Author + information
- Received November 2, 2010
- Revision received February 7, 2011
- Accepted February 22, 2011
- Published online July 12, 2011.
- Roberto Diletti, MD⁎,
- Yoshinobu Onuma, MD⁎,
- Vasim Farooq, MBChB⁎,
- Josep Gomez-Lara, MD⁎,
- Salvatore Brugaletta, MD⁎,
- Robert Jan van Geuns, MD, PhD⁎,
- Evelyn Regar, MD, PhD⁎,
- Bernard de Bruyne, MD†,
- Dariusz Dudek, MD‡,
- Leif Thuesen, MD§,
- Bernard Chevalier, MD∥,
- Dougal McClean, MD¶,
- Stephan Windecker, MD, PhD#,
- Robert Whitbourn, MD⁎⁎,
- Pieter Smits, MD, PhD††,
- Jacques Koolen, MD‡‡,
- Ian Meredith, MBBS, PhD§§,
- Dong Li, MSc∥∥,
- Susan Veldhof, RN∥∥,
- Richard Rapoza, PhD¶¶,
- Hector M. Garcia-Garcia, MD, PhD##,
- John A. Ormiston, MBChB, PhD⁎⁎⁎ and
- Patrick W. Serruys, MD, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence
: Dr. Patrick W. Serruys, Department of Interventional Cardiology, Erasmus Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands
Objectives We investigated the 6-month clinical outcomes after implantation of second-generation 3.0-mm bioresorbable everolimus-eluting vascular scaffolds (BVS) in small coronary vessels (<2.5 mm).
Background BVS are a novel approach to treating coronary lesions and are untested in small vessels.
Methods The ABSORB Cohort B Trial is a multicenter, single-arm, prospective, open-label trial assessing the performance of the second-generation BVS, in which 101 patients were enrolled. The pre-procedural reference vessel diameter (RVD) was assessed by quantitative coronary angiography during post hoc analysis. The vessel size was overestimated, by visual assessment, in 41 patients before implantation of 3.0-mm BVS in vessels with a pre-procedural RVD <2.5 mm. The study population was divided into 2 groups, group I (n = 41) with RVD <2.5 mm and group II (n = 60) with RVD ≥2.5 mm. The composite endpoint of ischemia-driven major adverse cardiac events, defined as ischemia-driven target lesion revascularization, myocardial infarction, or cardiac death, was assessed. Of the 45 patients scheduled for 6-month coronary angiography, 42 patients had the procedure performed, with intravascular ultrasound undertaken in 40 of these patients.
Results At 6 months, no significant differences in ischemia-driven major adverse cardiac events (3 of 41 [7.3%] cases vs. 2 of 60 [3.3%] cases; p = 0.3933) were observed in the small- and large-vessel groups, respectively. No cardiac deaths or episodes of in-scaffold thromboses were seen. Angiographic and intravascular ultrasound follow-up demonstrated no differences in late lumen loss (0.16 ± 0.18 mm vs. 0.21 ± 0.17 mm; p = 0.3525) or percentage lumen area stenosis (17.6 ± 6.0% vs. 19.8 ± 8.5%; p = 0.3643).
Conclusions The second-generation 3.0-mm BVS appears to be safe in small vessels, with similar clinical and angiographic outcomes compared with those of large vessels.
Fully bioresorbable drug-eluting vascular scaffolds (BVS, Abbott Vascular, Santa Clara, California) are a novel approach to treating coronary lesions in that they provide transient vessel support and drug delivery to the vessel wall. The first-generation BVS demonstrated slightly higher acute and late recoil when compared with conventional metallic stents. (1,2) To further enhance support of the vessel wall, the strut design and manufacturing processes of the polymer were modified, leading to the BVS revision 1.1; this device was subsequently investigated in the ABSORB Cohort B trial. Because of the single size availability of the BVS (3.0 mm in diameter), the target lesions were required to be located in vessels with a visually estimated vessel diameter of 3.0 mm. However, during the clinical use of BVS, more than one-third of the scaffolds were found to have been deployed in vessels with a pre-procedural reference vessel diameter (RVD) <2.5 mm. This protocol deviation has provided the opportunity to assess the performance of the 3.0-mm BVS device in these vessels.
The purpose of this substudy was therefore to investigate the clinical and angiographic outcomes after implantation of the new generation of BVS in small coronary vessels (RVD <2.5 mm).
Study design and population
The study design and device have previously been described (3). In brief, 101 patients were enrolled in the ABSORB Cohort B study and implanted with 3-mm BVS. Assessment of vessel size before BVS implantation was made by visual estimation of the operator. In the present post hoc analysis, the study population was divided into 2 groups based on the RVD before intervention. Group I included 41 patients (41 lesions) with an RVD <2.5 mm, and group II included 60 patients (61 lesions) with an RVD ≥2.5 mm. Of the 45 patients initially scheduled for 6- and 24-month coronary angiography, 42 patients underwent the procedure at the 6-month follow-up, with intravascular ultrasound (IVUS) analyses performed in 40 cases.
Quantitative coronary angiography and IVUS analysis
In all patients, analyses were performed with quantitative coronary angiography (QCA) using a coronary angiography analysis system (Pie Medical Imaging, Maastricht, the Netherlands). The RVD was obtained by the interpolated method (4). Post-procedural and follow-up scaffold segments were analyzed with phased-array IVUS catheters (EagleEye, Volcano Corporation, Rancho Cordova, California), with an automated pullback of 0.5 mm/s. Images were analyzed offline with semiautomatic contour detection provided by dedicated software, as previously reported (3).
Categorical variables are presented as counts and percentages. Continuous variables are presented as mean ± SD. The p values were calculated with the Fisher exact test for binary variables and Wilcoxon rank-sum test for continuous variables. All p values were calculated for descriptive purposes and did not form part of formal hypothesis tests. Statistical analyses were performed using SAS (version 9.1.3, SAS Institute, Inc., Cary, North Carolina).
Baseline characteristics and procedural outcomes
In the ABSORB Cohort B Trial, 101 patients were enrolled and 102 lesions treated with implantation of BVS. Forty-one lesions had an RVD <2.5 mm, and 61 lesions had an RVD ≥2.5 mm (Fig. 1). In the small-vessel group, 34 lesions (83%) were located in the mid or distal part of main coronary arteries or in secondary branches. No significant differences in baseline demographic characteristics were seen in both groups (Table 1). Comparable pre-procedural percentage diameter stenoses (57.0 ± 9.3% vs. 60.3 ± 10.3%; p = 0.1000) and post-procedural acute gains (1.21 ± 0.30 mm vs. 1.25 ± 0.33 mm; p = 0.4946) were observed (Table 2).
No statistically significant differences were observed in the incidences of both in-hospital (small-vessel group 2 of 41 cases [4.9%]; large-vessel group 0 of 60 cases [0%]; p = 0.1624) and 6-month (small-vessel group 3 of 41 cases [7.3%]; large-vessel group 2 of 60 cases [3.3%]; p = 0.3933) major adverse cardiac events (MACE) in both groups (Table 3). At 6 months, the incidences of ischemia-driven target lesion revascularizations (ID-TLR) (1 of 41 patients [2.4%] vs. 1 of 60 patients [1.7%]; p = 1.0000), target vessel revascularizations (2.4% vs. 1.7%; p = 1.0000), and myocardial infarctions (2 of 41 patients [4.9%] vs. 1 of 60 patients [1.7%]; p = 0.5645) were similar in both groups, with no cardiac deaths observed. At 6 months, no episodes of scaffold thromboses, as defined by the Academic Research Consortium (5), were reported. One episode of a non-ID-TLR event was seen in the large-vessel group.
6-month angiographic and IVUS results
QCA analyses at 6 months were available for 42 patients (small-vessel group n = 19; large-vessel group n = 23). No statistical differences in scaffold percentage diameter stenoses (18.1 ± 7.2% vs. 20.2 ± 8.0%; p = 0.3736) and in scaffold late loss (0.16 ± 0.18 mm vs. 0.21 ± 0.17 mm; p = 0.3525) were observed between both groups. No cases of binary restenosis within the scaffold were evident in either group (Table 4).
Grey-scale IVUS analyses demonstrated no statistically significant differences in lumen area stenosis (17.6 ± 6.0% vs. 19.8 ± 8.5%; p = 0.3643) or neointimal hyperplasia area (0.06 ± 0.12 mm2 vs. 0.09 ± 0.12 mm2; p = 0.4084) between the 2 groups (Table 5,Fig. 2).
However, the comparison of IVUS results is limited by the small number of available data; a post hoc power analysis showed that with this sample size, a difference in neointimal hyperplasia area of 0.11 mm2 could be detected with 80% power.
Case descriptions of MACE and non–ID-TLR events
In the small-vessel group, 3 MACE were reported. In the first patient (RVD 2.05 mm), the 6-month scheduled angiography disclosed a proximal-edge stenosis in the mid right coronary artery that was subsequently treated. Of note is that during the index procedure, the operator deeply inserted the Amplatz guide catheter into the mid right coronary artery; the possibility of endothelial denudation therefore cannot be excluded as a potential cause of the restenosis. In the second patient (RVD 2.15 mm), pre-dilation of the lesion provoked a dissection that became occlusive after incomplete lesion coverage with the BVS. Subsequent bailout stenting was performed. The peak value of troponin was 0.8 ng/ml (upper limit of normal [ULN] <0.03 ng/ml), creatine kinase (CK) 521 U/l (ULN <180 U/l), and CK-MB 48 U/l (ULN <5 U/l). This case was adjudicated as peri-procedural non–Q-wave myocardial infarction. In the third patient (RVD 2.18 mm), a nonocclusive dissection occurred after lesion pre-dilation; however, the dissection was fully covered with BVS. The electrocardiogram remained unremarkable. Subsequent troponin, CK, and CK-MB levels, however, peaked at 0.81 ng/ml (ULN <0.03 ng/ml), 667 U/l (ULN <150 U/l), and 97.2 ng/ml (ULN <4 ng/ml), respectively.
In the large-vessel group, 2 MACE were reported. In the first patient (RVD 2.51 mm), BVS was implanted in the left anterior descending artery with a myocardial bridge. Three months later, the patient presented with recurrent angina. Repeat coronary angiography demonstrated a diameter stenosis of 40% and 85% in diastole and systole, respectively, resulting in the implantation of a metallic everolimus-eluting stent. In the second patient (RVD 2.74 mm), an iatrogenic non–Q-wave myocardial infarction (CK 600 U/l, CK-MB 72 U/l, ≥2× ULN) was caused by thrombus formation following an IVUS examination, during a failed attempt at imaging the vessel with optical coherence tomography (OCT).
In a separate patient, 3.0-mm BVS was post-dilated with a larger 3.5-mm semicompliant balloon to 16 atmospheres (expected diameter 3.96 mm). Post-procedural OCT revealed several scaffold pattern irregularities but with a 20% diameter stenosis; consequently, there was no further intervention. Thirty-three days later, the patient was readmitted because of recurrent nocturnal chest pain. Coronary angiography demonstrated a nonsignificant diameter stenosis of 23%. OCT however, revealed multiple scaffold pattern irregularities in the proximal half of the BVS with several struts appearing in the middle of the lumen. A 3.5-mm drug-eluting stent (DES) was deployed in the proximal BVS with a satisfactory result. This event was adjudicated as being a non–ID-TLR by the Clinical Events Committee.
The present substudy of ABSORB Cohort B is the first to report the use of a completely bioresorbable everolimus-eluting scaffold in the setting of small-vessel disease. The major findings of this substudy were: 1) patients who underwent BVS implantation in small vessels had 6-month clinical outcomes similar to those of patients who underwent the procedure in large vessels; and 2) implantation of 3-mm BVS in small vessels was associated with equivalent late luminal loss, percentage diameter stenosis, and binary restenosis rates, compared with those of large vessels.
Small-vessel coronary artery disease is a recognized challenging subset within the field of coronary artery intervention in that balloon angioplasty and bare metal stents have previously demonstrated unacceptable rates of restenosis and MACE (6,7). The use of DES in this setting has, however, led to more acceptable long-term results, although important differences in types of DES appear to exist (8,9).
In the present study, despite the implantation of larger (3.0-mm) BVS in small vessels (<2.5 mm), no significant differences in clinical outcomes were observed in both groups at 6 months. In the small-vessel group, all 3 cases may possibly have been explained by procedural-related complications and not due to device failure itself. However, because of the small sample size and low incidence rate in this study, caution should be taken in making firm conclusions with regards to safety and efficacy.
A high degree of vessel stretch and injury, smaller post-procedural lumen area, and a high metal density have all previously been proposed as contributing factors to explain the poorer outcomes associated with small vessels (10). Current consensus, however, is that the so-called “bigger is better” paradigm (11) is likely to be the most plausible mechanism to explain the poorer outcomes associated with small-vessel disease. Effectively, a smaller vessel size would be less able to accommodate the same absolute volume of neointimal hyperplasia as a larger vessel, with the resultant increase in the rate of binary restenosis. The other potential concern is the thickness of the BVS struts (150 μm) because previous studies have suggested a link between thicker struts and an increased risk of restenosis (12); these concerns, however, did not appear to be evident in this present study.
Vessels with RVD <2.5 mm were treated with 3.0-mm BVS pre-mounted on a 3.0-mm diameter balloon. This factor may have played a role in the similar angiographic and clinical outcomes observed between the 2 groups. Further study of this device is currently being undertaken in the multicenter ABSORB Extend Single-Arm Study, in which the introduction of a 2.5-mm BVS device is planned. This 2.5-mm BVS device is actually the same scaffold as the 3.0 mm but crimped onto a smaller 2.5-mm balloon and is intended for the treatment of vessels ≥2.0 and ≤3.0 mm. This smaller device may aid in further understanding whether the impact of a larger (3.0-mm) deployment balloon size played any significant role in the excellent outcomes seen with the device in small vessels.
It would therefore appear that the concerns of BVS implantation in small vessels may not be justified, whereas the risk of excessive post-dilation of the BVS appears to be of more concern. Appropriate sizing of the vessel with QCA analysis and respect for the maximal diameter limits of the BVS are therefore currently required.
The present study was a post hoc analysis, and the number of patients was limited. Therefore, p values presented are exploratory and should be interpreted with caution. Second, coronary angiography is limited to the detection of the lumen contour, without the actual vessel size being taken into account. IVUS allows assessment of the vessel size; however, IVUS was not performed before BVS implantation in the present study.
The 3.0-mm BVS appears to be safe and effective in small vessels, with similar clinical and angiographic outcomes observed when compared with those of large vessels.
Dr. Dudek has received research grants or served as consultant/advisory board member for Abbott, Adamed, Biotronik, Balton, Bayer, BBraun, BioMatrix, Boston Scientific, Boehringer Ingelheim, Bristol-Myers Squibb, Cordis, Cook, Eli Lilly, EuroCor, GlaxoSmithKline, Invatec, Medtronic, The Medicines Company, MSD, Nycomed, Orbus-Neich, Pfizer, Possis, Promed, Sanofi-Aventis, Siemens, Solvay, Terumo, and Tyco. Dr. Chevalier is a consultant to Abbott Vascular. Dr. Windecker has received research grants from Abbott, Cordis, Biotronik, and Medtronic. Dr. Smits has received fees from Abbott Vascular. Mr. Li, Ms. Veldhof, and Dr. Rapoza are employed by Abbott Vascular. Dr. Ormiston is on the advisory board of and has received honoraria from Abbott Vascular and Boston Scientific. Dr. Serruys is a member of the Abbott Vascular BVS Scientific Advisory Group. All other authors have reported that they have no relationships to disclose.
- Abbreviations and Acronyms
- bioresorbable drug-eluting vascular scaffolds
- creatine kinase
- drug-eluting stent(s)
- ischemia-driven target lesion revascularization
- intravascular ultrasound
- major adverse cardiac event(s)
- optical coherence tomography
- quantitative coronary angiography
- reference vessel diameter
- Received November 2, 2010.
- Revision received February 7, 2011.
- Accepted February 22, 2011.
- American College of Cardiology Foundation
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