moderate and 483 defined as patient-, procedural-, lesion-, and medication-related. Q3 high risk ACS patients included in the ACUITY trial, an analysis 484 This study investigated the incidence, predictors and clinical that demonstrated an incidence of ST in this population of 1.4% 485 outcomes of ST across a large patient cohort undergoing PCI in at 30 days, and increased risk of patients with high-risk ACS 486 Victoria from 2013 to 2018. The results highlight that definite or [21]. Potential mechanisms for the increased incidence of ST 487 probable ST still occurs in contemporary practice in 0.55% of PCI 488 following primary PCI for STEMI are platelet activation [22] and 489 cases before 30 days post PCI. Despite improved PCI technology impaired absorption of adjuvant antiplatelet therapy in this 490 and practices, ST is an infrequent but nonetheless important setting [23]. 491 complication of PCI. We showed that factors associated with ST included fe492 We found that those with ST were more likely to be female gender (p,0.01), cerebrovascular disease (p,0.01) and 493 male, more likely to suffer from a range of medical comorprevious PCI (p,0.001). In view of emerging data suggesting 494 bidities and less likely to be on DAPT at 30 days. While major that female gender is an independent predictor for mortality 495 bleeding was at a significantly higher rate in the ST group, 496 following PCI [24], a statistically significant difference in the 497 only 19 of 225 ST patients were found to have a major percentage of females within the ST group and no-ST group 498 bleeding event. This study reports a mortality rate of 23.6% is notable. Stent thrombosis was more common in patients 499 in those with ST, and adds to growing understanding of with left ventricular systolic dysfunction (p,0.001), a result 500 patient and procedural risk factors for ST. consistent with previous data on BMS use [25]. Not dissim501 The results of this study are in keeping with previous registry ilar to findings of a recent meta-analysis of patients with type 502 analyses. A German-Italian registry of 2,229 patients with first 2 diabetes undergoing PCI with DES implantation [13], type 503 generation DES reported an incidence of 0.6% of definite and 504 2 diabetes was present at a higher percentage in patients with 505 probable STs at 30 days [8]. Analysis of an Australian cohort of ST than without. Angiographic and procedural features 506 2,919 patients from 2004 to 2006 found an incidence of 0.5% of including lesion complexity (such as bifurcation lesions with 507 definite and probable ST at 30 days [6]. Pooled clinical trial and DES), stent number, stent length and stent underexpansion 508
Table 2 Procedural characteristics.
Discussion
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573
Table 3 Medication characteristics. All patients
ST at 30 days
No ST at 30
P-value
24 hours prior to PCI 2,349 (5.7)
15 (6.7)
2,334 (5.7)
0.52
Aspirin
37,313 (90.7)
208 (92.4)
37,105 (90.7)
0.37
Thienopyridine
18,782 (45.7)
88 (39.1)
18,694 (45.7)
0.05
Ticagrelor No antiplatelet
15,204 (37.0) 1,650 (4.0)
96 (42.7) 7 (3.1)
15,108 (36.9) 1,643 (4.0)
0.08 0.49
Oral anticoagulation
Single antiplatelet Dual antiplatelet
7,866 (19.1)
47 (20.9)
7,819 (19.1)
0.50
31,603 (76.8)
171 (76.0)
31,432 (76.8)
0.77
2,806 (6.9)
21 (11.5)
2,785 (6.9)
On discharge from hospital Oral anticoagulation
45 (0.1)
No antiplatelet
2 (1.1)
43 (0.1)
0.10 ,0.001
1,901 (4.7)
16 (8.7)
1,885 (4.7)
38,330 (94.7)
165 (90.2)
38,165 (95.2)
Aspirin
37,666 (95.6)
160 (96.4)
37,506 (95.6)
0.85
Thienopyridine
21,802 (55.3)
72 (43.4)
21,730 (55.4)
,0.01
Ticagrelor
16,450 (41.7)
88 (53.0)
16,362 (41.7)
Single antiplatelet Dual antiplatelet At 30 days
No antiplatelet Single antiplatelet Dual antiplatelet
455 (1.1)
12 (6.7)
443 (1.1)
0.01 ,0.01
0.01 ,0.001
2,728 (6.9)
14 (7.9)
2,714 (6.9)
0.60
36,522 (91.9)
151 (84.8)
36,371 (92.0)
,0.001
Values are expressed as n (%). Abbreviations: PCI, percutaneous coronary intervention; ST, stent thrombosis.
have previously been linked to ST [5,25–28]. Discrepancies in lesion complexity, stent number, and stent length between the two groups did not reach statistical significance in the present study, however. We observed that 84.8% of patients with ST at 30 days remained on DAPT as compared to 92.0% of those without ST (p,0.001). Fewer patients were found to remain on a thienopyridine in the ST group (43.4% vs 55.4%, p,0.01) but there was no difference in the frequency of aspirin use (96.4%
vs 95.6%, p=0.85). The results of this study build on the results of large observational and registry studies reporting discontinuation of antiplatelet therapy as the most important predictor of ST, with one study publishing a hazard ratio of 36.53 (95% confidence interval 7.96–167.77, p,0.01) for ST with cessation of clopidogrel within 30 days in patients with DES [5]. The relationship observed between major bleeding and ST, despite a lower rate of DAPT may be due to the withdrawal of antiplatelet medication in a response to a
Table 4 Clinical outcomes at 30 days. All patients (n=41137)
ST at 30 days (n=225)
No ST at 30 days (n=40912)
P-value
Mortality
889 (2.2)
53 (23.6)
836 (2.0)
,0.001
Stroke
158 (0.4)
7 (3.1)
151 (0.4)
,0.001
Major bleed Emergency PCI
487 (1.2) 233 (0.5)
19 (8.4) 45 (20.0)
468 (1.1) 178 (0.4)
,0.001 ,0.001
37 (0.1)
9 (4.0)
28 (0.1)
,0.001
258 (0.6)
43 (19.1)
215 (0.5)
,0.001
Any TLR
165 (0.4)
42 (18.7)
123 (0.3)
,0.001
Target vessel CABG
133 (0.3)
9 (4.0)
104 (0.3)
,0.001
Emergency CABG Any TVR
Values are expressed as n (%). Abbreviations: CABG, coronary artery bypass graft; PCI, percutaneous coronary intervention; ST, stent thrombosis; TLR, target lesion revascularisation; TVR, target vessel revascularisation.
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632 633 634 635 636 637 638
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ST at 30 days 25
No ST at 30 days
23.6
20
19.1
20
Clinical outcome rate (%)
639 640 641 642 643 644 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703
R. Batchelor et al.
18.7
15
10
8.4
5
4
3.1 2
1.1
0.4
0.4
4
0.1
0.5
0.3
Any TVR
Any TLR
0.3
0 Mortality
Stroke
Major bleed Emergency PCI
Emergency CABG
Target vessel CABG
Figure 1 Clinical outcomes at 30 days. Abbreviations: PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; TVR, target vessel revascularisation; TLR, target lesion revascularisation; ST, stent thrombosis.
major bleeding event, subsequently placing the patient at higher risk of ST. This is supported by the discontinuation of DAPT in seven of the 11 patients that had an inpatient major bleeding event and went on to develop ST at 30 days. In patients that had a major bleed by 30 days and developed ST, over half had discontinued DAPT (10 of 19). Alternative reasons for the lower rate of DAPT seen in the stent thrombosis group include medication non-adherence, concurrent therapy with oral anticoagulation whereby the patient continued single antiplatelet therapy. There are several limitations and strengths of this study worth noting. This study provides a contemporary analysis of stent thrombosis in the era of third generation drugeluting stents. As most cases of ST occur within 30 days of placement [2], complete 30-day follow-up of medication prescription and clinical outcomes was one further advantage. Thirty (30)-day outcomes included both definite and probable STs. We believe the reported incidence of ST is
likely to be closer to the true incidence as patients suffering silent stent occlusion were included in the analyses. This has been a limitation of previous studies [5,7]. While analyses of a large cohort enable examination of uncommon events such as ST, a limitation of the present study is its retrospective, non-randomised design and subsequent vulnerability to multiple sources of potential bias. Furthermore, given that ST was an uncommon outcome, there was not enough power to conduct a multivariate analysis. Despite this, this descriptive study was able to establish several associations in demographic and procedural data for ST. However, due to its retrospective design, causality cannot be inferred. Second, while use of third generation stents is standard of care in Victoria, VCOR does not collect data detailing specific DES generation; therefore, a comparative safety analysis of stent generation was not possible. Third, while most ST occur within 30 days, late and very-late ST were not captured by this study. One final
Table 5 Major bleeding and dual antiplatelet therapy in patients with ST. ST at 30 days (n=225)
No DAPT 30 days (n=74)
DAPT 30 days (n=147)
P-value
Inpatient major bleed
11 (4.9)
7 (9.5)
4 (2.6)
0.03
30-day major bleed
19 (8.4)
10 (13.5)
9 (6.0)
0.06
Values are expressed as n (%). Abbreviations: DAPT, dual antiplatelet therapy; ST, stent thrombosis.
Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726 727 728 729 730 731 732 733 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 760 761 762 763 764 765 766 767 768
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769 770 771 772 773 774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811 812 813 814 815 816 817 818 819 820 821 822 823 824 825
limitation is that while data regarding medication prescription was collected at 30 days, it is difficult to ascertain prevalence of true medication adherence in this population in a registry of this size.
[10]
[11]
Conclusions Stent thrombosis remains an uncommon but important complication of PCI. The results of this registry-based study of a large cohort of unselected patients undergoing PCI suggest that, even with new generation stent technology and adjunctive medication, ST occurs following approximately 1 in every 200 PCIs. In the contemporary setting, ST is associated with increased risk of mortality at 30 days.
Acknowledgements
Q4
The Victorian Cardiac Outcomes Registry (VCOR) was funded by the Victorian Department of Health and Human Services and by a one-off grant from Medibank Private from 2011 to 2014. It is currently funded by the Department of Health and Human Services, Monash University and Victorian Cardiac Clinical Network. Professor Duffy’s work is supported by a NHMRC grant (reference no. 1111170). Professor Reid is supported by a NHMRC Principal Research Fellowship (reference no. 11136372). Associate Professor Stub is supported by a NHF Future Leader Fellowship (reference no. 101908), and a Viertel Foundation Clinical Investigator award. The authors declare no conflicts of interest.
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Please cite this article in press as: Batchelor R, et al. Incidence, Predictors and Clinical Outcomes of Stent Thrombosis Following Percutaneous Coronary Intervention in Contemporary Practice. Heart, Lung and Circulation (2019), https://doi.org/10.1016/ j.hlc.2019.10.009
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