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Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center experience
Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center experience Charis Costopoulos a,b, Matthew C. Crowson b, Adam J. Brown a,b, Denise M. Braganza b, Martin R. Bennett a, Stephen P. Hoole b, Nick E.J. West b,⁎ a b
Division of Cardiovascular Medicine, University of Cambridge, UK Department of Interventional Cardiology, Papworth Hospital NHS Trust, UK
a r t i c l e
i n f o
Article history: Received 18 April 2015 Received in revised form 30 July 2015 Accepted 7 August 2015 Available online xxxx Keywords: Bioresorbable vascular scaffold Real-world Clinical outcomes Drug-eluting stent
a b s t r a c t Background: Available data on the use of the ABSORB bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA) in real-world patients is limited. The aim of this study was to assess the mid-term clinical outcomes in a real-world population treated with ABSORB BVS. Methods and materials: We retrospectively evaluated all patients treated with ABSORB at Papworth Hospital, Papworth Everard, UK between July 2012 and July 2014. A total of 108 patients (126 lesions) were identified. Clinical follow-up was performed on all subjects by clinic visit or telephone interview. Results: Most patients were male (91.7%) with a relative high incidence of previous myocardial infarction (MI) (40.7%). Clinical presentation was equally divided between stable angina and acute coronary syndrome (ACS) (51.8% vs. 48.2%, p = 0.59). Of the ACS patients, 26.9% presented with ST-elevation myocardial MI. Intravascular imaging was used in all cases. Predilatation (92.9%) and postdilatation (82.5%) were frequently performed. Major adverse cardiac event (MACE) rates defined as the composite of all-cause death, follow-up MI and target vessel revascularization were 2.5% at 6-month and 4.5% at 1-year. The 1-year target lesion failure rate, defined as the composite of cardiac death, target-vessel MI and target lesion revascularization was 1.9%. There was 1 case of subacute stent thrombosis. Conclusions: The use of ABSORB BVS in real-world patients appears to be associated with good mid-term clinical outcomes when guided by intravascular imaging. Larger studies are required to evaluate further the role of BVS in routine clinical practice and examine how this compares to metallic devices. Summary: Available data on the use of the ABSORB BVS in real-world patients is limited. We retrospectively evaluated all patients treated with ABSORB BVS between July 2012 and July 2014. A total of 108 patients (126 lesions) were identified. Clinical presentation was equally divided between stable angina and acute coronary syndrome (51.8% vs. 48.2%, p = 0.59). Predilatation (92.9%) and postdilatation (82.5%) were frequently performed. Estimated MACE rates at 6-month and 1-year were 2.5% and 4.5% respectively, with a 1-year TLF rate of 1.9%. These results suggest that the use of ABSORB BVS use in the real-world is associated with good mid-term clinical outcomes when guided by intravascular imaging. © 2015 Published by Elsevier Inc.
1. Introduction Bioresorbable vascular scaffolds (BVS) offer a new and exciting option in the percutaneous treatment of coronary artery disease (CAD) as their eventual resorption renders the artery free from a permanent metallic ‘cage’. This allows for normal vasomotor vessel function to be restored while also maintaining access for future coronary artery bypass grafting (CABG) if required [1,2]. Results from clinical trials with the commercially available ABSORB BVS (Abbott Vascular, Santa Clara, CA, USA) have been encouraging with low rates of adverse events at midto long-term follow-up and clinical outcomes comparable to those ⁎ Corresponding author at: Department of Interventional Cardiology, Papworth Hospital, Cambridge, CB23 3RE, United Kingdom. Tel.: +44 1480 364504; fax: +44 1480 364799. E-mail address: [email protected] (N.E.J. West).
observed with its metallic counterpart [3]. The role of ABSORB BVS in unselected real-world patients however has not been fully evaluated. Results from small studies suggest that ABSORB BVS can be used in a range of patients including those with ST-segment elevation myocardial infarction (MI), long diffuse disease and in those requiring 2-stent strategies for complex bifurcation disease with good results in the shortterm [4–6]. The aim of this study was to assess mid-term clinical outcomes of ABSORB BVS in a real-world population treated at a singlecenter in the United Kingdom where use of ABSORB is limited. 2. Materials and methods We examined all BVS ABSORB procedures performed at Papworth Hospital, Papworth Everard, UK between July 2012 and July 2014. Each procedure was entered into a percutaneous coronary intervention
http://dx.doi.org/10.1016/j.carrev.2015.08.003 1553-8389/© 2015 Published by Elsevier Inc.
Please cite this article as: Costopoulos C, et al, Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center expe..., Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.08.003
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C. Costopoulos et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
(PCI) database at the time of the procedure and subsequently all clinical parameters were verified by inspecting the case records. Using these criteria, 108 consecutive patients with 126 lesions treated with ABSORB BVS were identified. Over the same interval 3847 patients were treated with metallic stents of which 75.8% received drugeluting stents (DES). The decision to implant ABSORB was largely at the operators’ discretion although this was guided by local guidelines. In general ABSORB implantation was avoided, in patients older than 80 years of age, where concerns regarding the tolerability of 12 month dual antiplatelet therapy (DAPT) were present. Finally, it was mandatory for all operators to receive formal training on the recommended implantation technique for ABSORB prior to incorporating the device to their PCI practice. All patients provided informed consent for both the procedure and subsequent data collection and analysis. Intracoronary imaging, either optical coherence tomography (OCT, DragonFly C7, St. Jude Medical, Saint Paul, USA) or intravascular ultrasound (IVUS, Boston Scientific, Natick, USA), was performed both prior and post scaffold implantation to assess target and lesion vessel characteristics as well as BVS expansion and apposition. With regard to predilatation and postdilatation, these were routinely performed except in patients presenting with STsegment elevation MI. In these cases, postdilatation was only performed when scaffold underexpansion or strut malapposition was present on intravascular imaging in order to minimize the risks of distal embolization. If OCT suggested the presence of a large entry or exit dissection at the scaffold implantation site a further BVS was implanted. All patients received DAPT (aspirin and clopidogrel) for 12 months and aspirin alone thereafter. Clinical follow-up was performed on all subjects by clinic visit or telephone interview. Clinical outcomes reported represent patientspecific data unless otherwise stated. Clinical device success was defined as successful delivery and deployment of stent or scaffold at the target lesion and successful withdrawal of the delivery system with attainment of a final residual stenosis of b30%. Procedural success was defined as clinical device success without the occurrence of ischemia driven major adverse cardiac events (MACE) during the hospital stay with a maximum of the first seven days after the index procedure. MACE was defined as the composite of all-cause death, follow-up MI and target vessel revascularization (TVR). Death was considered cardiac in origin unless obvious non-cardiac causes were identified. MI definitions were in accordance with the most recent universal definition of MI [7]. TVR was defined as repeat PCI or coronary artery bypass graft (CABG) in the target vessel. Target lesion revascularization (TLR) was defined as repeat PCI or CABG for the lesion in the previously treated segment or in the adjacent 5 mm. Target lesion failure (TLF) was defined as the composite of cardiac death, target-vessel MI and TLR. The occurrence of stent thrombosis (ST) was defined on the basis of the Academic Research Consortium definition [8]. Values are presented as mean ± standard deviation (SD) for continuous variables or as counts and percentages for categorical variables. Continuous variables were compared by the independent sample t or Mann–Whitney U tests. Categorical variables were compared by the Chi-square statistic or Fisher’s exact test. A p-value of b0.05 was considered to be statistically significant and all reported p-values are twosided. Time-to-event curves were generated using the Kaplan–Meier method. Analyses were carried out using SPSS for Windows, version 19.0 (SPSS Inc., Chicago, Illinois). 3. Results ABSORB was implanted successfully in 99.1% (n = 109) of patients where this was intended to be used. The 1 case of device failure occurred with a 3.5 × 18 mm scaffold, which could not be delivered in the distal right coronary artery due to excessive tortuosity and significant calcification despite the use of the ‘buddy wire’ and ‘mother-inchild’ techniques. Procedural success rate was also 99.1%. Baseline
clinical characteristics of the patients treated with ABSORB are summarized in Table 1. The majority of treated patients were male (91.7%) with a relatively high incidence of previous MI (40.7%). Clinical presentation was equally divided between stable angina and acute coronary syndrome (ACS) (51.8% vs. 48.2%, p = 0.59). Of the ACS patients, 26.9% presented with ST-elevation MI. Procedural characteristics are shown in Table 2. Most cases were performed via the radial route (92.6%) with the left anterior descending (LAD) artery being the vessel most commonly treated (56.3%). A significant percentage (34.9%) of lesions treated was classified as calcified on the basis of fluoroscopic or intravascular imaging findings and 18.3% involved a bifurcation (Fig. 1). Intravascular imaging was performed in all patients prior and post-BVS implantation with OCT being the modality most commonly utilized (97.6%). Predilatation was routinely performed (92.9%) with a balloon of similar diameter, albeit slightly smaller, to that of the subsequent implanted BVS (2.9 vs. 3.1 mm, p b 0.01). 1:1 balloon:vessel diameter predilatation was utilized in 51.6% of the cases. Overlapping BVS (Fig. 2) was implanted in 22.0% of patients to treat diffuse disease (N 20 mm). Postdilatation was also frequently performed (82.5%) and often with a bigger diameter balloon to that of the implanted BVS. This however did, not exceed the scaffold’s 0.5 mm postdilatation potential (3.4 vs. 3.1 mm, p b 0.01) as per manufacturer’s guidelines. Clinical outcomes are summarized in Table 3. Median follow-up was 326 days (interquartile range (IQ): 258–529 days) with 48% of patients achieving 1-year follow-up. The incidence of MACE and TLF over the entire follow-up period was 5.5% and 2.8% respectively, with 1 reported cardiac death resulting from subacute ST. This occurred in a right coronary artery treated with a 2.5 × 18 mm BVS, 7 days after implantation in a patient with diabetes who initially presented with an ACS. OCT before and after scaffold implantation was performed at the index case and DAPT was not interrupted between then and readmission. Estimated MACE rates at 6-month and 1-year were 2.5% and 4.5% respectively (Fig. 3). TLF at 1-year was 1.9%. There was only 1 case of TLR in a patient treated with a 3.0 × 18 mm BVS who required further treatment within 5 mm of the previously implanted BVS for symptomatic residual disease. 4. Discussion The findings of this study suggest that the use of ABSORB BVS in a real-world population is associated with good clinical outcomes at mid-term follow-up when guided by intravascular imaging. Although these results are promising, larger studies with long-term follow-up are required in order to fully assess the role of these novel devices in the treatment of CAD in the real-world. BVS offers the potential of revolutionizing the percutaneous treatment of CAD since unlike currently available DES, they do not remain in the vessel wall after their intended function of preventing acute recoil and limiting intimal hyperplasia is fulfilled [9,10]. This can lead to further improvements in clinical outcomes as the chronic inflammatory Table 1 Patient Characteristics. Characteristic
Patients (n = 108)
Age, years Male Hypertension Hypercholesterolemia Current smoker Diabetes mellitus Previous myocardial infarction Previous percutaneous coronary intervention Previous coronary artery bypass graft Clinical presentation Stable angina Acute coronary syndrome
58.7 ± 10.5 99 (91.7) 38 (35.1) 56 (51.8) 39 (36.1) 18 (13.9) 44 (40.7) 41 (37.9) 2 (1.9) 56 (51.8) 52 (48.2)
Values are presented as n (%) or mean ± SD.
Please cite this article as: Costopoulos C, et al, Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center expe..., Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.08.003
C. Costopoulos et al. / Cardiovascular Revascularization Medicine xxx (2015) xxx–xxx
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Table 2 Lesion and Procedural Characteristics. Characteristic Vessel treated Left Anterior descending artery Left circumflex artery Right coronary artery Saphenous vein graft Calcified lesions Bifurcations Access Radial Femoral Intravascular imaging Intravascular ultrasound Optical coherence tomography Predilatation Maximum predilatation balloon diameter, mm Average scaffold diameter, mm Average scaffold length per lesion, mm Scaffold deployment pressure, atm Postdilatation Maximum postdilatation balloon diameter, mm
Lesions (n = 126) 71 (56.3) 29 (23.0) 24 (19.1) 2 (1.6) 44 (34.9) 23 (18.3) n = 108 100 (92.6) 8 (7.4) 3 (2.4) 123 (97.6) 117 (92.9) 2.9 ± 0.4 3.1 ± 0.4 27.0 ± 9.5 15.0 ± 1.8 104 (82.5) 3.4 ± 0.4
Values are presented as n (%) or mean ± SD.
stimulus of metallic struts and polymers, which has been linked to restenosis and very late ST is removed [11]. Initial clinical trials with ABSORB BVS reported good patient outcomes at mid- to long-term follow-up with more studies currently underway examining the role of these devices in routine clinical practice. The ABSORB EXTEND (ABSORB EXTEND Clinical Investigation: A Continuation in the Clinical Evaluation of the ABSORB Bioresorbable Vascular Scaffold (BVS) System in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) study, which included patients with small vessel (≥2.0 mm) as well as diffuse (≤28 mm) disease has recently reported the 1-year results from the first 512 enrolled patients. Ischemia-driven MACE and target vessel failure rates in this cohort were encouraging at 4.3% and 4.6%, respectively [12]. The incidence of probable or definite ST over the same interval was 0.8%. Despite these encouraging results the patients recruited in ABSORB EXTEND do not necessarily represent the ‘real-world’ as the presence of visible thrombus or ≥2.0 mm side branch vessels at the culprit site formed part of the exclusion criteria. The GHOST-EU registry on other hand, which included 1189 better reflected
Fig. 2. OCT image of 2 overlapping BVS in a right coronary artery demonstrating good luminal area.
contemporary PCI practice, as patients with any coronary artery lesions suitable for stenting were included in this analysis. Despite acceptable TLF rates at 6-month and 1-year (4.4% and 10.1%), ST rates at 30-day (1.5%) and 6-month were relatively high (1.5% and 2.1%). These results are in contrast with the ones observed in our study where TLF and ST rates over the same intervals were 1.9% and 0.9%, respectively. Although a number of reasons may be responsible for this, including differences in disease complexity, it is possible that the more liberal use of intravascular imaging (100% vs. 28.2%) and postdilatation in our study (82.5% vs. 49.8%) has impacted positively on clinical outcomes through more accurate device sizing, improved scaffold expansion and reduced strut malapposition. Our findings in fact, are more in keeping with those observed from ‘real-world’ multi-center randomized trials with contemporary metallic DES. In the large, randomized COMPARE II (Comparison of the Everolimus Eluting With the Biolimus A9 Eluting Stent) trial, TLF rates at 1-year for the widely used everolimus-eluting (EES) and biodegradable polymer biolimus-eluting stents were 3.7% and 4.2%, respectively [13]. The RESOLUTE All Comers (A Randomized Comparison of a Zotarolimus-Eluting Stent With an EverolimusEluting Stent for Percutaneous Coronary Intervention) trial on the other hand reported a 6-month TLF rate of 6.5% for EES and 6.3% for the zotarolimus-eluting stent [14]. This suggests that BVS may be able
Table 3 Clinical Outcomes.
Fig. 1. OCT image of a BVS across the left anterior descending/first diagonal bifurcation with no evidence of compromise of the side-branch ostium.
Outcome
Patients (n = 108)
MACEa All-cause death Cardiac death Non-cardiac death Follow-up MI Treated vessel MI TVR TLR TLFb Definite or probable ST
6 (5.5) 1 (0.9) 1 (0.9) 0 5 (4.6) 2 (1.9) 2 (1.9) 1 (0.9) 3 (2.8) 1 (0.9)
MACE = major adverse cardiac events, MI = myocardial infarction, TVR = target vessel revascularization, TLR = target lesion revascularization, TLF = target lesion failure, ST = stent/scaffold thrombosis. a MACE was defined as the composite endpoint of all-cause death, follow-up MI and TVR. b TLF was defined as all-cause death, TLR and target-vessel MI.
Please cite this article as: Costopoulos C, et al, Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center expe..., Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.08.003
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was necessary in view of the absence of large-scale clinical data with BVS in real-world patients. Finally, it is possible that a degree of selection bias may have been present during patient selection for BVS implantation, which may have impacted on our findings. References
Fig. 3. Kaplan–Meier time-to-event curve for MACE.
to replicate the results observed with conventional DES at least when used in conjunction with intravascular imaging and routine postdilatation with the added advantage of restoring treated vessels to a more ‘normal’ state following resorption. In conclusion our results suggest that the use of ABSORB BVS in a realworld population is associated with good mid-term outcomes similar to those reported for conventional metallic stents. It is important to emphasize that these results were obtained after meticulous lesion preparation, accurate scaffold sizing and intracoronary imaging guided postdilatation for adequate scaffold expansion. Such an approach may represent optimal practice for the implantation of these devices. The ABSORB III and IV studies (A Clinical Evaluation of Absorb™ BVS, the Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) currently recruiting will provide more robust evidence on the role of BVS in the real-world as well as an indication as to whether these devices can improve PCI outcomes. Limitations to our study include its retrospective design, relatively short follow-up period and absence of a control group. The extensive use of intravascular imaging can also be considered as a limitation as this does not necessarily form part of contemporary PCI practice and may have positively affected on our results. We felt however that this
[1] Serruys PW, Onuma Y, Dudek D, Smits PC, Koolen J, Chevalier B, et al. Evaluation of the second generation of a bioresorbable everolimus-eluting vascular scaffold for the treatment of de novo coronary artery stenosis: 12-month clinical and imaging outcomes. J Am Coll Cardiol 2011;58(15):1578–88. [2] Serruys PW, Onuma Y, Garcia-Garcia HM, Muramatsu T, van Geuns RJ, de Bruyne B, et al. Dynamics of vessel wall changes following the implantation of the absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. EuroIntervention 2014;9(11):1271–84. [3] Serruys PW, Chevalier B, Dudek D, Cequier A, Carrie D, Iniguez A, et al. A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial. Lancet 2015;385(9962):43–54. [4] Costopoulos C, Latib A, Naganuma T, Miyazaki T, Sato K, Figini F, et al. Comparison of early clinical outcomes between absorb bioresorbable vascular scaffold and everolimus-eluting stent implantation in a real-world population. Catheter Cardiovasc Interv 2015;85(1):E10–5. [5] Ielasi A, Cortese B, Varricchio A, Tespili M, Sesana M, Pisano F, et al. Immediate and midterm outcomes following primary PCI with bioresorbable vascular scaffold implantation in patients with ST-segment myocardial infarction: insights from the multicentre “Registro ABSORB Italiano” (RAI registry). EuroIntervention 2015; 11(2):157–62. [6] Costopoulos C, Naganuma T, Latib A, Colombo A. Optical coherence tomography of a bifurcation lesion treated with bioresorbable vascular scaffolds with the “minicrush” technique. J Am Coll Cardiol Intv 2013;6(12):1326–7. [7] Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Circulation 2012;126(16):2020–35. [8] Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115(17):2344–51. [9] Latib A, Costopoulos C, Naganuma T, Colombo A. Which patients could benefit the most from bioresorbable vascular scaffold implant: from clinical trials to clinical practice. Minerva Cardioangiol 2013;61(3):255–62. [10] Costopoulos C, Naganuma T, Latib A, Colombo A. Looking into the future with bioresorbable vascular scaffolds. Expert Rev Cardiovasc Ther 2013;11(10):1407–16. [11] Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, et al. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol 2011;57(11):1314–22. [12] Abizaid A, Costa JR, Bartorelli AL, Whitbourn R, van Geuns RJ, Chevalier B, et al. The ABSORB EXTEND study: preliminary report of the twelve-month clinical outcomes in the first 512 patients enrolled. EuroIntervention 2015;10(12): 1396–401. [13] Smits PC, Hofma S, Togni M, Vazquez N, Valdes M, Slagboom T, et al. Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimuseluting stent (COMPARE II): a randomised, controlled, non-inferiority trial. Lancet 2013;381(9867):651–60. [14] Serruys PW, Silber S, Garg S, van Geuns RJ, Richardt G, Buszman PE, et al. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med 2010;363(2):136–46.
Please cite this article as: Costopoulos C, et al, Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center expe..., Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.08.003
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center experience Charis Costopoulos a,b, Matthew C. Crowson b, Adam J. Brown a,b, Denise M. Braganza b, Martin R. Bennett a, Stephen P. Hoole b, Nick E.J. West b,⁎ a b
Division of Cardiovascular Medicine, University of Cambridge, UK Department of Interventional Cardiology, Papworth Hospital NHS Trust, UK
a r t i c l e
i n f o
Article history: Received 18 April 2015 Received in revised form 30 July 2015 Accepted 7 August 2015 Available online xxxx Keywords: Bioresorbable vascular scaffold Real-world Clinical outcomes Drug-eluting stent
a b s t r a c t Background: Available data on the use of the ABSORB bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA) in real-world patients is limited. The aim of this study was to assess the mid-term clinical outcomes in a real-world population treated with ABSORB BVS. Methods and materials: We retrospectively evaluated all patients treated with ABSORB at Papworth Hospital, Papworth Everard, UK between July 2012 and July 2014. A total of 108 patients (126 lesions) were identified. Clinical follow-up was performed on all subjects by clinic visit or telephone interview. Results: Most patients were male (91.7%) with a relative high incidence of previous myocardial infarction (MI) (40.7%). Clinical presentation was equally divided between stable angina and acute coronary syndrome (ACS) (51.8% vs. 48.2%, p = 0.59). Of the ACS patients, 26.9% presented with ST-elevation myocardial MI. Intravascular imaging was used in all cases. Predilatation (92.9%) and postdilatation (82.5%) were frequently performed. Major adverse cardiac event (MACE) rates defined as the composite of all-cause death, follow-up MI and target vessel revascularization were 2.5% at 6-month and 4.5% at 1-year. The 1-year target lesion failure rate, defined as the composite of cardiac death, target-vessel MI and target lesion revascularization was 1.9%. There was 1 case of subacute stent thrombosis. Conclusions: The use of ABSORB BVS in real-world patients appears to be associated with good mid-term clinical outcomes when guided by intravascular imaging. Larger studies are required to evaluate further the role of BVS in routine clinical practice and examine how this compares to metallic devices. Summary: Available data on the use of the ABSORB BVS in real-world patients is limited. We retrospectively evaluated all patients treated with ABSORB BVS between July 2012 and July 2014. A total of 108 patients (126 lesions) were identified. Clinical presentation was equally divided between stable angina and acute coronary syndrome (51.8% vs. 48.2%, p = 0.59). Predilatation (92.9%) and postdilatation (82.5%) were frequently performed. Estimated MACE rates at 6-month and 1-year were 2.5% and 4.5% respectively, with a 1-year TLF rate of 1.9%. These results suggest that the use of ABSORB BVS use in the real-world is associated with good mid-term clinical outcomes when guided by intravascular imaging. © 2015 Published by Elsevier Inc.
1. Introduction Bioresorbable vascular scaffolds (BVS) offer a new and exciting option in the percutaneous treatment of coronary artery disease (CAD) as their eventual resorption renders the artery free from a permanent metallic ‘cage’. This allows for normal vasomotor vessel function to be restored while also maintaining access for future coronary artery bypass grafting (CABG) if required [1,2]. Results from clinical trials with the commercially available ABSORB BVS (Abbott Vascular, Santa Clara, CA, USA) have been encouraging with low rates of adverse events at midto long-term follow-up and clinical outcomes comparable to those ⁎ Corresponding author at: Department of Interventional Cardiology, Papworth Hospital, Cambridge, CB23 3RE, United Kingdom. Tel.: +44 1480 364504; fax: +44 1480 364799. E-mail address: [email protected] (N.E.J. West).
observed with its metallic counterpart [3]. The role of ABSORB BVS in unselected real-world patients however has not been fully evaluated. Results from small studies suggest that ABSORB BVS can be used in a range of patients including those with ST-segment elevation myocardial infarction (MI), long diffuse disease and in those requiring 2-stent strategies for complex bifurcation disease with good results in the shortterm [4–6]. The aim of this study was to assess mid-term clinical outcomes of ABSORB BVS in a real-world population treated at a singlecenter in the United Kingdom where use of ABSORB is limited. 2. Materials and methods We examined all BVS ABSORB procedures performed at Papworth Hospital, Papworth Everard, UK between July 2012 and July 2014. Each procedure was entered into a percutaneous coronary intervention
http://dx.doi.org/10.1016/j.carrev.2015.08.003 1553-8389/© 2015 Published by Elsevier Inc.
Please cite this article as: Costopoulos C, et al, Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center expe..., Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.08.003
2
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(PCI) database at the time of the procedure and subsequently all clinical parameters were verified by inspecting the case records. Using these criteria, 108 consecutive patients with 126 lesions treated with ABSORB BVS were identified. Over the same interval 3847 patients were treated with metallic stents of which 75.8% received drugeluting stents (DES). The decision to implant ABSORB was largely at the operators’ discretion although this was guided by local guidelines. In general ABSORB implantation was avoided, in patients older than 80 years of age, where concerns regarding the tolerability of 12 month dual antiplatelet therapy (DAPT) were present. Finally, it was mandatory for all operators to receive formal training on the recommended implantation technique for ABSORB prior to incorporating the device to their PCI practice. All patients provided informed consent for both the procedure and subsequent data collection and analysis. Intracoronary imaging, either optical coherence tomography (OCT, DragonFly C7, St. Jude Medical, Saint Paul, USA) or intravascular ultrasound (IVUS, Boston Scientific, Natick, USA), was performed both prior and post scaffold implantation to assess target and lesion vessel characteristics as well as BVS expansion and apposition. With regard to predilatation and postdilatation, these were routinely performed except in patients presenting with STsegment elevation MI. In these cases, postdilatation was only performed when scaffold underexpansion or strut malapposition was present on intravascular imaging in order to minimize the risks of distal embolization. If OCT suggested the presence of a large entry or exit dissection at the scaffold implantation site a further BVS was implanted. All patients received DAPT (aspirin and clopidogrel) for 12 months and aspirin alone thereafter. Clinical follow-up was performed on all subjects by clinic visit or telephone interview. Clinical outcomes reported represent patientspecific data unless otherwise stated. Clinical device success was defined as successful delivery and deployment of stent or scaffold at the target lesion and successful withdrawal of the delivery system with attainment of a final residual stenosis of b30%. Procedural success was defined as clinical device success without the occurrence of ischemia driven major adverse cardiac events (MACE) during the hospital stay with a maximum of the first seven days after the index procedure. MACE was defined as the composite of all-cause death, follow-up MI and target vessel revascularization (TVR). Death was considered cardiac in origin unless obvious non-cardiac causes were identified. MI definitions were in accordance with the most recent universal definition of MI [7]. TVR was defined as repeat PCI or coronary artery bypass graft (CABG) in the target vessel. Target lesion revascularization (TLR) was defined as repeat PCI or CABG for the lesion in the previously treated segment or in the adjacent 5 mm. Target lesion failure (TLF) was defined as the composite of cardiac death, target-vessel MI and TLR. The occurrence of stent thrombosis (ST) was defined on the basis of the Academic Research Consortium definition [8]. Values are presented as mean ± standard deviation (SD) for continuous variables or as counts and percentages for categorical variables. Continuous variables were compared by the independent sample t or Mann–Whitney U tests. Categorical variables were compared by the Chi-square statistic or Fisher’s exact test. A p-value of b0.05 was considered to be statistically significant and all reported p-values are twosided. Time-to-event curves were generated using the Kaplan–Meier method. Analyses were carried out using SPSS for Windows, version 19.0 (SPSS Inc., Chicago, Illinois). 3. Results ABSORB was implanted successfully in 99.1% (n = 109) of patients where this was intended to be used. The 1 case of device failure occurred with a 3.5 × 18 mm scaffold, which could not be delivered in the distal right coronary artery due to excessive tortuosity and significant calcification despite the use of the ‘buddy wire’ and ‘mother-inchild’ techniques. Procedural success rate was also 99.1%. Baseline
clinical characteristics of the patients treated with ABSORB are summarized in Table 1. The majority of treated patients were male (91.7%) with a relatively high incidence of previous MI (40.7%). Clinical presentation was equally divided between stable angina and acute coronary syndrome (ACS) (51.8% vs. 48.2%, p = 0.59). Of the ACS patients, 26.9% presented with ST-elevation MI. Procedural characteristics are shown in Table 2. Most cases were performed via the radial route (92.6%) with the left anterior descending (LAD) artery being the vessel most commonly treated (56.3%). A significant percentage (34.9%) of lesions treated was classified as calcified on the basis of fluoroscopic or intravascular imaging findings and 18.3% involved a bifurcation (Fig. 1). Intravascular imaging was performed in all patients prior and post-BVS implantation with OCT being the modality most commonly utilized (97.6%). Predilatation was routinely performed (92.9%) with a balloon of similar diameter, albeit slightly smaller, to that of the subsequent implanted BVS (2.9 vs. 3.1 mm, p b 0.01). 1:1 balloon:vessel diameter predilatation was utilized in 51.6% of the cases. Overlapping BVS (Fig. 2) was implanted in 22.0% of patients to treat diffuse disease (N 20 mm). Postdilatation was also frequently performed (82.5%) and often with a bigger diameter balloon to that of the implanted BVS. This however did, not exceed the scaffold’s 0.5 mm postdilatation potential (3.4 vs. 3.1 mm, p b 0.01) as per manufacturer’s guidelines. Clinical outcomes are summarized in Table 3. Median follow-up was 326 days (interquartile range (IQ): 258–529 days) with 48% of patients achieving 1-year follow-up. The incidence of MACE and TLF over the entire follow-up period was 5.5% and 2.8% respectively, with 1 reported cardiac death resulting from subacute ST. This occurred in a right coronary artery treated with a 2.5 × 18 mm BVS, 7 days after implantation in a patient with diabetes who initially presented with an ACS. OCT before and after scaffold implantation was performed at the index case and DAPT was not interrupted between then and readmission. Estimated MACE rates at 6-month and 1-year were 2.5% and 4.5% respectively (Fig. 3). TLF at 1-year was 1.9%. There was only 1 case of TLR in a patient treated with a 3.0 × 18 mm BVS who required further treatment within 5 mm of the previously implanted BVS for symptomatic residual disease. 4. Discussion The findings of this study suggest that the use of ABSORB BVS in a real-world population is associated with good clinical outcomes at mid-term follow-up when guided by intravascular imaging. Although these results are promising, larger studies with long-term follow-up are required in order to fully assess the role of these novel devices in the treatment of CAD in the real-world. BVS offers the potential of revolutionizing the percutaneous treatment of CAD since unlike currently available DES, they do not remain in the vessel wall after their intended function of preventing acute recoil and limiting intimal hyperplasia is fulfilled [9,10]. This can lead to further improvements in clinical outcomes as the chronic inflammatory Table 1 Patient Characteristics. Characteristic
Patients (n = 108)
Age, years Male Hypertension Hypercholesterolemia Current smoker Diabetes mellitus Previous myocardial infarction Previous percutaneous coronary intervention Previous coronary artery bypass graft Clinical presentation Stable angina Acute coronary syndrome
58.7 ± 10.5 99 (91.7) 38 (35.1) 56 (51.8) 39 (36.1) 18 (13.9) 44 (40.7) 41 (37.9) 2 (1.9) 56 (51.8) 52 (48.2)
Values are presented as n (%) or mean ± SD.
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Table 2 Lesion and Procedural Characteristics. Characteristic Vessel treated Left Anterior descending artery Left circumflex artery Right coronary artery Saphenous vein graft Calcified lesions Bifurcations Access Radial Femoral Intravascular imaging Intravascular ultrasound Optical coherence tomography Predilatation Maximum predilatation balloon diameter, mm Average scaffold diameter, mm Average scaffold length per lesion, mm Scaffold deployment pressure, atm Postdilatation Maximum postdilatation balloon diameter, mm
Lesions (n = 126) 71 (56.3) 29 (23.0) 24 (19.1) 2 (1.6) 44 (34.9) 23 (18.3) n = 108 100 (92.6) 8 (7.4) 3 (2.4) 123 (97.6) 117 (92.9) 2.9 ± 0.4 3.1 ± 0.4 27.0 ± 9.5 15.0 ± 1.8 104 (82.5) 3.4 ± 0.4
Values are presented as n (%) or mean ± SD.
stimulus of metallic struts and polymers, which has been linked to restenosis and very late ST is removed [11]. Initial clinical trials with ABSORB BVS reported good patient outcomes at mid- to long-term follow-up with more studies currently underway examining the role of these devices in routine clinical practice. The ABSORB EXTEND (ABSORB EXTEND Clinical Investigation: A Continuation in the Clinical Evaluation of the ABSORB Bioresorbable Vascular Scaffold (BVS) System in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) study, which included patients with small vessel (≥2.0 mm) as well as diffuse (≤28 mm) disease has recently reported the 1-year results from the first 512 enrolled patients. Ischemia-driven MACE and target vessel failure rates in this cohort were encouraging at 4.3% and 4.6%, respectively [12]. The incidence of probable or definite ST over the same interval was 0.8%. Despite these encouraging results the patients recruited in ABSORB EXTEND do not necessarily represent the ‘real-world’ as the presence of visible thrombus or ≥2.0 mm side branch vessels at the culprit site formed part of the exclusion criteria. The GHOST-EU registry on other hand, which included 1189 better reflected
Fig. 2. OCT image of 2 overlapping BVS in a right coronary artery demonstrating good luminal area.
contemporary PCI practice, as patients with any coronary artery lesions suitable for stenting were included in this analysis. Despite acceptable TLF rates at 6-month and 1-year (4.4% and 10.1%), ST rates at 30-day (1.5%) and 6-month were relatively high (1.5% and 2.1%). These results are in contrast with the ones observed in our study where TLF and ST rates over the same intervals were 1.9% and 0.9%, respectively. Although a number of reasons may be responsible for this, including differences in disease complexity, it is possible that the more liberal use of intravascular imaging (100% vs. 28.2%) and postdilatation in our study (82.5% vs. 49.8%) has impacted positively on clinical outcomes through more accurate device sizing, improved scaffold expansion and reduced strut malapposition. Our findings in fact, are more in keeping with those observed from ‘real-world’ multi-center randomized trials with contemporary metallic DES. In the large, randomized COMPARE II (Comparison of the Everolimus Eluting With the Biolimus A9 Eluting Stent) trial, TLF rates at 1-year for the widely used everolimus-eluting (EES) and biodegradable polymer biolimus-eluting stents were 3.7% and 4.2%, respectively [13]. The RESOLUTE All Comers (A Randomized Comparison of a Zotarolimus-Eluting Stent With an EverolimusEluting Stent for Percutaneous Coronary Intervention) trial on the other hand reported a 6-month TLF rate of 6.5% for EES and 6.3% for the zotarolimus-eluting stent [14]. This suggests that BVS may be able
Table 3 Clinical Outcomes.
Fig. 1. OCT image of a BVS across the left anterior descending/first diagonal bifurcation with no evidence of compromise of the side-branch ostium.
Outcome
Patients (n = 108)
MACEa All-cause death Cardiac death Non-cardiac death Follow-up MI Treated vessel MI TVR TLR TLFb Definite or probable ST
6 (5.5) 1 (0.9) 1 (0.9) 0 5 (4.6) 2 (1.9) 2 (1.9) 1 (0.9) 3 (2.8) 1 (0.9)
MACE = major adverse cardiac events, MI = myocardial infarction, TVR = target vessel revascularization, TLR = target lesion revascularization, TLF = target lesion failure, ST = stent/scaffold thrombosis. a MACE was defined as the composite endpoint of all-cause death, follow-up MI and TVR. b TLF was defined as all-cause death, TLR and target-vessel MI.
Please cite this article as: Costopoulos C, et al, Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center expe..., Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.08.003
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was necessary in view of the absence of large-scale clinical data with BVS in real-world patients. Finally, it is possible that a degree of selection bias may have been present during patient selection for BVS implantation, which may have impacted on our findings. References
Fig. 3. Kaplan–Meier time-to-event curve for MACE.
to replicate the results observed with conventional DES at least when used in conjunction with intravascular imaging and routine postdilatation with the added advantage of restoring treated vessels to a more ‘normal’ state following resorption. In conclusion our results suggest that the use of ABSORB BVS in a realworld population is associated with good mid-term outcomes similar to those reported for conventional metallic stents. It is important to emphasize that these results were obtained after meticulous lesion preparation, accurate scaffold sizing and intracoronary imaging guided postdilatation for adequate scaffold expansion. Such an approach may represent optimal practice for the implantation of these devices. The ABSORB III and IV studies (A Clinical Evaluation of Absorb™ BVS, the Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) currently recruiting will provide more robust evidence on the role of BVS in the real-world as well as an indication as to whether these devices can improve PCI outcomes. Limitations to our study include its retrospective design, relatively short follow-up period and absence of a control group. The extensive use of intravascular imaging can also be considered as a limitation as this does not necessarily form part of contemporary PCI practice and may have positively affected on our results. We felt however that this
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Please cite this article as: Costopoulos C, et al, Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation in a real-world population: A single-center expe..., Cardiovasc Revasc Med (2015), http://dx.doi.org/10.1016/j.carrev.2015.08.003