- Email: [email protected]
Clinical Comparison With Short-Term Follow-Up of Bioresorbable Vascular Scaffold Versus Everolimus-Eluting Stent in Primary Percutaneous Coronary Interventions
Clinical Comparison With Short-Term Follow-Up of Bioresorbable Vascular Scaffold Versus Everolimus-Eluting Stent in Primary Percutaneous Coronary Interventions Bernardo Cortese, MDa,*, Alfonso Ielasi, MDb, Enrico Romagnoli, MDc, Attilio Varricchio, MD, PhDd, Andrea Cuculo, MDe, Bruno Loi, MDf, Francesco Pisano, MDg, Donatella Corrado, MDh, Marco Sesana, MDi, Luigi La Vecchia, MDj, Francesco Summaria, MDk, Maurizio Tespili, MDb, Pedro Silva Orrego, MDa, Gianni Tognoni, MDh, and Giuseppe Steffenino, MDl Objective of this study was to assess the clinical performance of bioresorbable vascular scaffold (BVS) compared to everolimus-eluting stent (EES) in subjects with ST-segment elevation myocardial infarction (STEMI). We included all consecutive patients with STEMI who underwent percutaneous coronary intervention (PCI) with BVS implantation in centers participating to the Italian ABSORB Prospective Registry (BVS-RAI) and PCI with EES in the same centers during the same period. The 2 groups were compared. The primary end point was patient-oriented composite end point (POCE) including cardiac death, myocardial infarction, and target lesion revascularization (TLR) at the longest available follow-up. BVS or EES thrombosis at follow-up was also evaluated. Of the 563 patients with STEMI included, 122 received BVS and 441 EES. Procedural success was obtained in 549 (97.5%) cases without significant differences between the 2 groups (BVS 99.3% vs EES 97.0%, p [ 0.2). At a median of 220-day (interquartile range 178 to 369) follow-up, no significant differences were observed in terms of POCE (BVS 4.9% vs EES 7.0%, p [ 0.4); death (BVS 0.8%, EES 2.0%, p [ 0.4), MI (BVS 4.1%, EES 2.0%, p [ 0.2), TLR (BVS 4.1%, EES 4.5%, p [ 0.8), device thrombosis (BVS 2.5%, EES 1.4%, p [ 0.4). All TLR cases were successfully managed with re-PCI in both groups. A propensity matching of the study populations showed no significant differences regarding POCE at the longest available follow-up (odds ratio 0.53, 0.1 to 4.3). In conclusion, in this direct prospective comparison, BVS was associated with similar clinical results compared to EES in the STEMI setting. Larger and adequately powered randomized trials are needed to fully assess the potential clinical benefit of BVS versus the current standard of care in patients with STEMI. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;-:-e-) Mechanical reperfusion of epicardial coronary arteries by primary percutaneous coronary intervention (PPCI) is currently the treatment of choice in patients with ST-segment elevation myocardial infarction (STEMI).1 Advances in
a Department of Interventional Cardiology, A.O. Fatebenefratelli, Milano, Italy; bDepartment of Cardiology, A.O. Bolognini, Seriate, Italy; c Department of Cardiology, A.O. Belcolle, Viterbo, Italy; dDepartment of Cardiology, Ospedale Monaldi, Napoli, Italy; eDepartment of Cardiology, A.O. Ospedali Riuniti, Foggia, Italy; fDepartment of Interventional Cardiology, A.O. Brotzu, Cagliari, Italy; gDepartment of Interventional Cardiology, Ospedale Regionale Parini, Aosta, Italy; hCentro di Ricerche Farmacologiche e Biomediche “Mario Negri”, Milano, Italy; iDepartment of Interventional Cardiology, A.O. Desenzano del Garda, Desenzano del Garda, Italy; jDepartment of Interventional Cardiology, Ospedale San Bortolo, Vicenza, Italy; kDepartment of Interventional Cardiology, Policlinico Casilino, Roma, Italy; and lDepartment of Interventional Cardiology, A.O. S.Croce e Carle, Cuneo, Italy. Manuscript received March 18, 2015; revised manuscript received and accepted May 20, 2015. Drs. Cortese and Ielasi equally contributed to the manuscript. See page 6 for disclosure information. *Corresponding author: Tel/fax: (þ39) 0263632210. E-mail address: [email protected] (B. Cortese).
0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.05.049
interventional techniques, administration of more potent antiplatelet drugs, and the evolution from bare metal stents (BMS) to drug-eluting stents (DES) have improved the outcomes of patients with STEMI.2e4 In particular, the cobaltechromium (Co-Cr) everolimus-eluting stent (EESXience; Abbott Vascular, California) has been shown to have a very favorable safety and efficacy profile and may be considered the standard of care for the treatment of patients with STEMI.5,6 Even if the current stent-based reperfusion strategies are associated with a high clinical performance, they have shortcomings related to the durable caging of the coronary wall. Indeed, the implantation of a permanent intracoronary metallic prosthesis may be associated to stent thrombosis (ST), restenosis, and malapposition. To overcome these limitations, new technologies are under investigation in the STEMI setting.7 The ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS, Abbott Vascular) is an intracoronary prosthesis that provides temporary scaffolding and, over a period of 3 years, is fully reabsorbed by biochemical reactions, thus restoring the native pristine vessel state.8,9 The objective of this study was to assess the clinical performance of BVS compared to EES in subjects with STEMI who underwent PPCI. www.ajconline.org
2
The American Journal of Cardiology (www.ajconline.org)
Table 1 Baseline clinical characteristics (patient basis) Variable Age (years)* Women Hypertension Hypercholesterolemia Smoker Family history of CAD Diabetes mellitus Insulin dependent Non-insulin dependent Prior myocardial infarction Prior revascularization Prior percutaneous coronary intervention Prior coronary bypass Peripheral artery disease Multivessel coronary disease Killip class I II III IV Culprit coronary artery Left Anterior Descending Left Circumflex Right
Overall (n¼563) 59 125 327 330 253 173 99 52 47 41 42 39 5 44 278
(52-67) (22.2%) (58.1%) (58.6%) (44.9%) (30.7%) (17.6%) (9.2%) (8.4%) (7.3%) (7.5%) (6.9%) (0.9%) (7.8%) (49.4%)
BVS group (n¼122) 54 31 59 90 60 49 12 5 7 15 13 13 0 1 52
(48-60) (25.4%) (48.4%) (73.8%) (49.2%) (40.2%) (9.8%) (4.1%) (5.7%) (12.3%) (10.7%) (10.7%) (0.0%) (0.8%) (42.6%)
EES group (n¼441) 61 94 268 240 193 124 87 47 40 26 29 26 5 43 226
(53-68) (21.3%) (60.8%) (54.4%) (43.8%) (28.1%) (19.7%) (10.7%) (9.1%) (5.9%) (6.6%) (5.9%) (1.1%) (9.8%) (51.2%)
p
(82.6%) (12.6%) (2.9%) (1.9%)
(91.0%) (8.2%) (0.8%) (0.0%)
(79.9%) (14.0%) (3.6%) (2.5%)
0.001 0.401 0.019 0.001 0.336 0.015 0.016 0.042 0.321 0.027 0.186 0.103 0.525 0.002 0.113 0.026 0.008 0.126 0.206 0.171
334 (59.3%) 75 (13.3%) 154 (27.4%)
74 (60.7%) 16 (13.1%) 32 (26.2%)
260 (59.0%) 59 (13.4%) 122 (27.7%)
0.815 1.000 0.842
Bold values indicate statistically significant differences among groups. BVS ¼ bioresorbable vascular scaffold; Family history of CAD ¼ family history of coronary artery disease; EES ¼ everolimus-eluting stent; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention; CABG ¼ coronary artery by-pass grafting. * Expressed as median and interquartile range.
Methods Aim of this study was to assess the clinical outcomes of consecutive patients with STEMI with symptoms onset <24 hours who underwent PPCI with Absorb-BVS or EES implantation at 11 centers involved in the “Italian ABSORB Registry” (BVS-RAI), a spontaneous, prospective, ongoing multicenter Italian registry without fundings or benefits from the BVS manufacturer (ClinicalTrials.gov identifier is CT02298413). This registry includes all consecutive patients who have successfully undergone unrestricted implantation of 1 BVS. Baseline patient clinical data are entered into a Web-based case report form. The conduct of the registry has been approved by the Ethics Committees of all participating centers. Written informed consent was obtained from all patients to include their data in the database. The registry started in October 2012 and will extend enrollment throughout 2015, with the aims to include 1,000 patients and assess major adverse cardiovascular events (MACE) during a 5-year follow-up. Data on PPCI patients from the BVS-RAI have already been published in part.10 Data from the centers contributing PPCI cases were also collected for all consecutive EES implanted during PPCI in the same time lapse. The full range of sizes and/or lengths for both BVS and EES was available during the study period in all participating centers. Although the decision to implant BVS rather than EES was the operator’s choice, vessel
tortuosity and/or severe calcification proximally to the culprit lesion and infarct artery reference diameter visually exceeding the range of 2.5 to 4 mm were often considered criteria against BVS use. Available lengths for BVS during the study period were 12, 18, and 28 mm. All patients received a loading dose of commonly used antiplatelet drugs periprocedurally. The DAT regimen at discharge consisted in aspirin indefinitely, in association with clopidogrel, ticagrelor, prasugrel for 12 months. Intracoronary imaging, thrombus aspiration, lesion predilatation, and postdilatation (with a maximum diameter of 0.5 mm greater than the BVS diameter) were at the operator’s discretion.10 Primary end points of this study were the cumulative occurrence of POCE (a composite of patient-oriented MACE, including death, MI, target lesion revascularization [TLR]) and device thrombosis at 6-month follow-up. Furthermore, we evaluated procedural success, defined as a final stenosis at the culprit site of <30% with thrombolysis in myocardial infarction 3 flow and without inhospital POCE. Clinical events were defined according to the Academic Research Consortium definitions.11 Furthermore, we differentiated POCE with device-oriented clinical outcome (DOCE). Clinical data were collected by hospital visits at 1 and 6 months. Source verification and queries generation from the coordinating center to the participating sites were undertaken to account partly for the unavoidable bias of site-reported events adjudication. An independent
Coronary Artery Disease/BVS Versus EES in Primary PCI
3
Table 2 Baseline procedural characteristics (lesion basis) Variable Radial approach Treated coronary artery Left Anterior Descending Left Circumflex Right Occluded vessel Stenosis severity* Thrombus score* Thrombectomy use Direct stenting Bifurcational lesions Buddy wire Predilation Predilation balloon diameter (mm)* Stent diameter (mm)* Stent length (mm)* Max pressure during stent implantation† Overlapping stent Post-dilation Postdilation balloon diameter (mm)* Postdilation upsizing (mm) OCT/IVUS guidance Device-related complications Procedural success Final TIMI 3 IIB/IIIA inhibitors administration Bivalirudin Dual antiplatelet therapy ASA þ Clopidogrel ASA þ Ticagrelor/Prasugrel
Overall (n¼605)
BVS group (n¼135)
EES group (n¼ 470)
417 (68.9%)
88 (65.2%)
329 (70.0%)
0.337
275 63 132 280 100 4 247 188 98 27 282 2.5 3.0 23 14 112 178 3.5 0.25 2 23 456 459 176 108
0.715 0.919 0.830 0.001 0.001 0.104 0.616 0.001 0.001 0.009 0.001 0.001 0.009 0.041 0.001 0.699 0.001 0.077 0.221 0.045 0.063 0.246 0.410 0.647 0.001
357 80 168 334 100 4 314 196 103 27 409 2.5 3.0 23 14 147 305 3.5 0.5 8 25 590 593 223 115
(59.0%) (13.2%) (27.8%) (55.2%) (95-100%) (3-5) (51.9%) (32.4%) (17.0%) (4.5%) (67.6%) (2.0-2.5) (2.75-3.5) (18-33) (12-14) (24.3%) (57.7%) (3.0-3.75) (0.0-0.5) (1.3%) (4.1%) (97.5%) (98.0%) (36.9%) (19.0%)
82 17 36 54 99 4 67 8 5 0 127 2.75 3.0 18 10 35 127 3.5 0.5 6 2 134 134 47 7
267 (44.5%) 336 (55.5%)
(60.7%) (12.6%) (26.7%) (40.0%) (90-100%) (3-5) (49.6%) (5.9%) (3.7%) (0.0%) (94.1%) (2.5-3.0) (3.0-3.5) (18-28) (9-14) (25.9%) (94.1%) (3.0-4.0) (0.0-0.5) (4.4%) (1.5%) (99.3%) (99.3%) (34.8%) (5.2%)
52 (38.5%) 83 (61.5%)
p
(58.5%) (13.4%) (28.1%) (59.6%) (99-100%) (3-5) (52.6%) (40.0%) (20.9%) (5.7%) (60.0%) (2.0-2.5) (2.75-3.5) (18-33) (12-16) (23.8%) (37.9%) (3.0-3.75) (0.0-0.5) (0.4%) (4.9%) (97.0%) (97.7%) (37.4%) (23.0%)
217 (46.2%) 253 (63.8%)
0.139 0.139
Bold values indicate statistically significant differences among groups. IVUS ¼ intra vascular ultra sound; OCT ¼ optical coherence tomography; TIMI ¼ thrombolysis in myocardial infarction. * Expressed as median and interquartile range. † Expressed as mean and standard deviation.
Table 3 Clinical outcomes (patient basis) Variable POCE In-hospital Follow up DOCE In-hospital Follow up Death Cardiac death Any myocardial infarction Target vessel myocardial infarction Target lesion revascularization Target vessel revascularization Stent thrombosis Days of follow-up* Days to POCE*
Overall (n¼563) 38 10 28 31 9 22 10 7 14 13 25 28 9 229 218
(6.7%) (1.8%) (4.9%) (5.5%) (1.6%) (3.9%) (1.8%) (1.2%) (2.5%) (2.3%) (4.4%) (5.0%) (1.6%) (173-360) (150-355)
BVS group (n¼122) 6 0 0 5 0 5 1 0 5 5 5 5 3 193 190
(4.9%) (0.0%) (0.0%) (4.1%) (0.0%) (4.1%) (0.8%) (0.0%) (4.1%) (4.1%) (4.1%) (4.1%) (2.5%) (136-356) (125-352)
EES group (n¼441) 32 10 22 26 9 17 9 7 9 8 20 23 6 239 226
(7.3%) (2.3%) (5.0%) (5.9%) (2.0%) (3.9%) (2.0%) (1.6%) (2.0%) (1.8%) (4.5%) (5.2%) (1.4%) (180-360) (165-355)
P
unadjusted OR
0.365
OR 0.66 (0.3-1.6)
0.444
OR 0.68 (0.3-1.8)
0.383 0.161 0.205 0.148 0.836 0.616 0.399 0.028 0.050
OR 0.40 (0.1-3.2) OR OR OR OR OR
2.05 2.31 0.90 0.78 1.83
(0.7-6.2) (0.7-7.2) (0.3-2.5) (0.3-2.1) (0.5-7.4)
Bold values indicate statistically significant differences among groups. DOCE ¼ device-oriented major adverse cardiac events (death, non fatal vessel related myocardial infarction, target lesion revascularization); POCE ¼ patient-oriented major adverse cardiac events (death, non fatal vessel related myocardial infarction, target lesion revascularization). * Expressed as median and interquartile range.
4
The American Journal of Cardiology (www.ajconline.org)
twenty-two (7.4%) received BVS only, 390 (23.7%) BMS only and 1,096 (66.5%) DES only, whereas 40 patients received a combination of these different devices. Of patients who received DES, 51.4% received at least one EES. All in all, a total of 122 patients or 135 lesions treated only with BVS and 441 patients or 470 lesions treated only with EES were included. Baseline clinical and procedural characteristics are displayed in Tables 1 and 2. Procedural success and inhospital outcome resulted similar in the 2 groups (Table 3). Follow-up was available for all patients. The occurrence of POCE and its single determinants at the longest available follow-up was similar in the 2 groups (4.9% vs 7%, OR 0.68, 0.3 to 1.7, p ¼ 0.407). The KaplaneMeier curves for the occurrence of the primary end point are shown in Figure 1. Device thrombosis occurred in 3 patients (2.5%) of the BVS group, and in 6 (1.4%) of the EES group (OR 1.83, 0.5 to 7.4, p ¼ 0.399). All these thrombotic events were considered as definite and were successfully managed with re-PCI. Propensity-matched analysis basically confirmed results on the basis of multivariate propensity-adjusted analyses (Table 4, Figure 2). On multivariate analysis, baseline Killip class, previous MI, culprit lesion at a bifurcation site, and stent diameter were independent predictors of POCE (Table 5). Figure 1. KaplaneMeier curves for the occurrence of primary study end point POCE (patient-oriented adverse cardiac events).
events adjudication was available for patients included in the Registro Absorb Italiano registry and case report form, but it was not for the cohort of patients receiving EES. Statistical analysis: Data were summarized with counts and percentages for categorical variables, median, and interquartile range for continuous variables with skewed distribution. ManneWhitney U and Fisher’s exact tests were computed when appropriate for bivariate analyses. Cumulative event rates were compared with the log-rank test and summarized as KaplaneMeier estimates. Combined adverse events were evaluated on a hierarchical basis; thus, each patient could provide only one hard event per event type. All variables in Tables 1 and 2 associated with POCE at bivariate analysis (p <0.05) were simultaneously forced into a Cox regression model to identify independent outcome predictors and to calculate their adjusted hazard ratios. To compensate for potential confounding factors inherent to the nonrandomized design of the study, we calculated an individual propensity score, on the basis of the available co-variables and estimated with a nonparsimonious logistic regression model.12 Adjusted odd ratios (ORs) were estimated from models in which the propensity scores were entered as co-variates. In addition, as a sensitivity analysis, we also exploited the propensity score to create matched pairs with a 1:1 ratio based on greedy matching. A 2-tailed p value of 0.05 was considered statistically significant for all analyses (SPSS version 18.0). Results From December 2012 to May 2014, 1,648 patients underwent PPCI at the 11 participating centers. One hundred
Discussion This is the first comparison between BVS and secondgeneration EES in a STEMI population with consecutive patient enrollment and prospective data collection. Our results show a similar rate of POCE between the 2 groups at mid-term follow-up, confirming the favorable profile of ABSORB BVS implanted during PPCI in selected patients with STEMI. The other primary study end point, device thrombosis rate, was similar as well (BVS 2.5% vs EES 1.4%, p ¼ 0.4), and none of these events was fatal. Two recent meta-analyses of patients treated with PPCI during STEMI showed that the implantation of an EES was associated with significantly lower rates of TLR, cardiac death/MI, and ST if compared to other DES or BMS, prizing it as one of the gold standard treatments.5 BVS has been shown to be associated with encouraging clinical results for the treatment of real-world patients.13,14 In particular, patients with STEMI might represent the ideal candidates because of their younger age, with more focal disease and a more limited plaque burden. In the STEMI setting, BVS could overcome the issue of impaired arterial healing, eliminating concerns over incomplete strut endothelialization, neoatherosclerosis, and ST. Single-arm registries have suggested that this new technology can yield good clinical results in patients with STEMI during PPCI.10,15,16 However, very little data are currently available on the clinical comparison between BVS and the “gold standard” EES in the STEMI setting. The results of a multicenter retrospective study comparing the outcomes in matched PPCI cohorts with BVS and EES17 have recently been reported. At 1-year follow-up, the rates of DOCE (4.1% vs 4.1%, p ¼ 0.994) and definite or probable scaffold thrombosis (2.4% vs 1.4%, p ¼ 0.948) were similar. However, a trend toward a more frequent definite or probable early scaffold thrombosis with BVS was observed (2.1% vs 0.3%, p ¼ 0.059).18
Coronary Artery Disease/BVS Versus EES in Primary PCI
5
Table 4 Global and propensity-matched analysis of the 2 study populations P POCE DOCE Death Myocardial infarction Target lesion revascularization Target vessel revascularization Stent thrombosis
0.365 0.444 0.383 0.205 0.836 0.616 0.399
unadjusted OR OR OR OR OR OR OR OR
0.66 0.68 0.40 2.05 0.90 0.78 1.83
(0.3-1.6%) (0.3-1.8%) (0.1-3.2%) (0.7-6.2%) (0.3-2.5%) (0.3-2.1%) (0.5-7.4%)
P
adjusted OR
0.551
OR 0.53 (0.1-4.3%)
0.684 0.352 0.858 0.858 0.514
OR OR OR OR OR
0.38 0.27 0.79 0.79 0.19
(0.1-41.0%) (0.1-4.2%) (0.1-11.2%) (0.1-11.2%) (0.1-27.9%)
DOCE ¼ device-oriented major adverse cardiac events; POCE ¼ patient-oriented major adverse cardiac events.
Table 5 Predictors of POCE (patient basis) Propensity Adjusted OR Hypercholesterolemia Prior MI Killip Class Stent Diameter Bifurcation lesion Direct stenting BVS
2.70 3.41 4.01 0.26 3.32 2.13 1.02
(1.0-7.4) (1.1-11.2) (2.7-6.0) (0.1-0.8) (1.3-8.2) (0.9-5.1) (0.2-5.1)
p 0.054 0.044 0.001 0.023 0.009 0.091 0.982
BVS ¼ bio-vascular scaffold; MI ¼ myocardial infarction; POCE ¼ patient-oriented major adverse cardiac events.
Figure 2. KaplaneMeier curves for the occurrence of the co-primary study end point device thrombosis.
Historically, data from both independent and sponsored randomized clinical studies showed a low incidence of BVS thrombosis. The ABSORB cohort A and B showed any scaffold thrombosis up to 3 years in stable patients.19 The ABSORB II study, a comparison between BVS and EES in a population with stable or unstable angina, showed comparable results in terms of thrombotic events (0.9% vs 0%, p ¼ 0.55).20 The EVERBIO II study, a spontaneous comparison between EES, biolimus-eluting stent, and BVS in an all-comers population (80 patients per group), showed any thrombosis (study in press). In contrast, the Academic Medical Center Registry, a single-center experience in 134 patients with BVS (39% with acute coronary syndrome and 13% STEMI), showed an incidence of 3% of scaffold thrombosis at 6 months.21 The GHOST-EU registry, a large multicenter retrospective registry of 1,189 patients with BVS (16% with STEMI), showed an incidence of ST of 1.5% at 1 month and 2.1% at 6 months. A detailed analysis of these events showed that 61% of these patients did not receive a
scaffold after dilation, whereas 73% had an acute coronary syndrome as a clinical indication for BVS implantation.14 Because of the discrepancies between the aforementioned studies, we analyzed this complication in our population as a co-primary end point of the study. Scaffold thrombosis occurred in 2.5% of patients, a rate not dissimilar to the stent thrombosis rate observed in the EES population at the longest available follow-up. All 3 patients with BVS thrombosis were on DAT. One had ST 5 days after BVS implantation, showed resistance to clopidogrel (on-treatment P2Y12-Reaction-Unit resulted 340) and was switched to ticagrelor after successful re-PPCI. Another patient had a subacute event after 18 days, possibly related to the absence of predilatation and postdilatation during BVS implantation that was also deemed inadequately sized by intracoronary imaging during the redo-PPCI. The third patient had a very late BVS thrombosis (540 days) probably because of the worsening of a stenosis at the distal edge. Preliminary data including ours suggest that this complication needs to be better understood and may be at least partially related to the technique of implantation. This study has several limitations that we want to acknowledge: despite the consecutive and prospective enrollment in both groups, its nature is observational and not randomized; we only have an indirect comparison with EES, partially helped by the propensity-matched analysis. Furthermore, there is an initial bias for device selection in case of tortuous or calcific vessels and for vessels whose size was not suitable for BVS implantation. Finally, the follow-up is relatively limited and an independent events adjudication is not available.
6
The American Journal of Cardiology (www.ajconline.org)
Disclosures There are no potential conflicts of interest or funding sources to disclose.
12. 13.
1. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC) Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van ’t Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569e2619. 2. Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM; TRITON-TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009;373:723e731. 3. Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, Emanuelsson H, Finkelstein A, Husted S, Katus H, Kilhamn J, Olofsson S, Storey RF, Weaver WD, Wallentin L; PLATO Study Group. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: a Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010;122:2131e2141. 4. Kumbhani DJ, Bavry AA, Desai MY, Bangalore S, Bhatt DL. Role of aspiration and mechanical thrombectomy in patients with acute myocardial infarction undergoing primary angioplasty: an updated meta-analysis of randomized trials. J Am Coll Cardiol 2013;62: 1409e1418. 5. Palmerini T, Biondi-Zoccai G, Riva Della D, Mariani A, Sabaté M, Valgimigli M, Frati G, Kedhi E, Smits PC, Kaiser C, Généreux P, Galatius S, Kirtane AJ, Stone GW. Clinical outcomes with drug-eluting and bare-metal stents in patients with ST-segment elevation myocardial infarction: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol 2013;62:496e504. 6. Bangalore S, Amoroso N, Fusaro M, Kumar S, Feit F. Outcomes with various drug-eluting or bare metal stents in patients with ST-segmentelevation myocardial infarction: a mixed treatment comparison analysis of trial level data from 34 068 patient-years of follow-up from randomized trials. Circ Cardiovasc Interv 2013;6:378e390. 7. Diletti R, Yetgin T, Manintveld OC, Ligthart JM, Zivelonghi C, Zijlstra F, Ribichini F. Percutaneous coronary interventions during ST-segment elevation myocardial infarction: current status and future perspectives. EuroIntervention 2014;10(Suppl T):T13eT22. 8. Onuma Y, Serruys PW. Bioresorbable scaffold: the advent of a new era in percutaneous coronary and peripheral revascularization? Circulation 2011;123:779e797. 9. Serruys PW, Garcia-Garcia HM, Onuma Y. From metallic cages to transient bioresorbable scaffolds: change in paradigm of coronary revascularization in the upcoming decade? Eur Heart J 2012;33: 16e25b. 10. Ielasi A, Cortese B, Varricchio A, Tespili M, Sesana M, Pisano F, Loi B, Granata F, Moscarella E, Silva-Orrego P, La Vecchia L, Steffenino G. 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. (in press), Doi:10.4244/EIJY14M10_11. 11. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es G-A, Steg PG, Morel M-A, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research
14.
15.
16.
17.
18.
19.
20.
21.
Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115:2344e2351. Little RJ, Rubin DB. Causal effects in clinical and epidemiological studies via potential outcomes: concepts and analytical approaches. Annu Rev Public Health 2000;21:121e145. Gori T, Schulz E, Hink U, Wenzel P, Post F, Jabs A, Münzel T. Early outcome after implantation of Absorb bioresorbable drug-eluting scaffolds in patients with acute coronary syndromes. EuroIntervention 2014;9:1036e1041. Capodanno D, Gori T, Nef H, Latib A, Mehilli J, Lesiak M, Caramanno G, Naber C, Di Mario C, Colombo A, Capranzano P, Wiebe J, Araszkiewicz A, Geraci S, Pyxaras S, Mattesini A, Naganuma T, Münzel T, Tamburino C. Percutaneous coronary intervention with everolimus-eluting bioresorbable vascular scaffolds in routine clinical practice: early and midterm outcomes from the European multicentre GHOST-EU registry. EuroIntervention 2015;10:1144e1153. Diletti R, Karanasos A, Muramatsu T, Nakatani S, Van Mieghem NM, Onuma Y, Nauta ST, Ishibashi Y, Lenzen MJ, Ligthart J, Schultz C, Regar E, de Jaegere PP, Serruys PW, Zijlstra F, van Geuns RJ. Everolimus-eluting bioresorbable vascular scaffolds for treatment of patients presenting with ST-segment elevation myocardial infarction: BVS STEMI first study. Eur Heart J 2014;35:777e786. Kocka V, Malý M, Tousek P, Budesínský T, Lisa L, Prodanov P, Jarkovský J, Widimsky P. Bioresorbable vascular scaffolds in acute ST-segment elevation myocardial infarction: a prospective multicentre study ’Prague 19’. Eur Heart J 2014;35:787e794. Sabaté M, Cequier A, Iñiguez A, Serra A, Hernandez-Antolin R, Mainar V, Valgimigli M, Tespili M, Heijer den P, Bethencourt A, Vazquez N, Gómez-Hospital JA, Baz JA, Martín-Yuste V, van Geuns RJ, Alfonso F, Bordes P, Tebaldi M, Masotti M, Silvestro A, Backx B, Brugaletta S, van Es GA, Serruys PW. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet 2012;380:1482e1490. Brugaletta S, Gori T, Low AF, Tousek P, Pinar E, Gomez-Lara J, Scalone G, Schulz E, Chan MY, Kocka V, Hurtado J, Gomez-Hospital JA, Münzel T, Lee C-H, Cequier A, Valdés M, Widimsky P, Serruys PW, Sabaté M. Absorb bioresorbable vascular scaffold versus everolimus-eluting metallic stent in ST-segment elevation myocardial infarction: 1-Year results of a propensity score matching comparison: the BVS-EXAMINATION study (Bioresorbable vascular scaffold-a clinical evaluation of everolimus eluting coronary stents in the treatment of patients with ST-segment elevation myocardial infarction). JACC Cardiovasc Interv 2015;8:189e197. Dudek D, Onuma Y, Ormiston JA, Thuesen L, Miquel-Hebert K, Serruys PW. Four-year clinical follow-up of the ABSORB everolimuseluting bioresorbable vascular scaffold in patients with de novo coronary artery disease: the ABSORB trial. EuroIntervention 2012;7: 1060e1061. Serruys PW, Chevalier B, Dudek D, Cequier A, Carrié D, Iñiguez A, Dominici M, van der Schaaf RJ, Haude M, Wasungu L, Veldhof S, Peng L, Staehr P, Grundeken MJ, Ishibashi Y, Garcia-Garcia HM, Onuma Y. 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 2014;385:43e54. Kraak RP, Hassell ME, Grundeken MJ, Koch KT, Henriques JP, Piek JJ, Baan J, Vis MM, Arkenbout EK, Tijssen JG, de Winter RJ, Wykrzykowska JJ. Initial experience and clinical evaluation of the Absorb bioresorbable vascular scaffold (BVS) in real-world practice: the AMC Single Centre Real World PCI Registry. EuroIntervention 2015;10:1160e1168.
a Department of Interventional Cardiology, A.O. Fatebenefratelli, Milano, Italy; bDepartment of Cardiology, A.O. Bolognini, Seriate, Italy; c Department of Cardiology, A.O. Belcolle, Viterbo, Italy; dDepartment of Cardiology, Ospedale Monaldi, Napoli, Italy; eDepartment of Cardiology, A.O. Ospedali Riuniti, Foggia, Italy; fDepartment of Interventional Cardiology, A.O. Brotzu, Cagliari, Italy; gDepartment of Interventional Cardiology, Ospedale Regionale Parini, Aosta, Italy; hCentro di Ricerche Farmacologiche e Biomediche “Mario Negri”, Milano, Italy; iDepartment of Interventional Cardiology, A.O. Desenzano del Garda, Desenzano del Garda, Italy; jDepartment of Interventional Cardiology, Ospedale San Bortolo, Vicenza, Italy; kDepartment of Interventional Cardiology, Policlinico Casilino, Roma, Italy; and lDepartment of Interventional Cardiology, A.O. S.Croce e Carle, Cuneo, Italy. Manuscript received March 18, 2015; revised manuscript received and accepted May 20, 2015. Drs. Cortese and Ielasi equally contributed to the manuscript. See page 6 for disclosure information. *Corresponding author: Tel/fax: (þ39) 0263632210. E-mail address: [email protected] (B. Cortese).
0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.05.049
interventional techniques, administration of more potent antiplatelet drugs, and the evolution from bare metal stents (BMS) to drug-eluting stents (DES) have improved the outcomes of patients with STEMI.2e4 In particular, the cobaltechromium (Co-Cr) everolimus-eluting stent (EESXience; Abbott Vascular, California) has been shown to have a very favorable safety and efficacy profile and may be considered the standard of care for the treatment of patients with STEMI.5,6 Even if the current stent-based reperfusion strategies are associated with a high clinical performance, they have shortcomings related to the durable caging of the coronary wall. Indeed, the implantation of a permanent intracoronary metallic prosthesis may be associated to stent thrombosis (ST), restenosis, and malapposition. To overcome these limitations, new technologies are under investigation in the STEMI setting.7 The ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS, Abbott Vascular) is an intracoronary prosthesis that provides temporary scaffolding and, over a period of 3 years, is fully reabsorbed by biochemical reactions, thus restoring the native pristine vessel state.8,9 The objective of this study was to assess the clinical performance of BVS compared to EES in subjects with STEMI who underwent PPCI. www.ajconline.org
2
The American Journal of Cardiology (www.ajconline.org)
Table 1 Baseline clinical characteristics (patient basis) Variable Age (years)* Women Hypertension Hypercholesterolemia Smoker Family history of CAD Diabetes mellitus Insulin dependent Non-insulin dependent Prior myocardial infarction Prior revascularization Prior percutaneous coronary intervention Prior coronary bypass Peripheral artery disease Multivessel coronary disease Killip class I II III IV Culprit coronary artery Left Anterior Descending Left Circumflex Right
Overall (n¼563) 59 125 327 330 253 173 99 52 47 41 42 39 5 44 278
(52-67) (22.2%) (58.1%) (58.6%) (44.9%) (30.7%) (17.6%) (9.2%) (8.4%) (7.3%) (7.5%) (6.9%) (0.9%) (7.8%) (49.4%)
BVS group (n¼122) 54 31 59 90 60 49 12 5 7 15 13 13 0 1 52
(48-60) (25.4%) (48.4%) (73.8%) (49.2%) (40.2%) (9.8%) (4.1%) (5.7%) (12.3%) (10.7%) (10.7%) (0.0%) (0.8%) (42.6%)
EES group (n¼441) 61 94 268 240 193 124 87 47 40 26 29 26 5 43 226
(53-68) (21.3%) (60.8%) (54.4%) (43.8%) (28.1%) (19.7%) (10.7%) (9.1%) (5.9%) (6.6%) (5.9%) (1.1%) (9.8%) (51.2%)
p
(82.6%) (12.6%) (2.9%) (1.9%)
(91.0%) (8.2%) (0.8%) (0.0%)
(79.9%) (14.0%) (3.6%) (2.5%)
0.001 0.401 0.019 0.001 0.336 0.015 0.016 0.042 0.321 0.027 0.186 0.103 0.525 0.002 0.113 0.026 0.008 0.126 0.206 0.171
334 (59.3%) 75 (13.3%) 154 (27.4%)
74 (60.7%) 16 (13.1%) 32 (26.2%)
260 (59.0%) 59 (13.4%) 122 (27.7%)
0.815 1.000 0.842
Bold values indicate statistically significant differences among groups. BVS ¼ bioresorbable vascular scaffold; Family history of CAD ¼ family history of coronary artery disease; EES ¼ everolimus-eluting stent; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention; CABG ¼ coronary artery by-pass grafting. * Expressed as median and interquartile range.
Methods Aim of this study was to assess the clinical outcomes of consecutive patients with STEMI with symptoms onset <24 hours who underwent PPCI with Absorb-BVS or EES implantation at 11 centers involved in the “Italian ABSORB Registry” (BVS-RAI), a spontaneous, prospective, ongoing multicenter Italian registry without fundings or benefits from the BVS manufacturer (ClinicalTrials.gov identifier is CT02298413). This registry includes all consecutive patients who have successfully undergone unrestricted implantation of 1 BVS. Baseline patient clinical data are entered into a Web-based case report form. The conduct of the registry has been approved by the Ethics Committees of all participating centers. Written informed consent was obtained from all patients to include their data in the database. The registry started in October 2012 and will extend enrollment throughout 2015, with the aims to include 1,000 patients and assess major adverse cardiovascular events (MACE) during a 5-year follow-up. Data on PPCI patients from the BVS-RAI have already been published in part.10 Data from the centers contributing PPCI cases were also collected for all consecutive EES implanted during PPCI in the same time lapse. The full range of sizes and/or lengths for both BVS and EES was available during the study period in all participating centers. Although the decision to implant BVS rather than EES was the operator’s choice, vessel
tortuosity and/or severe calcification proximally to the culprit lesion and infarct artery reference diameter visually exceeding the range of 2.5 to 4 mm were often considered criteria against BVS use. Available lengths for BVS during the study period were 12, 18, and 28 mm. All patients received a loading dose of commonly used antiplatelet drugs periprocedurally. The DAT regimen at discharge consisted in aspirin indefinitely, in association with clopidogrel, ticagrelor, prasugrel for 12 months. Intracoronary imaging, thrombus aspiration, lesion predilatation, and postdilatation (with a maximum diameter of 0.5 mm greater than the BVS diameter) were at the operator’s discretion.10 Primary end points of this study were the cumulative occurrence of POCE (a composite of patient-oriented MACE, including death, MI, target lesion revascularization [TLR]) and device thrombosis at 6-month follow-up. Furthermore, we evaluated procedural success, defined as a final stenosis at the culprit site of <30% with thrombolysis in myocardial infarction 3 flow and without inhospital POCE. Clinical events were defined according to the Academic Research Consortium definitions.11 Furthermore, we differentiated POCE with device-oriented clinical outcome (DOCE). Clinical data were collected by hospital visits at 1 and 6 months. Source verification and queries generation from the coordinating center to the participating sites were undertaken to account partly for the unavoidable bias of site-reported events adjudication. An independent
Coronary Artery Disease/BVS Versus EES in Primary PCI
3
Table 2 Baseline procedural characteristics (lesion basis) Variable Radial approach Treated coronary artery Left Anterior Descending Left Circumflex Right Occluded vessel Stenosis severity* Thrombus score* Thrombectomy use Direct stenting Bifurcational lesions Buddy wire Predilation Predilation balloon diameter (mm)* Stent diameter (mm)* Stent length (mm)* Max pressure during stent implantation† Overlapping stent Post-dilation Postdilation balloon diameter (mm)* Postdilation upsizing (mm) OCT/IVUS guidance Device-related complications Procedural success Final TIMI 3 IIB/IIIA inhibitors administration Bivalirudin Dual antiplatelet therapy ASA þ Clopidogrel ASA þ Ticagrelor/Prasugrel
Overall (n¼605)
BVS group (n¼135)
EES group (n¼ 470)
417 (68.9%)
88 (65.2%)
329 (70.0%)
0.337
275 63 132 280 100 4 247 188 98 27 282 2.5 3.0 23 14 112 178 3.5 0.25 2 23 456 459 176 108
0.715 0.919 0.830 0.001 0.001 0.104 0.616 0.001 0.001 0.009 0.001 0.001 0.009 0.041 0.001 0.699 0.001 0.077 0.221 0.045 0.063 0.246 0.410 0.647 0.001
357 80 168 334 100 4 314 196 103 27 409 2.5 3.0 23 14 147 305 3.5 0.5 8 25 590 593 223 115
(59.0%) (13.2%) (27.8%) (55.2%) (95-100%) (3-5) (51.9%) (32.4%) (17.0%) (4.5%) (67.6%) (2.0-2.5) (2.75-3.5) (18-33) (12-14) (24.3%) (57.7%) (3.0-3.75) (0.0-0.5) (1.3%) (4.1%) (97.5%) (98.0%) (36.9%) (19.0%)
82 17 36 54 99 4 67 8 5 0 127 2.75 3.0 18 10 35 127 3.5 0.5 6 2 134 134 47 7
267 (44.5%) 336 (55.5%)
(60.7%) (12.6%) (26.7%) (40.0%) (90-100%) (3-5) (49.6%) (5.9%) (3.7%) (0.0%) (94.1%) (2.5-3.0) (3.0-3.5) (18-28) (9-14) (25.9%) (94.1%) (3.0-4.0) (0.0-0.5) (4.4%) (1.5%) (99.3%) (99.3%) (34.8%) (5.2%)
52 (38.5%) 83 (61.5%)
p
(58.5%) (13.4%) (28.1%) (59.6%) (99-100%) (3-5) (52.6%) (40.0%) (20.9%) (5.7%) (60.0%) (2.0-2.5) (2.75-3.5) (18-33) (12-16) (23.8%) (37.9%) (3.0-3.75) (0.0-0.5) (0.4%) (4.9%) (97.0%) (97.7%) (37.4%) (23.0%)
217 (46.2%) 253 (63.8%)
0.139 0.139
Bold values indicate statistically significant differences among groups. IVUS ¼ intra vascular ultra sound; OCT ¼ optical coherence tomography; TIMI ¼ thrombolysis in myocardial infarction. * Expressed as median and interquartile range. † Expressed as mean and standard deviation.
Table 3 Clinical outcomes (patient basis) Variable POCE In-hospital Follow up DOCE In-hospital Follow up Death Cardiac death Any myocardial infarction Target vessel myocardial infarction Target lesion revascularization Target vessel revascularization Stent thrombosis Days of follow-up* Days to POCE*
Overall (n¼563) 38 10 28 31 9 22 10 7 14 13 25 28 9 229 218
(6.7%) (1.8%) (4.9%) (5.5%) (1.6%) (3.9%) (1.8%) (1.2%) (2.5%) (2.3%) (4.4%) (5.0%) (1.6%) (173-360) (150-355)
BVS group (n¼122) 6 0 0 5 0 5 1 0 5 5 5 5 3 193 190
(4.9%) (0.0%) (0.0%) (4.1%) (0.0%) (4.1%) (0.8%) (0.0%) (4.1%) (4.1%) (4.1%) (4.1%) (2.5%) (136-356) (125-352)
EES group (n¼441) 32 10 22 26 9 17 9 7 9 8 20 23 6 239 226
(7.3%) (2.3%) (5.0%) (5.9%) (2.0%) (3.9%) (2.0%) (1.6%) (2.0%) (1.8%) (4.5%) (5.2%) (1.4%) (180-360) (165-355)
P
unadjusted OR
0.365
OR 0.66 (0.3-1.6)
0.444
OR 0.68 (0.3-1.8)
0.383 0.161 0.205 0.148 0.836 0.616 0.399 0.028 0.050
OR 0.40 (0.1-3.2) OR OR OR OR OR
2.05 2.31 0.90 0.78 1.83
(0.7-6.2) (0.7-7.2) (0.3-2.5) (0.3-2.1) (0.5-7.4)
Bold values indicate statistically significant differences among groups. DOCE ¼ device-oriented major adverse cardiac events (death, non fatal vessel related myocardial infarction, target lesion revascularization); POCE ¼ patient-oriented major adverse cardiac events (death, non fatal vessel related myocardial infarction, target lesion revascularization). * Expressed as median and interquartile range.
4
The American Journal of Cardiology (www.ajconline.org)
twenty-two (7.4%) received BVS only, 390 (23.7%) BMS only and 1,096 (66.5%) DES only, whereas 40 patients received a combination of these different devices. Of patients who received DES, 51.4% received at least one EES. All in all, a total of 122 patients or 135 lesions treated only with BVS and 441 patients or 470 lesions treated only with EES were included. Baseline clinical and procedural characteristics are displayed in Tables 1 and 2. Procedural success and inhospital outcome resulted similar in the 2 groups (Table 3). Follow-up was available for all patients. The occurrence of POCE and its single determinants at the longest available follow-up was similar in the 2 groups (4.9% vs 7%, OR 0.68, 0.3 to 1.7, p ¼ 0.407). The KaplaneMeier curves for the occurrence of the primary end point are shown in Figure 1. Device thrombosis occurred in 3 patients (2.5%) of the BVS group, and in 6 (1.4%) of the EES group (OR 1.83, 0.5 to 7.4, p ¼ 0.399). All these thrombotic events were considered as definite and were successfully managed with re-PCI. Propensity-matched analysis basically confirmed results on the basis of multivariate propensity-adjusted analyses (Table 4, Figure 2). On multivariate analysis, baseline Killip class, previous MI, culprit lesion at a bifurcation site, and stent diameter were independent predictors of POCE (Table 5). Figure 1. KaplaneMeier curves for the occurrence of primary study end point POCE (patient-oriented adverse cardiac events).
events adjudication was available for patients included in the Registro Absorb Italiano registry and case report form, but it was not for the cohort of patients receiving EES. Statistical analysis: Data were summarized with counts and percentages for categorical variables, median, and interquartile range for continuous variables with skewed distribution. ManneWhitney U and Fisher’s exact tests were computed when appropriate for bivariate analyses. Cumulative event rates were compared with the log-rank test and summarized as KaplaneMeier estimates. Combined adverse events were evaluated on a hierarchical basis; thus, each patient could provide only one hard event per event type. All variables in Tables 1 and 2 associated with POCE at bivariate analysis (p <0.05) were simultaneously forced into a Cox regression model to identify independent outcome predictors and to calculate their adjusted hazard ratios. To compensate for potential confounding factors inherent to the nonrandomized design of the study, we calculated an individual propensity score, on the basis of the available co-variables and estimated with a nonparsimonious logistic regression model.12 Adjusted odd ratios (ORs) were estimated from models in which the propensity scores were entered as co-variates. In addition, as a sensitivity analysis, we also exploited the propensity score to create matched pairs with a 1:1 ratio based on greedy matching. A 2-tailed p value of 0.05 was considered statistically significant for all analyses (SPSS version 18.0). Results From December 2012 to May 2014, 1,648 patients underwent PPCI at the 11 participating centers. One hundred
Discussion This is the first comparison between BVS and secondgeneration EES in a STEMI population with consecutive patient enrollment and prospective data collection. Our results show a similar rate of POCE between the 2 groups at mid-term follow-up, confirming the favorable profile of ABSORB BVS implanted during PPCI in selected patients with STEMI. The other primary study end point, device thrombosis rate, was similar as well (BVS 2.5% vs EES 1.4%, p ¼ 0.4), and none of these events was fatal. Two recent meta-analyses of patients treated with PPCI during STEMI showed that the implantation of an EES was associated with significantly lower rates of TLR, cardiac death/MI, and ST if compared to other DES or BMS, prizing it as one of the gold standard treatments.5 BVS has been shown to be associated with encouraging clinical results for the treatment of real-world patients.13,14 In particular, patients with STEMI might represent the ideal candidates because of their younger age, with more focal disease and a more limited plaque burden. In the STEMI setting, BVS could overcome the issue of impaired arterial healing, eliminating concerns over incomplete strut endothelialization, neoatherosclerosis, and ST. Single-arm registries have suggested that this new technology can yield good clinical results in patients with STEMI during PPCI.10,15,16 However, very little data are currently available on the clinical comparison between BVS and the “gold standard” EES in the STEMI setting. The results of a multicenter retrospective study comparing the outcomes in matched PPCI cohorts with BVS and EES17 have recently been reported. At 1-year follow-up, the rates of DOCE (4.1% vs 4.1%, p ¼ 0.994) and definite or probable scaffold thrombosis (2.4% vs 1.4%, p ¼ 0.948) were similar. However, a trend toward a more frequent definite or probable early scaffold thrombosis with BVS was observed (2.1% vs 0.3%, p ¼ 0.059).18
Coronary Artery Disease/BVS Versus EES in Primary PCI
5
Table 4 Global and propensity-matched analysis of the 2 study populations P POCE DOCE Death Myocardial infarction Target lesion revascularization Target vessel revascularization Stent thrombosis
0.365 0.444 0.383 0.205 0.836 0.616 0.399
unadjusted OR OR OR OR OR OR OR OR
0.66 0.68 0.40 2.05 0.90 0.78 1.83
(0.3-1.6%) (0.3-1.8%) (0.1-3.2%) (0.7-6.2%) (0.3-2.5%) (0.3-2.1%) (0.5-7.4%)
P
adjusted OR
0.551
OR 0.53 (0.1-4.3%)
0.684 0.352 0.858 0.858 0.514
OR OR OR OR OR
0.38 0.27 0.79 0.79 0.19
(0.1-41.0%) (0.1-4.2%) (0.1-11.2%) (0.1-11.2%) (0.1-27.9%)
DOCE ¼ device-oriented major adverse cardiac events; POCE ¼ patient-oriented major adverse cardiac events.
Table 5 Predictors of POCE (patient basis) Propensity Adjusted OR Hypercholesterolemia Prior MI Killip Class Stent Diameter Bifurcation lesion Direct stenting BVS
2.70 3.41 4.01 0.26 3.32 2.13 1.02
(1.0-7.4) (1.1-11.2) (2.7-6.0) (0.1-0.8) (1.3-8.2) (0.9-5.1) (0.2-5.1)
p 0.054 0.044 0.001 0.023 0.009 0.091 0.982
BVS ¼ bio-vascular scaffold; MI ¼ myocardial infarction; POCE ¼ patient-oriented major adverse cardiac events.
Figure 2. KaplaneMeier curves for the occurrence of the co-primary study end point device thrombosis.
Historically, data from both independent and sponsored randomized clinical studies showed a low incidence of BVS thrombosis. The ABSORB cohort A and B showed any scaffold thrombosis up to 3 years in stable patients.19 The ABSORB II study, a comparison between BVS and EES in a population with stable or unstable angina, showed comparable results in terms of thrombotic events (0.9% vs 0%, p ¼ 0.55).20 The EVERBIO II study, a spontaneous comparison between EES, biolimus-eluting stent, and BVS in an all-comers population (80 patients per group), showed any thrombosis (study in press). In contrast, the Academic Medical Center Registry, a single-center experience in 134 patients with BVS (39% with acute coronary syndrome and 13% STEMI), showed an incidence of 3% of scaffold thrombosis at 6 months.21 The GHOST-EU registry, a large multicenter retrospective registry of 1,189 patients with BVS (16% with STEMI), showed an incidence of ST of 1.5% at 1 month and 2.1% at 6 months. A detailed analysis of these events showed that 61% of these patients did not receive a
scaffold after dilation, whereas 73% had an acute coronary syndrome as a clinical indication for BVS implantation.14 Because of the discrepancies between the aforementioned studies, we analyzed this complication in our population as a co-primary end point of the study. Scaffold thrombosis occurred in 2.5% of patients, a rate not dissimilar to the stent thrombosis rate observed in the EES population at the longest available follow-up. All 3 patients with BVS thrombosis were on DAT. One had ST 5 days after BVS implantation, showed resistance to clopidogrel (on-treatment P2Y12-Reaction-Unit resulted 340) and was switched to ticagrelor after successful re-PPCI. Another patient had a subacute event after 18 days, possibly related to the absence of predilatation and postdilatation during BVS implantation that was also deemed inadequately sized by intracoronary imaging during the redo-PPCI. The third patient had a very late BVS thrombosis (540 days) probably because of the worsening of a stenosis at the distal edge. Preliminary data including ours suggest that this complication needs to be better understood and may be at least partially related to the technique of implantation. This study has several limitations that we want to acknowledge: despite the consecutive and prospective enrollment in both groups, its nature is observational and not randomized; we only have an indirect comparison with EES, partially helped by the propensity-matched analysis. Furthermore, there is an initial bias for device selection in case of tortuous or calcific vessels and for vessels whose size was not suitable for BVS implantation. Finally, the follow-up is relatively limited and an independent events adjudication is not available.
6
The American Journal of Cardiology (www.ajconline.org)
Disclosures There are no potential conflicts of interest or funding sources to disclose.
12. 13.
1. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC) Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van ’t Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569e2619. 2. Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM; TRITON-TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009;373:723e731. 3. Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, Emanuelsson H, Finkelstein A, Husted S, Katus H, Kilhamn J, Olofsson S, Storey RF, Weaver WD, Wallentin L; PLATO Study Group. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: a Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010;122:2131e2141. 4. Kumbhani DJ, Bavry AA, Desai MY, Bangalore S, Bhatt DL. Role of aspiration and mechanical thrombectomy in patients with acute myocardial infarction undergoing primary angioplasty: an updated meta-analysis of randomized trials. J Am Coll Cardiol 2013;62: 1409e1418. 5. Palmerini T, Biondi-Zoccai G, Riva Della D, Mariani A, Sabaté M, Valgimigli M, Frati G, Kedhi E, Smits PC, Kaiser C, Généreux P, Galatius S, Kirtane AJ, Stone GW. Clinical outcomes with drug-eluting and bare-metal stents in patients with ST-segment elevation myocardial infarction: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol 2013;62:496e504. 6. Bangalore S, Amoroso N, Fusaro M, Kumar S, Feit F. Outcomes with various drug-eluting or bare metal stents in patients with ST-segmentelevation myocardial infarction: a mixed treatment comparison analysis of trial level data from 34 068 patient-years of follow-up from randomized trials. Circ Cardiovasc Interv 2013;6:378e390. 7. Diletti R, Yetgin T, Manintveld OC, Ligthart JM, Zivelonghi C, Zijlstra F, Ribichini F. Percutaneous coronary interventions during ST-segment elevation myocardial infarction: current status and future perspectives. EuroIntervention 2014;10(Suppl T):T13eT22. 8. Onuma Y, Serruys PW. Bioresorbable scaffold: the advent of a new era in percutaneous coronary and peripheral revascularization? Circulation 2011;123:779e797. 9. Serruys PW, Garcia-Garcia HM, Onuma Y. From metallic cages to transient bioresorbable scaffolds: change in paradigm of coronary revascularization in the upcoming decade? Eur Heart J 2012;33: 16e25b. 10. Ielasi A, Cortese B, Varricchio A, Tespili M, Sesana M, Pisano F, Loi B, Granata F, Moscarella E, Silva-Orrego P, La Vecchia L, Steffenino G. 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. (in press), Doi:10.4244/EIJY14M10_11. 11. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es G-A, Steg PG, Morel M-A, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research
14.
15.
16.
17.
18.
19.
20.
21.
Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115:2344e2351. Little RJ, Rubin DB. Causal effects in clinical and epidemiological studies via potential outcomes: concepts and analytical approaches. Annu Rev Public Health 2000;21:121e145. Gori T, Schulz E, Hink U, Wenzel P, Post F, Jabs A, Münzel T. Early outcome after implantation of Absorb bioresorbable drug-eluting scaffolds in patients with acute coronary syndromes. EuroIntervention 2014;9:1036e1041. Capodanno D, Gori T, Nef H, Latib A, Mehilli J, Lesiak M, Caramanno G, Naber C, Di Mario C, Colombo A, Capranzano P, Wiebe J, Araszkiewicz A, Geraci S, Pyxaras S, Mattesini A, Naganuma T, Münzel T, Tamburino C. Percutaneous coronary intervention with everolimus-eluting bioresorbable vascular scaffolds in routine clinical practice: early and midterm outcomes from the European multicentre GHOST-EU registry. EuroIntervention 2015;10:1144e1153. Diletti R, Karanasos A, Muramatsu T, Nakatani S, Van Mieghem NM, Onuma Y, Nauta ST, Ishibashi Y, Lenzen MJ, Ligthart J, Schultz C, Regar E, de Jaegere PP, Serruys PW, Zijlstra F, van Geuns RJ. Everolimus-eluting bioresorbable vascular scaffolds for treatment of patients presenting with ST-segment elevation myocardial infarction: BVS STEMI first study. Eur Heart J 2014;35:777e786. Kocka V, Malý M, Tousek P, Budesínský T, Lisa L, Prodanov P, Jarkovský J, Widimsky P. Bioresorbable vascular scaffolds in acute ST-segment elevation myocardial infarction: a prospective multicentre study ’Prague 19’. Eur Heart J 2014;35:787e794. Sabaté M, Cequier A, Iñiguez A, Serra A, Hernandez-Antolin R, Mainar V, Valgimigli M, Tespili M, Heijer den P, Bethencourt A, Vazquez N, Gómez-Hospital JA, Baz JA, Martín-Yuste V, van Geuns RJ, Alfonso F, Bordes P, Tebaldi M, Masotti M, Silvestro A, Backx B, Brugaletta S, van Es GA, Serruys PW. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet 2012;380:1482e1490. Brugaletta S, Gori T, Low AF, Tousek P, Pinar E, Gomez-Lara J, Scalone G, Schulz E, Chan MY, Kocka V, Hurtado J, Gomez-Hospital JA, Münzel T, Lee C-H, Cequier A, Valdés M, Widimsky P, Serruys PW, Sabaté M. Absorb bioresorbable vascular scaffold versus everolimus-eluting metallic stent in ST-segment elevation myocardial infarction: 1-Year results of a propensity score matching comparison: the BVS-EXAMINATION study (Bioresorbable vascular scaffold-a clinical evaluation of everolimus eluting coronary stents in the treatment of patients with ST-segment elevation myocardial infarction). JACC Cardiovasc Interv 2015;8:189e197. Dudek D, Onuma Y, Ormiston JA, Thuesen L, Miquel-Hebert K, Serruys PW. Four-year clinical follow-up of the ABSORB everolimuseluting bioresorbable vascular scaffold in patients with de novo coronary artery disease: the ABSORB trial. EuroIntervention 2012;7: 1060e1061. Serruys PW, Chevalier B, Dudek D, Cequier A, Carrié D, Iñiguez A, Dominici M, van der Schaaf RJ, Haude M, Wasungu L, Veldhof S, Peng L, Staehr P, Grundeken MJ, Ishibashi Y, Garcia-Garcia HM, Onuma Y. 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 2014;385:43e54. Kraak RP, Hassell ME, Grundeken MJ, Koch KT, Henriques JP, Piek JJ, Baan J, Vis MM, Arkenbout EK, Tijssen JG, de Winter RJ, Wykrzykowska JJ. Initial experience and clinical evaluation of the Absorb bioresorbable vascular scaffold (BVS) in real-world practice: the AMC Single Centre Real World PCI Registry. EuroIntervention 2015;10:1160e1168.