- Email: [email protected]
Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 48 mm stent versus two overlapping stents showed comparable clinical outcomes
CARREV-01831; No of Pages 4 Cardiovascular Revascularization Medicine xxx (xxxx) xxx
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 48 mm stent versus two overlapping stents showed comparable clinical outcomes Hui Wen Sim a, Elizabeth H. Thong a, Poay Huan Loh a, Chi-Hang Lee a,b, Mark Y. Chan a,b, Adrian F. Low a,b, Edgar L. Tay a,b, Koo Hui Chan a, Huay Cheem Tan a,b, Joshua P. Loh a,b,⁎ a b
Department of Cardiology, National University Heart Center, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore
a r t i c l e
i n f o
Article history: Received 3 January 2020 Received in revised form 6 February 2020 Accepted 10 February 2020 Available online xxxx Keywords: Percutaneous coronary intervention Contemporary drug eluting stent Everolimus eluting stents Overlapping stents Diffuse coronary artery disease
a b s t r a c t Background/purpose: Percutaneous coronary intervention (PCI) of diffuse coronary artery disease (CAD) is associated with higher adverse clinical events. This study aimed to compare the clinical outcomes of patients treated with single long 48 mm contemporary drug eluting stents (SL-DES) versus two overlapping contemporary drug eluting stents (OL-DES) for very-long CAD. Methods/materials: We analyzed the clinical outcome of 117 patients with SL-DES and 101 patients with OL-DES who underwent PCI between 1st July 2013 to 31st December 2016. The primary endpoint was target lesion failure (TLF) at two years, defined as a composite of cardiac mortality, target vessel myocardial infarction and target lesion revascularization. Results: Mean age was 60.8 ± 10.5 years for SL-DES group and 60.5 ± 11.9 years in the OL-DES group. SL-DES has longer mean lesion length as compared to OL-DES (43.1 ± 3.7 mm vs. 41.83 ± 2.3 mm p = 0.003). There was no difference in TLF at two years between SL-DES and OL-DES (5.3% vs. 6.4%, adjusted odds ratio 1.43, 95% CI 0.50– 4.11). There was one case of probable ST in each group. Contrast volume usage was lower for SL-DES than OL-DES in patients who underwent single vessel PCI. Conclusions: Treatment of very-long CAD showed comparable TLF at two years for SL-DES versus OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD. © 2020 Elsevier Inc. All rights reserved.
1. Introduction Implanting multiple overlapping drug eluting stents (DES) has become routine practice in treating diffuse coronary artery disease (CAD) [1–3]. Despite its wide usage, overlapping DES poses an increased risk for adverse clinical and angiographic outcome, especially with first generation DES [4–7]. In animal models, the overlapped DES segment exhibit persistent inflammation, fibrin deposition and delayed endothelization due to increased concentration of drugs and stent polymer [8]. Newer-generation overlapping DES are emerging with better safety outcomes that are comparable with single DES, but with conflicting results [9–12]. This can be due to the heterogeneity of lesion characteristic at baseline with longer lesion length and higher lesion complexity in patients who received overlapping DES as compared to single DES. In addition, there is
⁎ Corresponding author at: Department of Cardiology, National University Heart Center, Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, 119228, Singapore. E-mail address: [email protected] (J.P. Loh).
paucity of real-world data that directly compare the use of contemporary single long DES versus overlapping DES. In the recent years, we were able to address very-long lesions with the availability of 48 mm single long contemporary DES in the market. We aim to compare the two-year clinical outcomes between 48 mm single long contemporary DES versus two overlapping contemporary DES in the treatment of very-long CAD. 2. Methods This is an observational registry from a tertiary care cardiac center. Consecutive patients who were successfully implanted with either single long 48 mm contemporary DES (SL-DES) or two overlapping contemporary DES (OL-DES) for lesion lengths of 38-46 mm from 1st July 2013 to 31st December 2016 were included. Patients with cardiogenic shock at presentation were excluded from the study. We also excluded lesions with diameter of ≤2.0 mm. Percutaneous coronary intervention (PCI) was carried out in accordance with the current standard of practice. The choice of SL-DES versus OL-DES and devices were entirely at the discretion of the primary operators. All patients received dual anti-
https://doi.org/10.1016/j.carrev.2020.02.005 1553-8389/© 2020 Elsevier Inc. All rights reserved.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005
2
H.W. Sim et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx
platelet therapy, which included a loading dose of aspirin and P2Y12 receptor antagonists (clopidogrel, prasugrel or ticagrelor). Dual antiplatelet therapy was administered for at least 12 months following DES placement. Baseline demographics, clinical characteristics, and procedural data were collected retrospectively. Angiographic data was analyzed offline using quantitative coronary angiography analysis by a member of the study team not involved in collecting outcomes. Clinical outcomes at one month, six months, one year, and two years were collected by telephone contacts, clinic visits, electronic medical records and registry database. The primary endpoint of this study was target lesion failure (TLF), defined as a composite of cardiac death, target vessel myocardial infarction (MI), or clinically-driven target lesion revascularisation (TLR). Additional endpoints included major adverse cardiovascular events (MACE; defined as a composite of all-cause mortality, MI, or ischemia driven target vessel revascularisation), definite and probable stent thrombosis (ST), and the individual components of TLF and MACE. Deaths not attributable to another cause were considered cardiac death. ST was classified according to the Academic Research Consortium criteria [13]. For descriptive analyses, we compared baseline demographic, clinical and procedural characteristics of SL-DES versus OL-DES. Categorical variables were shown using frequencies and percentages, and continuous variables were presented using mean and standard deviation. Differences between the groups were compared by using chi-square test for categorical variables and student t-test for continuous variables. Multivariate logistic regression models were constructed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the risk of TLF, MACE and their individual components for SL-DES (reference group) versus OL-DES. Included in the multivariate models were age, gender, diabetes, history of PCI, presentation with MI and heart rate. Kaplan-Meier curves were used to visually assess the differences TLF rates between SL-DES and OL-DES. Data were analyzed with IBM SPSS 21.0 and STATA software 16.0. All statistical tests were conducted at 5% level of significance. 3. Results A total of 117 patients were treated with SL-DES versus 101 patients with OL-DES. All the patients in SL-DES group received 48 mm Xience Xpedition (Abbott Vascular). In the OL-DES group, the following DES were implanted: 51.5% Synergy (Boston Scientific), 18.8% Absorb (Abbott Vascular), 12.9% Xience (Abbott Vascular), 5.9% Combo (OrbusNeich), 5.0% Resolute (Medtronic), 4.0% Biofreedom (Biosensors), 1.0% Promus (Boston Scientific), and 1.0% Ultimaster (Terumo). Follow-up data was available for 99.6% at one month, 98.7% at six months, 97.4% at one year and 95.4% at two years. Baseline demographics and clinical presentations are summarized in Table 1. There were more men, with higher prevalence of previous PCI, strokes/transient ischemic attacks but fewer patients who presented with MI in the SL-DES group as compared to the OL-DES group. The lesion and procedural characteristics are shown in Table 2. SL-DES had longer mean lesion length, more multivessel PCI, larger pre-PCI minimal luminal diameter and more patients with pre-PCI TIMI 3 flow as compared to OL-DES group. There were no significant differences in terms of the procedural time, fluoroscopy time and contrast volume between the two groups. However, when we selected only patients who underwent single vessel PCI, contrast volume usage was significantly lower in SL-DES than OL-DES (128.11 ± 41.25 ml versus 150.52 ± 60.16, p = 0.006). Table 3 depicts the crude event rates at one month, six months, one year and two years. TLF at two years was 5.3% in the SL-DES group versus 6.3% in the OL-DES group. One case of probable ST occurred in each group respectively. There were no differences in the unadjusted and adjusted risk of TLF, MACE and their individual components at two years between SL-DES and OL-DES (Table 4). Similarly, there were no differences in the time to TLF between SL-DES and OL-DES (Fig. 1).
Table 1 Baseline demographics and clinical presentation. Variables, mean or n (%)
SL-DES (n = 117)
OL-DES (n = 101)
Age (year) Male sex Body mass index (kg/m2) Past medical history Current smokers Diabetes mellitus Hypertension Hyperlipidemia History of AMI History of PCI History of CABG History of stroke/TIA History of CKD History of PVD History of COPD Clinical presentation Myocardial infarction Novel P2Y12 inhibitors Systolic blood pressure Diastolic blood pressure Heart rate LVEF
60.75 ± 10.54 106 (90.6) 25.85 ± 4.64
60.54 ± 11.87 82 (81.2) 26.48 ± 5.34
45 (38.5) 46 (39.3) 74 (63.2) 92 (78.6) 44 (37.6) 39 (33.3) 6 (5.1) 12 (10.3) 9 (7.7) 3 (2.6) 2 (1.7)
29 (28.7) 37 (36.6) 63 (62.4) 76 (75.2) 37 (36.6) 12 (11.9) 3 (3.0) 3 (3.0) 12 (11.9) 3 (3.0) 2 (2.0)
48 (41.0) 48 (41.0) 134.99 ± 25.98 76.43 ± 12.50 73.54 ± 15.60 58.62 ± 11.73
55 (54.5) 50 (49.0) 135.15 ± 27.58 79.22 ± 16.55 77.79 ± 13.17 59.82 ± 12.60
p value 0.891 0.044 0.451 0.130 0.684 0.894 0.553 0.882 b0.001 0.425 0.034 0.296 0.855 0.882 0.048 0.209 0.965 0.170 0.038 0.500
AMI: acute myocardial infarction; CABG: coronary artery bypass graft surgery; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; LVEF: left ventricular ejection fraction; OL-DES: overlapping drug eluting stents; PCI: percutaneous coronary intervention; PVD: peripheral vascular disease; SL-DES: single long drug eluting stents; TIA: transient ischemic attack.
4. Discussion This is the first study to compare the clinical outcome at two years between 48 mm contemporary SL-DES versus two OL-DES in the treatment of very-long CAD. We found no difference in TLF and the individual components between the two groups. Diffuse CAD is a highly important prognostic factor in patients undergoing PCI [14]. Covering long lesions with multiple overlapping stents may risk geographical miss, stent fracture and stent thrombosis, especially in the era of bare metal stents and early generation DES [15,16]. Although the practice of overlapping DES is still common now, few studies directly compared overlapping DES with single long DES for diffuse CAD in the contemporary era. The SIRTAX trial (SirolimusEluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization) and LESSON (Long-term comparison of Everolimus-eluting and Sirolimus-eluting Stents for cOronary revascularizatioN) registry found that MACE was higher in patients receiving OL-DES as compared to single DES [7,10]. However, these differences in clinical outcomes were not apparent for patients who were treated with only everolimus or zotarolimus DES, suggesting improvement of safety outcome in newer-generation DES [10–12]. Application of the results from previous studies to patients with diffuse CAD may be challenging due to: i) Posthoc analysis with overlapping DES group accounting for only 13% to 31% of the study cohort; ii) Heterogenicity in the baseline characteristic of subjects with tendencies of the OL-DES group having more complex anatomy; iii) Varying lesion lengths between OL-DES and single DES group. Our study cohort was generally comparable in terms of baseline demographics, procedural and lesion characteristics. Our lesion lengths (OL-DES: 43.1 mm vs SL-DES: 41.8 mm) were statistically but not clinically different, making them applicable to this specific population of very-long CAD. Our study cohort also had a high prevalence of diabetes (36.6%), hypertension (60.3%), chronic kidney disease (9.3%) and patients who presented with MI (45.3%). Given the overall complexity of our patient population, the event rates in our study was considered low and compared favorably with other studies. The low event rates could also be in part due to exclusion of patients who presented with cardiogenic shock in order to assess the true performance of both strategies.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005
H.W. Sim et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx Table 2 Lesion and procedural characteristic. Variables, mean or n (%) Lesion characteristics Lesion length (mm) Location LM/LAD LCx RCA CTO Bifurcation lesion Involving distal LM SVG In-stent restenosis Radial puncture Multivessel PCI Intracoronary imaging Glycoprotein IIb/IIIa Lesion preparation Pre-dilatation Balloon diameter (mm) Maximum balloon pressure (atm) Non-compliant balloon Cutting/scoring balloon Rotational atherectomy Stent optimization Post dilatation Balloon diameter (mm) Maximum balloon pressure (atm) Non-compliant balloon Pre-PCI RVD (mm) Pre-PCI minimal luminal diameter (mm) Pre-PCI diameter stenosis (%) Pre-PCI TIMI 3 flow Post-PCI RVD (mm) Post-PCI minimal luminal diameter (mm) Post-PCI diameter stenosis (%) Post-PCI TIMI 3 flow All patients Procedural time (min) Fluoroscopy time (min) Contrast volume (ml) Patients with single vessel PCI only Procedural time (min) Fluoroscopy time (min) Contrast volume (ml)
3
Table 3 Crude event rates at one month, six months, one year and two years. SL-DES (n = 117)
OL-DES (n = 101)
p value
43.10 ± 3.70
41.83 ± 2.32
0.003 0.074
71 (60.7) 17 (14.5) 29 (24.8) 12 (10.3) 8 (6.8) 3 (2.6) 0 (0) 2 (1.7) 81 (69.2) 38 (32.5) 16 (13.7) 9 (7.7)
76 (74.5) 7 (6.9) 18 (17.8) 7 (6.9) 6 (5.9) 5 (5.0) 0 (0) 2 (2.0) 67 (66.3) 14 (13.9) 18 (17.8) 14 (13.9)
0.385 0.788 0.278 – 0.632 0.648 0.001 0.400 0.139
114 (97.4) 2.49 ± 0.38 14.40 ± 5.02 24 (20.5) 6 (5.1) 2 (1.7)
98 (97.0) 2.42 ± 0.42 14.29 ± 5.42 19 (18.8) 10 (9.9) 1 (1.0)
0.587 0.264 0.871 0.753 0.178 0.555
109 (93.2) 2.88 ± 0.90 20.37 ± 3.96 105 (89.7) 1.96 ± 1.24 0.33 ± 0.30 87.74 ± 10.64 81 (69.2) 2.89 ± 0.62 2.85 ± 0.55 2.22 ± 2.67 114 (97.4)
99 (98.0) 2.99 ± 0.76 20.48 ± 3.67 89 (88.1) 1.76 ± 1.32 0.26 ± 0.27 90.80 ± 10.00 50 (49.5) 2.94 ± 0.48 2.88 ± 0.50 1.89 ± 2.36 95 (94.1)
0.087 0.343 0.841 0.702 0.267 0.071 0.030 0.003 0.550 0.613 0.337 0.211
68.14 ± 37.59 21.97 ± 14.56 150.68 ± 60.32 (n = 79) 59.33 ± 34.20 18.46 ± 11.40 128.11 ± 41.25
70.96 ± 36.26 22.96 ± 13.86 156.48 ± 61.36 (n = 87) 67.92 ± 34.90 22.20 ± 14.30 150.52 ± 60.16
0.575 0.615 0.492 0.112 0.072 0.006
CTO: chronic total occlusion; LAD: left anterior descending artery; LCx: left circumflex artery; LM: left main artery; OL-DES: overlapping drug eluting stents; PCI: percutaneous coronary intervention; RCA: right coronary artery; RVD: reference vessel diameter; SL-DES: single long drug eluting stents; SVG: saphenous venous grafts.
There were two cases of sudden cardiac death that categorized as probable ST (one in each treatment group) without angiographic confirmation. No definite ST observed in both treatment arms of this study. The low number of definite/probable ST in our study could be partly explained by the inclusion of only contemporary DES platform and higher usage of novel P2Y12 inhibitors in our study cohorts (SL-DES 41.0%, OLDES 49.0%). Longer stent length is known to be an independent predictor of ST but this may be mitigated low ST rate from second generation DES [17–19]. A pooled analysis of the SPIRIT and XIENCE V USA trials of patients who underwent planned overlapping stenting with everolimus DES for lesion length ≥35 mm reported only 1.6% definite/probable ST [20]. The pathophysiologic mechanisms underlying the reduction in ST in contemporary DES may be due to more potent antiproliferative agents with better bioavailability and thinner fracture-resistant struts with thromboresistant/bioresorbable polymer [21–22]. Compared to implanting two shorter overlapping stents, single long stents reduce cost, procedural time and contrast volume [23]. However, we found no differences in procedural time, fluoroscopy time and contrast volume between both groups in the total study cohort. This could be explained by a higher number of multivessel PCI in the SL-DES group that increased their overall procedure time and contrast amount.
Clinical outcome n (%)
SL-DES (n = 117)
OL-DES (n = 101)
p value
One month All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
1 (0.9) 1 (0.9) 1 (0.9) 1 (0.9) 0 (0) 1 (0.9) 0 (0) 0 (0) 1 (0.9) 1 (0.9)
1 (1.0) 1 (1.0) 1 (1.0) 1 (1.0) 0 (0) 1 (1.0) 0 (0) 0 (0) 1 (1.0) 1 (1.0)
0.911 0.911 0.911 0.911 – 0.911
Six months All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
3 (2.6) 1 (0.9) 2 (1.7) 2 (1.7) 0 (0) 1 (0.9) 0 (0) 0 (0) 2 (1.7) 4 (3.4)
2 (2.0) 2 (2.0) 2 (2.0) 2 (2.0) 0 (0) 1 (1.0) 1 (1.0) 1 (1.0) 3. (3.0) 3 (3.0)
0.784 0.471 0.873 0.873 – 0.910 0.278 0.278 0.526 0.863
One year All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
3 (2.6) 1 (0.9) 4 (3.4) 2 (1.7) 0 (0) 1 (0.9) 1 (0.9) 1 (0.9) 3 (2.6) 7 (6.0)
2 (2.0) 2 (2.0) 3 (3.1) 3 (3.1) 0 (0) 1 (1.0) 2 (2.0) 2 (2.0) 4 (4.1) 4 (4.2)
0.810 0.454 0.896 0.503 – 0.893 0.454 0.454 0.521 0.542
Two years All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
5 (4.4) 3 (2.7) 7 (6.2) 3 (2.7) 0 (0) 1 (0.9) 2 (1.8) 2 (1.8) 6 (5.3) 12 (10.6)
5 (5.3) 4 (4.3) 4 (4.3) 3 (3.2) 0 (0) 1 (1.0) 2 (2.1) 2 (2.1) 6 (6.4) 8 (8.5)
0.765 0.526 0.536 0.819
0.911 0.911
0.896 0.852 0.852 0.742 0.609
OL-DES: overlapping drug eluting stents; MACE: major adverse cardiovascular events; MI: myocardial infarction; SL-DES: single long drug eluting stents; ST: stent thrombosis; TLF: target lesion failure; TLR: target lesion revascularization; TVR: target vessel revascularization.
When we selected patients with only single vessel PCI, SL-DES had significantly lower contrast volume usage and a trend towards shorter intervention time. Table 4 Risk of adverse event at two years among OL-DES and SL-DES (reference group).
All-cause death Cardiac death Any MI Target vessel MI TLR TVR TLF MACE
Unadjusted OR (95% CI)
Adjusted OR (95% CI)a
1.95 (0.68–5.56) 3.56 (0.93–13.53) 0.54 (0.16–1.85) 0.83 (0.18–3.80) 0.74 (0.12–4.50) 0.74 (0.12–4.50) 1.84 (0.69–4.93) 1.04 (0.47–2.33)
1.78 (0.56–5.64) 3.03 (0.71–13.07) 0.47 (0.12–1.82) 0.54 (0.10–3.02) 0.45 (0.41–4.98) 0.45 (0.41–4.98) 1.43 (0.50–4.11) 0.95 (0.39–2.28)
MACE: major adverse cardiovascular events; MI: myocardial infarction; OL-DES: overlapping drug eluting stents; OR: odds ratio; CI: confidence interval; SL-DES: single long drug eluting stents; ST: stent thrombosis; TLF: target lesion failure; TLR: target lesion revascularization; TVR: target vessel revascularization. a Adjusted for age, sex, diabetes, previous percutaneous coronary intervention, presentation as myocardial infarction, heart rate.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005
4
H.W. Sim et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx
Cheem Tan: Writing - review & editing. Joshua P. Loh: Conceptualization, Methodology, Supervision, Writing - review & editing. References
Fig. 1. Kaplan Meier curves for time to TLF between SL-DES and OL-DES. OL-DES: overlapping drug eluting stents; SL-DES: single long drug eluting stents; TLF: target lesion failure.
This was the first study to compare 48 mm single long everolimus DES versus two overlapping contemporary DES in the treatment of diffuse CAD. However, there were limitations. This was a non-randomized, retrospective study with a small sample size. We observed a large confidence interval between groups which could temper the strength of outcomes and favor a broader hypothesis range. The OL-DES group consisted numerous different stent platforms and we were not able to directly compare stents with similar stent type, properties or drug coating between SL-DES and OL-DES. We did not perform propensity-score matching or other approaches to adjust for confounders known to affect clinical outcomes. Event adjudication was done by the local hospital team in an unblinded fashion but was in accordance to the universally accepted definitions. Our quantitative coronary angiography analyses were not part of a core laboratory assessment. In addition, operators' preferences of PCI strategies without specific mention of reasons might impose potential bias to the study. We did not include patients who had failed implantation of SL-DES. Our follow up was clinical but did not include structured questionnaire on function and symptoms, routine electrocardiogram and stress imaging. There was no routine angiographic and intra-coronary imaging follow-up to identify clinically silent in-stent restenosis. These factors may lead to under-reporting of TVR and TLF. The findings in our single center study may not be generally applicable to all healthcare institution, but the management in our center is in accordance with the current standard of practice. 5. Conclusions Treatment of very-long CAD showed comparable TLF at two years for SL-DES and OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD. Our findings extend current knowledge on the treatment of very-long CAD, but larger randomized controlled trials with longer term follow up are needed in order to draw a definitive conclusion on the best treatment strategy for diffuse CAD. CRediT authorship contribution statement Hui Wen Sim: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing - original draft. Elizabeth H. Thong: Investigation, Writing - original draft. Poay Huan Loh: Writing - review & editing. Chi-Hang Lee: Writing - review & editing. Mark Y. Chan: Writing - review & editing. Adrian F. Low: Writing - review & editing. Edgar L. Tay: Writing - review & editing. Koo Hui Chan: Writing - review & editing. Huay
[1] Aoki J, Ong AT, Rodriguez Granillo GA, McFadden EP, van Mieghem CA, Valgimigli M, et al. “Full metal jacket” (stented length ≥ 64 mm) using drug eluting stents for de novo coronary artery lesions. Am Heart J 2005;150:994–9. [2] Tsagalou E, Chieffo A, Iakovou I, Ge L, Sangiorgi GM, Corvaja N, et al. Multiple overlapping drug-eluting stents to treat diffuse disease of the left anterior descending coronary artery. J Am Coll Cardiol 2005;45:1570–3. [3] Degertekin M, Arampatzis CA, Lemos PA, Saia F, Hoye A, Daemen J, et al. Very long sirolimus-eluting stent implantation for de novo coronary lesions. Am J Cardiol 2004;93:826–9. [4] Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo A, et al. TAXUS VI Investigators. Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice. Circulation 2005;112:3306–13. [5] Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, et al. TAXUS V Investigators. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. JAMA 2005;294:1215–23. [6] Kereiakes DJ, Wang H, Popma JJ, Kuntz RE, Donohoe DJ, Schofer J, et al. Periprocedural and late consequences of overlapping Cypher sirolimus-eluting stents: pooled analysis of five clinical trials. J Am Coll Cardiol 2006;48:21–31. [7] Räber L, Jüni P, Löffel L, Wandel S, Cook S, Wenaweser P, et al. Impact of stent overlap on angiographic and long-term clinical outcome in patients undergoing drug eluting stent implantation. J Am Coll Cardiol 2010;55:1178–88. [8] Finn AV, Kolodgie FD, Harnek J, Guerrero LJ, Acampado E, Tefera K, et al. Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents. Circulation 2005;112:270–8. [9] Kitabata H, Loh JP, Pendyala LK, Badr S, Dvir D, Barbash IM, et al. Safety and efficacy outcomes of overlapping second-generation everolimus-eluting stents versus first generation drug-eluting stents. Am J Cardiol 2013;112:1093–8. [10] O’Sullivan CJ, Stefanini GG, Räber L, Heg D, Taniwaki M, Kalesan B, et al. Impact of stent overlap on long-term clinical outcomes in patients treated with newer generation drug-eluting stents. EuroIntervention 2014;9:1076–84. [11] Farooq V, Vranckx P, Mauri L, Cutlip DE, Belardi J, Silber S, et al. Impact of overlapping newer generation drug-eluting stents on clinical and angiographic outcomes: pooled analysis of five trials from the international Global RESOLUTE Program. Heart 2013;99:626–33. [12] Mori N, Okamoto N, Tanaka A, Yano M, Makino N, Egami Y, et al. Comparison of angiographic and 1-year outcomes between a long single stent and overlapping double stents in patients with newer-generation drug-eluting stents for long narrowings. Am J Cardiol 2016;117:1724–8. [13] Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardised definitions. Circulation 2007;115:2344–51. [14] Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, et al. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005;1:219–27. [15] Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–30. [16] Doi H, Maehara A, Mintz GS, Tsujita K, Kubo T, Castellanos C, et al. Classification and potential mechanisms of intravascular ultrasound patterns of stent fracture. Am J Cardiol 2009;103:818–23. [17] Suh J, Park DW, Lee JY, Jung IH, Lee SW, Kim YH, et al. The relationship and threshold of stent length with regard to risk of stent thrombosis after drug-eluting stent implantation. JACC Cardiovasc Interv 2010;3:383–9. [18] Kedhi E, Stone GW, Kereiakes DJ, Serruys PW, Parise H, Fahy M, et al. Stent thrombosis: insights on outcomes, predictors and impact of dual antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials. Eurointervention 2012;8:599–606. [19] Baber U, Mehran R, Sharma SK, Brar S, Yu J, Suh JW, et al. Impact of the everolimuseluting stent on stent thrombosis: a meta-analysis of 13 randomized trials. J Am Coll Cardiol 2011;58:1569–77. [20] Bouras G, Jhamnani S, Ng VG, Haimi I, Mao V, Deible R, et al. Clinical outcomes after PCI treatment of very long lesions with the XIENCE V everolimus eluting stent; pooled analysis from the SPIRIT and XIENCE V USA prospective multicenter trials. Catheter Cardiovasc Interv 2017;89:984–91. [21] Choi HH, Kim JS, Yoon DH, Hong KS, Kim TH, Kim BK, et al. Favorable neointimal coverage in everolimus-eluting stent at 9 months after stent implantation: comparison with sirolimus-eluting stent using optical coherence tomography. Int J Cardiovasc Imaging 2012;28:491–7. [22] Gutiérrez-Chico JL, van Geuns RJ, Regar E, van der Giessen WJ, Kelbæk H, Saunamäki K, et al. Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial. Eur Heart J 2011;32:2454–63. [23] Hoffmann R, Herrmann G, Silber S, Braun P, Werner GS, Hennen B, et al. IMPact Upon Long Lesion StEnting Study Group. Randomized comparison of success and adverse event rates and cost effectiveness of one long versus two short stents for treatment of long coronary narrowings. Am J Cardiol 2002;90:460–4.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 48 mm stent versus two overlapping stents showed comparable clinical outcomes Hui Wen Sim a, Elizabeth H. Thong a, Poay Huan Loh a, Chi-Hang Lee a,b, Mark Y. Chan a,b, Adrian F. Low a,b, Edgar L. Tay a,b, Koo Hui Chan a, Huay Cheem Tan a,b, Joshua P. Loh a,b,⁎ a b
Department of Cardiology, National University Heart Center, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore
a r t i c l e
i n f o
Article history: Received 3 January 2020 Received in revised form 6 February 2020 Accepted 10 February 2020 Available online xxxx Keywords: Percutaneous coronary intervention Contemporary drug eluting stent Everolimus eluting stents Overlapping stents Diffuse coronary artery disease
a b s t r a c t Background/purpose: Percutaneous coronary intervention (PCI) of diffuse coronary artery disease (CAD) is associated with higher adverse clinical events. This study aimed to compare the clinical outcomes of patients treated with single long 48 mm contemporary drug eluting stents (SL-DES) versus two overlapping contemporary drug eluting stents (OL-DES) for very-long CAD. Methods/materials: We analyzed the clinical outcome of 117 patients with SL-DES and 101 patients with OL-DES who underwent PCI between 1st July 2013 to 31st December 2016. The primary endpoint was target lesion failure (TLF) at two years, defined as a composite of cardiac mortality, target vessel myocardial infarction and target lesion revascularization. Results: Mean age was 60.8 ± 10.5 years for SL-DES group and 60.5 ± 11.9 years in the OL-DES group. SL-DES has longer mean lesion length as compared to OL-DES (43.1 ± 3.7 mm vs. 41.83 ± 2.3 mm p = 0.003). There was no difference in TLF at two years between SL-DES and OL-DES (5.3% vs. 6.4%, adjusted odds ratio 1.43, 95% CI 0.50– 4.11). There was one case of probable ST in each group. Contrast volume usage was lower for SL-DES than OL-DES in patients who underwent single vessel PCI. Conclusions: Treatment of very-long CAD showed comparable TLF at two years for SL-DES versus OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD. © 2020 Elsevier Inc. All rights reserved.
1. Introduction Implanting multiple overlapping drug eluting stents (DES) has become routine practice in treating diffuse coronary artery disease (CAD) [1–3]. Despite its wide usage, overlapping DES poses an increased risk for adverse clinical and angiographic outcome, especially with first generation DES [4–7]. In animal models, the overlapped DES segment exhibit persistent inflammation, fibrin deposition and delayed endothelization due to increased concentration of drugs and stent polymer [8]. Newer-generation overlapping DES are emerging with better safety outcomes that are comparable with single DES, but with conflicting results [9–12]. This can be due to the heterogeneity of lesion characteristic at baseline with longer lesion length and higher lesion complexity in patients who received overlapping DES as compared to single DES. In addition, there is
⁎ Corresponding author at: Department of Cardiology, National University Heart Center, Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, 119228, Singapore. E-mail address: [email protected] (J.P. Loh).
paucity of real-world data that directly compare the use of contemporary single long DES versus overlapping DES. In the recent years, we were able to address very-long lesions with the availability of 48 mm single long contemporary DES in the market. We aim to compare the two-year clinical outcomes between 48 mm single long contemporary DES versus two overlapping contemporary DES in the treatment of very-long CAD. 2. Methods This is an observational registry from a tertiary care cardiac center. Consecutive patients who were successfully implanted with either single long 48 mm contemporary DES (SL-DES) or two overlapping contemporary DES (OL-DES) for lesion lengths of 38-46 mm from 1st July 2013 to 31st December 2016 were included. Patients with cardiogenic shock at presentation were excluded from the study. We also excluded lesions with diameter of ≤2.0 mm. Percutaneous coronary intervention (PCI) was carried out in accordance with the current standard of practice. The choice of SL-DES versus OL-DES and devices were entirely at the discretion of the primary operators. All patients received dual anti-
https://doi.org/10.1016/j.carrev.2020.02.005 1553-8389/© 2020 Elsevier Inc. All rights reserved.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005
2
H.W. Sim et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx
platelet therapy, which included a loading dose of aspirin and P2Y12 receptor antagonists (clopidogrel, prasugrel or ticagrelor). Dual antiplatelet therapy was administered for at least 12 months following DES placement. Baseline demographics, clinical characteristics, and procedural data were collected retrospectively. Angiographic data was analyzed offline using quantitative coronary angiography analysis by a member of the study team not involved in collecting outcomes. Clinical outcomes at one month, six months, one year, and two years were collected by telephone contacts, clinic visits, electronic medical records and registry database. The primary endpoint of this study was target lesion failure (TLF), defined as a composite of cardiac death, target vessel myocardial infarction (MI), or clinically-driven target lesion revascularisation (TLR). Additional endpoints included major adverse cardiovascular events (MACE; defined as a composite of all-cause mortality, MI, or ischemia driven target vessel revascularisation), definite and probable stent thrombosis (ST), and the individual components of TLF and MACE. Deaths not attributable to another cause were considered cardiac death. ST was classified according to the Academic Research Consortium criteria [13]. For descriptive analyses, we compared baseline demographic, clinical and procedural characteristics of SL-DES versus OL-DES. Categorical variables were shown using frequencies and percentages, and continuous variables were presented using mean and standard deviation. Differences between the groups were compared by using chi-square test for categorical variables and student t-test for continuous variables. Multivariate logistic regression models were constructed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the risk of TLF, MACE and their individual components for SL-DES (reference group) versus OL-DES. Included in the multivariate models were age, gender, diabetes, history of PCI, presentation with MI and heart rate. Kaplan-Meier curves were used to visually assess the differences TLF rates between SL-DES and OL-DES. Data were analyzed with IBM SPSS 21.0 and STATA software 16.0. All statistical tests were conducted at 5% level of significance. 3. Results A total of 117 patients were treated with SL-DES versus 101 patients with OL-DES. All the patients in SL-DES group received 48 mm Xience Xpedition (Abbott Vascular). In the OL-DES group, the following DES were implanted: 51.5% Synergy (Boston Scientific), 18.8% Absorb (Abbott Vascular), 12.9% Xience (Abbott Vascular), 5.9% Combo (OrbusNeich), 5.0% Resolute (Medtronic), 4.0% Biofreedom (Biosensors), 1.0% Promus (Boston Scientific), and 1.0% Ultimaster (Terumo). Follow-up data was available for 99.6% at one month, 98.7% at six months, 97.4% at one year and 95.4% at two years. Baseline demographics and clinical presentations are summarized in Table 1. There were more men, with higher prevalence of previous PCI, strokes/transient ischemic attacks but fewer patients who presented with MI in the SL-DES group as compared to the OL-DES group. The lesion and procedural characteristics are shown in Table 2. SL-DES had longer mean lesion length, more multivessel PCI, larger pre-PCI minimal luminal diameter and more patients with pre-PCI TIMI 3 flow as compared to OL-DES group. There were no significant differences in terms of the procedural time, fluoroscopy time and contrast volume between the two groups. However, when we selected only patients who underwent single vessel PCI, contrast volume usage was significantly lower in SL-DES than OL-DES (128.11 ± 41.25 ml versus 150.52 ± 60.16, p = 0.006). Table 3 depicts the crude event rates at one month, six months, one year and two years. TLF at two years was 5.3% in the SL-DES group versus 6.3% in the OL-DES group. One case of probable ST occurred in each group respectively. There were no differences in the unadjusted and adjusted risk of TLF, MACE and their individual components at two years between SL-DES and OL-DES (Table 4). Similarly, there were no differences in the time to TLF between SL-DES and OL-DES (Fig. 1).
Table 1 Baseline demographics and clinical presentation. Variables, mean or n (%)
SL-DES (n = 117)
OL-DES (n = 101)
Age (year) Male sex Body mass index (kg/m2) Past medical history Current smokers Diabetes mellitus Hypertension Hyperlipidemia History of AMI History of PCI History of CABG History of stroke/TIA History of CKD History of PVD History of COPD Clinical presentation Myocardial infarction Novel P2Y12 inhibitors Systolic blood pressure Diastolic blood pressure Heart rate LVEF
60.75 ± 10.54 106 (90.6) 25.85 ± 4.64
60.54 ± 11.87 82 (81.2) 26.48 ± 5.34
45 (38.5) 46 (39.3) 74 (63.2) 92 (78.6) 44 (37.6) 39 (33.3) 6 (5.1) 12 (10.3) 9 (7.7) 3 (2.6) 2 (1.7)
29 (28.7) 37 (36.6) 63 (62.4) 76 (75.2) 37 (36.6) 12 (11.9) 3 (3.0) 3 (3.0) 12 (11.9) 3 (3.0) 2 (2.0)
48 (41.0) 48 (41.0) 134.99 ± 25.98 76.43 ± 12.50 73.54 ± 15.60 58.62 ± 11.73
55 (54.5) 50 (49.0) 135.15 ± 27.58 79.22 ± 16.55 77.79 ± 13.17 59.82 ± 12.60
p value 0.891 0.044 0.451 0.130 0.684 0.894 0.553 0.882 b0.001 0.425 0.034 0.296 0.855 0.882 0.048 0.209 0.965 0.170 0.038 0.500
AMI: acute myocardial infarction; CABG: coronary artery bypass graft surgery; COPD: chronic obstructive pulmonary disease; CKD: chronic kidney disease; LVEF: left ventricular ejection fraction; OL-DES: overlapping drug eluting stents; PCI: percutaneous coronary intervention; PVD: peripheral vascular disease; SL-DES: single long drug eluting stents; TIA: transient ischemic attack.
4. Discussion This is the first study to compare the clinical outcome at two years between 48 mm contemporary SL-DES versus two OL-DES in the treatment of very-long CAD. We found no difference in TLF and the individual components between the two groups. Diffuse CAD is a highly important prognostic factor in patients undergoing PCI [14]. Covering long lesions with multiple overlapping stents may risk geographical miss, stent fracture and stent thrombosis, especially in the era of bare metal stents and early generation DES [15,16]. Although the practice of overlapping DES is still common now, few studies directly compared overlapping DES with single long DES for diffuse CAD in the contemporary era. The SIRTAX trial (SirolimusEluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization) and LESSON (Long-term comparison of Everolimus-eluting and Sirolimus-eluting Stents for cOronary revascularizatioN) registry found that MACE was higher in patients receiving OL-DES as compared to single DES [7,10]. However, these differences in clinical outcomes were not apparent for patients who were treated with only everolimus or zotarolimus DES, suggesting improvement of safety outcome in newer-generation DES [10–12]. Application of the results from previous studies to patients with diffuse CAD may be challenging due to: i) Posthoc analysis with overlapping DES group accounting for only 13% to 31% of the study cohort; ii) Heterogenicity in the baseline characteristic of subjects with tendencies of the OL-DES group having more complex anatomy; iii) Varying lesion lengths between OL-DES and single DES group. Our study cohort was generally comparable in terms of baseline demographics, procedural and lesion characteristics. Our lesion lengths (OL-DES: 43.1 mm vs SL-DES: 41.8 mm) were statistically but not clinically different, making them applicable to this specific population of very-long CAD. Our study cohort also had a high prevalence of diabetes (36.6%), hypertension (60.3%), chronic kidney disease (9.3%) and patients who presented with MI (45.3%). Given the overall complexity of our patient population, the event rates in our study was considered low and compared favorably with other studies. The low event rates could also be in part due to exclusion of patients who presented with cardiogenic shock in order to assess the true performance of both strategies.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005
H.W. Sim et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx Table 2 Lesion and procedural characteristic. Variables, mean or n (%) Lesion characteristics Lesion length (mm) Location LM/LAD LCx RCA CTO Bifurcation lesion Involving distal LM SVG In-stent restenosis Radial puncture Multivessel PCI Intracoronary imaging Glycoprotein IIb/IIIa Lesion preparation Pre-dilatation Balloon diameter (mm) Maximum balloon pressure (atm) Non-compliant balloon Cutting/scoring balloon Rotational atherectomy Stent optimization Post dilatation Balloon diameter (mm) Maximum balloon pressure (atm) Non-compliant balloon Pre-PCI RVD (mm) Pre-PCI minimal luminal diameter (mm) Pre-PCI diameter stenosis (%) Pre-PCI TIMI 3 flow Post-PCI RVD (mm) Post-PCI minimal luminal diameter (mm) Post-PCI diameter stenosis (%) Post-PCI TIMI 3 flow All patients Procedural time (min) Fluoroscopy time (min) Contrast volume (ml) Patients with single vessel PCI only Procedural time (min) Fluoroscopy time (min) Contrast volume (ml)
3
Table 3 Crude event rates at one month, six months, one year and two years. SL-DES (n = 117)
OL-DES (n = 101)
p value
43.10 ± 3.70
41.83 ± 2.32
0.003 0.074
71 (60.7) 17 (14.5) 29 (24.8) 12 (10.3) 8 (6.8) 3 (2.6) 0 (0) 2 (1.7) 81 (69.2) 38 (32.5) 16 (13.7) 9 (7.7)
76 (74.5) 7 (6.9) 18 (17.8) 7 (6.9) 6 (5.9) 5 (5.0) 0 (0) 2 (2.0) 67 (66.3) 14 (13.9) 18 (17.8) 14 (13.9)
0.385 0.788 0.278 – 0.632 0.648 0.001 0.400 0.139
114 (97.4) 2.49 ± 0.38 14.40 ± 5.02 24 (20.5) 6 (5.1) 2 (1.7)
98 (97.0) 2.42 ± 0.42 14.29 ± 5.42 19 (18.8) 10 (9.9) 1 (1.0)
0.587 0.264 0.871 0.753 0.178 0.555
109 (93.2) 2.88 ± 0.90 20.37 ± 3.96 105 (89.7) 1.96 ± 1.24 0.33 ± 0.30 87.74 ± 10.64 81 (69.2) 2.89 ± 0.62 2.85 ± 0.55 2.22 ± 2.67 114 (97.4)
99 (98.0) 2.99 ± 0.76 20.48 ± 3.67 89 (88.1) 1.76 ± 1.32 0.26 ± 0.27 90.80 ± 10.00 50 (49.5) 2.94 ± 0.48 2.88 ± 0.50 1.89 ± 2.36 95 (94.1)
0.087 0.343 0.841 0.702 0.267 0.071 0.030 0.003 0.550 0.613 0.337 0.211
68.14 ± 37.59 21.97 ± 14.56 150.68 ± 60.32 (n = 79) 59.33 ± 34.20 18.46 ± 11.40 128.11 ± 41.25
70.96 ± 36.26 22.96 ± 13.86 156.48 ± 61.36 (n = 87) 67.92 ± 34.90 22.20 ± 14.30 150.52 ± 60.16
0.575 0.615 0.492 0.112 0.072 0.006
CTO: chronic total occlusion; LAD: left anterior descending artery; LCx: left circumflex artery; LM: left main artery; OL-DES: overlapping drug eluting stents; PCI: percutaneous coronary intervention; RCA: right coronary artery; RVD: reference vessel diameter; SL-DES: single long drug eluting stents; SVG: saphenous venous grafts.
There were two cases of sudden cardiac death that categorized as probable ST (one in each treatment group) without angiographic confirmation. No definite ST observed in both treatment arms of this study. The low number of definite/probable ST in our study could be partly explained by the inclusion of only contemporary DES platform and higher usage of novel P2Y12 inhibitors in our study cohorts (SL-DES 41.0%, OLDES 49.0%). Longer stent length is known to be an independent predictor of ST but this may be mitigated low ST rate from second generation DES [17–19]. A pooled analysis of the SPIRIT and XIENCE V USA trials of patients who underwent planned overlapping stenting with everolimus DES for lesion length ≥35 mm reported only 1.6% definite/probable ST [20]. The pathophysiologic mechanisms underlying the reduction in ST in contemporary DES may be due to more potent antiproliferative agents with better bioavailability and thinner fracture-resistant struts with thromboresistant/bioresorbable polymer [21–22]. Compared to implanting two shorter overlapping stents, single long stents reduce cost, procedural time and contrast volume [23]. However, we found no differences in procedural time, fluoroscopy time and contrast volume between both groups in the total study cohort. This could be explained by a higher number of multivessel PCI in the SL-DES group that increased their overall procedure time and contrast amount.
Clinical outcome n (%)
SL-DES (n = 117)
OL-DES (n = 101)
p value
One month All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
1 (0.9) 1 (0.9) 1 (0.9) 1 (0.9) 0 (0) 1 (0.9) 0 (0) 0 (0) 1 (0.9) 1 (0.9)
1 (1.0) 1 (1.0) 1 (1.0) 1 (1.0) 0 (0) 1 (1.0) 0 (0) 0 (0) 1 (1.0) 1 (1.0)
0.911 0.911 0.911 0.911 – 0.911
Six months All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
3 (2.6) 1 (0.9) 2 (1.7) 2 (1.7) 0 (0) 1 (0.9) 0 (0) 0 (0) 2 (1.7) 4 (3.4)
2 (2.0) 2 (2.0) 2 (2.0) 2 (2.0) 0 (0) 1 (1.0) 1 (1.0) 1 (1.0) 3. (3.0) 3 (3.0)
0.784 0.471 0.873 0.873 – 0.910 0.278 0.278 0.526 0.863
One year All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
3 (2.6) 1 (0.9) 4 (3.4) 2 (1.7) 0 (0) 1 (0.9) 1 (0.9) 1 (0.9) 3 (2.6) 7 (6.0)
2 (2.0) 2 (2.0) 3 (3.1) 3 (3.1) 0 (0) 1 (1.0) 2 (2.0) 2 (2.0) 4 (4.1) 4 (4.2)
0.810 0.454 0.896 0.503 – 0.893 0.454 0.454 0.521 0.542
Two years All-cause death Cardiac death Any MI Target vessel MI Definite ST Probable ST TLR TVR TLF MACE
5 (4.4) 3 (2.7) 7 (6.2) 3 (2.7) 0 (0) 1 (0.9) 2 (1.8) 2 (1.8) 6 (5.3) 12 (10.6)
5 (5.3) 4 (4.3) 4 (4.3) 3 (3.2) 0 (0) 1 (1.0) 2 (2.1) 2 (2.1) 6 (6.4) 8 (8.5)
0.765 0.526 0.536 0.819
0.911 0.911
0.896 0.852 0.852 0.742 0.609
OL-DES: overlapping drug eluting stents; MACE: major adverse cardiovascular events; MI: myocardial infarction; SL-DES: single long drug eluting stents; ST: stent thrombosis; TLF: target lesion failure; TLR: target lesion revascularization; TVR: target vessel revascularization.
When we selected patients with only single vessel PCI, SL-DES had significantly lower contrast volume usage and a trend towards shorter intervention time. Table 4 Risk of adverse event at two years among OL-DES and SL-DES (reference group).
All-cause death Cardiac death Any MI Target vessel MI TLR TVR TLF MACE
Unadjusted OR (95% CI)
Adjusted OR (95% CI)a
1.95 (0.68–5.56) 3.56 (0.93–13.53) 0.54 (0.16–1.85) 0.83 (0.18–3.80) 0.74 (0.12–4.50) 0.74 (0.12–4.50) 1.84 (0.69–4.93) 1.04 (0.47–2.33)
1.78 (0.56–5.64) 3.03 (0.71–13.07) 0.47 (0.12–1.82) 0.54 (0.10–3.02) 0.45 (0.41–4.98) 0.45 (0.41–4.98) 1.43 (0.50–4.11) 0.95 (0.39–2.28)
MACE: major adverse cardiovascular events; MI: myocardial infarction; OL-DES: overlapping drug eluting stents; OR: odds ratio; CI: confidence interval; SL-DES: single long drug eluting stents; ST: stent thrombosis; TLF: target lesion failure; TLR: target lesion revascularization; TVR: target vessel revascularization. a Adjusted for age, sex, diabetes, previous percutaneous coronary intervention, presentation as myocardial infarction, heart rate.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005
4
H.W. Sim et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx
Cheem Tan: Writing - review & editing. Joshua P. Loh: Conceptualization, Methodology, Supervision, Writing - review & editing. References
Fig. 1. Kaplan Meier curves for time to TLF between SL-DES and OL-DES. OL-DES: overlapping drug eluting stents; SL-DES: single long drug eluting stents; TLF: target lesion failure.
This was the first study to compare 48 mm single long everolimus DES versus two overlapping contemporary DES in the treatment of diffuse CAD. However, there were limitations. This was a non-randomized, retrospective study with a small sample size. We observed a large confidence interval between groups which could temper the strength of outcomes and favor a broader hypothesis range. The OL-DES group consisted numerous different stent platforms and we were not able to directly compare stents with similar stent type, properties or drug coating between SL-DES and OL-DES. We did not perform propensity-score matching or other approaches to adjust for confounders known to affect clinical outcomes. Event adjudication was done by the local hospital team in an unblinded fashion but was in accordance to the universally accepted definitions. Our quantitative coronary angiography analyses were not part of a core laboratory assessment. In addition, operators' preferences of PCI strategies without specific mention of reasons might impose potential bias to the study. We did not include patients who had failed implantation of SL-DES. Our follow up was clinical but did not include structured questionnaire on function and symptoms, routine electrocardiogram and stress imaging. There was no routine angiographic and intra-coronary imaging follow-up to identify clinically silent in-stent restenosis. These factors may lead to under-reporting of TVR and TLF. The findings in our single center study may not be generally applicable to all healthcare institution, but the management in our center is in accordance with the current standard of practice. 5. Conclusions Treatment of very-long CAD showed comparable TLF at two years for SL-DES and OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD. Our findings extend current knowledge on the treatment of very-long CAD, but larger randomized controlled trials with longer term follow up are needed in order to draw a definitive conclusion on the best treatment strategy for diffuse CAD. CRediT authorship contribution statement Hui Wen Sim: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing - original draft. Elizabeth H. Thong: Investigation, Writing - original draft. Poay Huan Loh: Writing - review & editing. Chi-Hang Lee: Writing - review & editing. Mark Y. Chan: Writing - review & editing. Adrian F. Low: Writing - review & editing. Edgar L. Tay: Writing - review & editing. Koo Hui Chan: Writing - review & editing. Huay
[1] Aoki J, Ong AT, Rodriguez Granillo GA, McFadden EP, van Mieghem CA, Valgimigli M, et al. “Full metal jacket” (stented length ≥ 64 mm) using drug eluting stents for de novo coronary artery lesions. Am Heart J 2005;150:994–9. [2] Tsagalou E, Chieffo A, Iakovou I, Ge L, Sangiorgi GM, Corvaja N, et al. Multiple overlapping drug-eluting stents to treat diffuse disease of the left anterior descending coronary artery. J Am Coll Cardiol 2005;45:1570–3. [3] Degertekin M, Arampatzis CA, Lemos PA, Saia F, Hoye A, Daemen J, et al. Very long sirolimus-eluting stent implantation for de novo coronary lesions. Am J Cardiol 2004;93:826–9. [4] Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo A, et al. TAXUS VI Investigators. Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice. Circulation 2005;112:3306–13. [5] Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, et al. TAXUS V Investigators. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. JAMA 2005;294:1215–23. [6] Kereiakes DJ, Wang H, Popma JJ, Kuntz RE, Donohoe DJ, Schofer J, et al. Periprocedural and late consequences of overlapping Cypher sirolimus-eluting stents: pooled analysis of five clinical trials. J Am Coll Cardiol 2006;48:21–31. [7] Räber L, Jüni P, Löffel L, Wandel S, Cook S, Wenaweser P, et al. Impact of stent overlap on angiographic and long-term clinical outcome in patients undergoing drug eluting stent implantation. J Am Coll Cardiol 2010;55:1178–88. [8] Finn AV, Kolodgie FD, Harnek J, Guerrero LJ, Acampado E, Tefera K, et al. Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents. Circulation 2005;112:270–8. [9] Kitabata H, Loh JP, Pendyala LK, Badr S, Dvir D, Barbash IM, et al. Safety and efficacy outcomes of overlapping second-generation everolimus-eluting stents versus first generation drug-eluting stents. Am J Cardiol 2013;112:1093–8. [10] O’Sullivan CJ, Stefanini GG, Räber L, Heg D, Taniwaki M, Kalesan B, et al. Impact of stent overlap on long-term clinical outcomes in patients treated with newer generation drug-eluting stents. EuroIntervention 2014;9:1076–84. [11] Farooq V, Vranckx P, Mauri L, Cutlip DE, Belardi J, Silber S, et al. Impact of overlapping newer generation drug-eluting stents on clinical and angiographic outcomes: pooled analysis of five trials from the international Global RESOLUTE Program. Heart 2013;99:626–33. [12] Mori N, Okamoto N, Tanaka A, Yano M, Makino N, Egami Y, et al. Comparison of angiographic and 1-year outcomes between a long single stent and overlapping double stents in patients with newer-generation drug-eluting stents for long narrowings. Am J Cardiol 2016;117:1724–8. [13] Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardised definitions. Circulation 2007;115:2344–51. [14] Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, et al. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005;1:219–27. [15] Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–30. [16] Doi H, Maehara A, Mintz GS, Tsujita K, Kubo T, Castellanos C, et al. Classification and potential mechanisms of intravascular ultrasound patterns of stent fracture. Am J Cardiol 2009;103:818–23. [17] Suh J, Park DW, Lee JY, Jung IH, Lee SW, Kim YH, et al. The relationship and threshold of stent length with regard to risk of stent thrombosis after drug-eluting stent implantation. JACC Cardiovasc Interv 2010;3:383–9. [18] Kedhi E, Stone GW, Kereiakes DJ, Serruys PW, Parise H, Fahy M, et al. Stent thrombosis: insights on outcomes, predictors and impact of dual antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials. Eurointervention 2012;8:599–606. [19] Baber U, Mehran R, Sharma SK, Brar S, Yu J, Suh JW, et al. Impact of the everolimuseluting stent on stent thrombosis: a meta-analysis of 13 randomized trials. J Am Coll Cardiol 2011;58:1569–77. [20] Bouras G, Jhamnani S, Ng VG, Haimi I, Mao V, Deible R, et al. Clinical outcomes after PCI treatment of very long lesions with the XIENCE V everolimus eluting stent; pooled analysis from the SPIRIT and XIENCE V USA prospective multicenter trials. Catheter Cardiovasc Interv 2017;89:984–91. [21] Choi HH, Kim JS, Yoon DH, Hong KS, Kim TH, Kim BK, et al. Favorable neointimal coverage in everolimus-eluting stent at 9 months after stent implantation: comparison with sirolimus-eluting stent using optical coherence tomography. Int J Cardiovasc Imaging 2012;28:491–7. [22] Gutiérrez-Chico JL, van Geuns RJ, Regar E, van der Giessen WJ, Kelbæk H, Saunamäki K, et al. Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial. Eur Heart J 2011;32:2454–63. [23] Hoffmann R, Herrmann G, Silber S, Braun P, Werner GS, Hennen B, et al. IMPact Upon Long Lesion StEnting Study Group. Randomized comparison of success and adverse event rates and cost effectiveness of one long versus two short stents for treatment of long coronary narrowings. Am J Cardiol 2002;90:460–4.
Please cite this article as: H.W. Sim, E.H. Thong, P.H. Loh, et al., Treating very-long coronary artery disease in the contemporary drug eluting stent era: Single long 4..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2020.02.005