The REVA scaffold (REVA Medical, Inc., San Diego, CA, USA) is a poly (iodinated desamino tyrosyl-tyrosine ethyl ester) carbonate device composed of iodinated-desaminotyrosinetyrosine. Following absorption, water, carbon dioxide, ethanol and iodinated-desaminotyrosinetyrosine are the end products from the Krebs cycle and excreted from the body. The REVA scaffold has no anti-proliferative drug coating and the bioresorption time is nearly 36 months. The slide and locking design prevented deformation and weakening of the polymer during scaffold deployment (Fig.
1). The radial force of the REVA scaffold has been reported to be greater than the MULTILINK BMS [
40]. In the RESORB study, in which 27 patients with de novo lesions were enrolled, acute gain in lumen diameter and vessel shrinkage were satisfactory following device implantation. The mean diameter stenosis pre- and post implantation were 70 % and 5.9 % respectively. The pre-implantation and post-implantation lumen diameters were 0.88 ± 0.39 mm and 2.76 ± 0.36 mm, respectively. Despite these results, at 6-months follow-up LLL was 1.81 mm and TLR was 66.7 %, predominantly secondary to vessel recoil since the neo-intimal hyperplasia response was shown to be similar compared to BMS [
41]. Following these findings, the scaffold has been redesigned and the second-generation ReZolve stent has stiff radiopaque polymer, a spiral ‘slide and lock’ mechanism and is coated with the antiproliferative drug sirolimus. In the RESTORE study, with 50 patients at 12 months follow-up, acute recoil was 3.8 ± 6.7 %, and LLL was 0.29 ± 0.33 mm at 12 months. At 6 months there were 2 MACE events in 12 patients [
42]. Further improvements in the design of the scaffold have concluded in REVA’s current product. ReZolve2 is being tested in the Safety and Performance Study of the ReZolve2 Sirolimus-Eluting Bioresorbable Coronary Scaffold study (RESTORE-II) (
n = 125) [
43]. The company has presented a new clinical trial program named FANTOM investigating Fantom bioresorbable sccaffold with thinner strut thickness [
44].
Myolimus-eluting Poly-L-Lactic acid scaffold: DESolve
The DESolve Myolimus-Eluting Bioresorbable Coronary Scaffold System has a poly L-lactic acid (PLLA) backbone and is coated with myolimus (3 mg/mm) - a sirolimus analogue. In porcine studies, the radial strength was sufficiently provided over a 3 month period, and the resorption phase was completed at up to 2-years [
47]. In the multicentre DESolve-I FIM trial, which recruited 16 patients implanted with polylactide-based bioresorbable scaffold coated with bioabsorbable polymer eluting myolimus, the incidence of acute recoil was 6.4 % and the LLL was 0.19 mm at 6 months. Post-procedural IVUS analyses demonstrated a mean scaffold area 5.35 mm
2 and a mean lumen area of 5.35 mm
2. Six-month IVUS analyses did not significantly differ from the baseline IVUS with a mean scaffold area 5.61 mm
2 and mean lumen area 5.10 mm
2. Six-month optical coherence tomography (OCT) examination at follow-up demonstrated that 98.7 % of the struts to be covered by neointima. One-year clinical follow up demonstrated 3 MACE, 1 target vessel MI and 1 TLR; no patient was reported to have had a scaffold thrombosis [
47]. In the multi-center, prospective DESolve Nx trial, 120 patients were treated with the DESolve Nx device - a PLLA-based polymer scaffold that is coated with novolimus (5 mg/mm), which is an active metabolite of sirolimus [
48,
49]. Recruitment of patients in the trial has been completed and clinical follow-up is still on-going. DESolve Nx trial was successful in demonstrating the safety and efficacy of the DESolve scaffold, with a low 6-month LLL by QCA (0.20 ± 0.32 mm), low 6-month IVUS % volume obstruction (5 %), low 6-month neointimal hyperplasia (NIH) thickness by OCT (0.10 mm), sustained neointimal suppression through 18 months follow-up, low 24-month MACE rate (7.4 %), no reported late acquired incomplete strut apposition (ISA) by IVUS / OCT at 6 months and high percentage of strut coverage by OCT at 6 months (98.8 %) [
48,
49]. The preclinical study for the next generation scaffold named DEsolve 100 with reduced strut thickness (100 μm) is ongoing.
Everolimus-eluting Poly-L-lactic acid scaffold (Absorb BVS)
The Abbott Vascular everolimus eluting bioresorbable vascular scaffold (ABSORB BVS) (Abbott Vascular, Santa Clara, CA, USA) has a backbone of PLLA, coated with layer of a 1:1 mixture of an amorphous matrix of poly-D, L-lactide (PDLLA) and an antiproliferative drug everolimus (8.2 μg/mm). The PDLLA controls the release of everolimus, 80 % of which is eluted at the end of the first month following implantation. The first version of Absorb BVS (Absorb BVS 1.0) had a strut thickness of 150 μm, a crossing profile of 1.4 mm, and constituted of circumferential out-of-phase zigzag hoops, with the struts linked directly together by thin and straight connections. In the first human study, ABSORB (
n = 30), multimodality intravascular imaging including IVUS, IVUS-virtual histology (IVUS-VH), palpography and OCT were performed at 6-month and 2-years follow up. At 6-month clinical follow-up, there was only one ischemic driven major adverse event (non Q-wave myocardial infarction); in the following 42-months there were no reported MACE events [
22,
50]. At the 4-year clinical follow-up there was no ST [
51]. At 5-years the overall MACE event rate was 3.4 %. At 6-months follow-up LLL was 0.44 mm. The reduction in lumen area was 16.6 %, and the late recoil was 11.7 % [
52]. The loss of radial strength with bioresorption, that was considered a consequence of scaffold shrinkage (6.94 ± 1.70 mm
2 to 6.29 ± 1.47 mm
2 at the 6 months follow-up), prompted the redesign of the scaffold. The re-designed Absorb BVS 1.1 had a strut design with in-phase hoops and straight links to provide additional radial support, and an updated polymer to provide additional mechanical strength for the scaffold [
53]. The second generation ABSORB BVS was evaluated in the ABSORB Cohort B study. The studied population was divided into 2 groups; the first group (B1) had QCA, IVUS, IVUS palpography, IVUS-VH, IVUS echogenicity, and OCT at 6 months and 2 years. The second group (B2) had the same follow-up imaging processes at 1 and at 3 years. At 2 year clinical follow up overall MACE was 9.0 % [
54]. In Cohort B1, IVUS analyses demonstrated the minimal lumen area to decrease during the 6-months follow-up (baseline: 6.60 ± 1.22 mm
2 , 6-month:,
P < 0.005), and to remain stable between 6-months and 2-years follow-up (6-month: 6.37 ± 1.12 mm
2, 24-month: 5.99 ± 1.61 mm
2,
P = 0.26). On OCT evaluation, the scaffold area progressively increased (baseline: 7.47 ± 1.18 mm
2, 6-months: 7.70 ± 1.34 mm
2, 2-years 8.34 ± 1.83 mm
2).
In Cohort B2, the mean scaffold area did not significantly change between post-implantation and 12-months in OCT and IVUS examinations. The vessel vasomotion was tested with the application of acetylcholine or methylergonovine and the lumen measurements during these tests elicited restoration of the vasomotion at 12 months after scaffold implantation [
55]. At two years, intracoronary administration of nitrate was performed and a significant (
p = 0.035) but modest (0.034 ± 0.09 mm) vasodilatation was demonstrated. At three years, the vasodilatation was improved (0.054 ± 0.12 mm,
p = 0.005) [
56]. Subsequently, preliminary results from the international, multi-center ABSORB EXTEND single arm study demonstrated an incidence of MACE of 7.3 %, ischemia driven TLR of 4.0 %, and stent thrombosis of 0.8 %, in 250 patients with 24 months of clinical follow-up [
57].
ABSORB II constitutes the first randomized controlled trial comparing the efficacy and safety of a 2nd generation bioresorbable scaffold (Absorb, Abbott Vascular, Santa Clara, CA, USA) with a contemporary DES (Xience, Abbott Vascular, Santa Clara, CA, USA). The ABSORB II trial had a 2:1 single-masked design, recruiting 501 patients with stable and unstable angina symptoms to treatment with an everolimus eluting bioresorbable scaffold or a contemporary everolimus eluting metallic DES. The procedural details of the study were shown in Table
2. The co-primary endpoints of nitrate-induced vasomotion and changes in minimum lumen diameter (in-stent late loss) are to be reported at 3 years. Secondary outcomes recently reported at 1 year demonstrated no difference in major adverse cardiovascular events (defined as death, myocardial infarction or target lesion revascularization) between patients treated with a bioresorbable or a contemporary metallic DES (5 % vs. 3 %,
P = 0.35). In addition, cumulative rates of first new or worsening angina were reported to be lower with the bioresorbable scaffold group compared to contemporary metallic DES (22 % vs. 30 %,
p = 0.04), whereas the performance during maximum exercise and angina status by Seattle Angina Questionnaire were reported to be similar [
57].
Table 2
Procedural details of ABSORB II trial
Number of lesions | 364 | 182 | | |
Balloon dilatation prior to device implantation | 364 (100 %) | 180 (99 %) | 1.10 % (−0.21, 3.92) | 0.11 |
Planned overlap with the same type of device | 56 (15 %) | 20 (11 %) | 4.40 % (−1.93, 9.94) | 0.16 |
Additional implantation with the same device | 14 (4 %) | 11 (6.0) | −2.20 % (−6.91, 1.44) | 0.25 |
More than one study device implanted | 70 (19 %) | 27 (15 %) | 4.40 % (−2.57, 10.62) | 0.21 |
Nominal size of study device (mm) | 3.01 (0.31) | 3.05 (0.28) | −0.04 (−0.10, 0.01) | 0.10 |
Balloon dilatation after device implantation | 221 (61 %) | 107 (59 %) | 1.92 % (−6.66, 10.67) | 0.67 |
Nominal diameter of balloon used (mm) | 3.08 (0.34) | 3.16 (0.36) | −0.08 (−0.14, 0.01) | 0.02 |
Maximum balloon pressure used (atm) | 14.23 (3.43) | 15.03 (3.33) | −0.80 (−1.4, −0.2) | 0.01 |
Diameter of balloon used (mm) | 3.29 (0.35) | 3.35 (0.37) | −0.06 (−0.14, 0.02 ) | 0.15 |
Angiographic acute recoil of device following implantation per device (mm) | 0.19 (0.19) | 0.19 (0.18) | −0.00 (−0.04, 0.03) | 0.85 |
Device success | | | | |
Clinical device success | 361 (99 %) | 182 (100 %) | −0.82 % (−2.39, 1.31) | 0.55 |
Clinical procedural success | 322 (96 %) | 164 (99 %) | −2.68 % (−5.46, 0.80) | 0.16 |
In ABSORB II, pre-procedure mean lumen area in the BVS and metallic stent groups were reported to be similar 4.84 ± 1.39 mm
2 and 5.02 ± 1.47 mm
2, respectively (
p = 0.16). The post-procedure mean lumen area were 6.06 ± 1.44 mm
2 and 6.85 ± 1.60 mm
2 respectively (
p < 0.001). Post-procedure acute gain in minimum lumen diameter was significantly larger in metallic stent group than in BRS group (1.46 ± 0.38 mm vs 1.15 ± 0.38 mm, respectively;
p < 0.001). Post-procedure in-stent/in-scaffold diameter stenosis was larger in BRS group than in metallic stent group (16 ± 7 % vs 10 ± 5 %, respectively;
p < 0.001). In post-procedure IVUS analyses, post-procedure mean lumen area was significantly less in BVS group than in metallic stent group (6.06 ± 1.44 mm
2 vs 6.85 ± 1.60 mm
2, respectively;
p <0.001). Post-procedure minimal lumen area (5.73 ± 1.51 vs 4.89 ± 1.38,
p <0.001) and post-procedural acute gain in minimal lumen area (3.60 ± 1.34 vs 2.85 ± 1.25,
p <0.001) were higher in metallic stent group than in BVS group (Table
3). The incidence of definite scaffold thrombosis was 0.6 % in BRS and 0 % in metallic stent group (
p = 1.0). At the end of the first year the incidence of MI was 15 (4 %) in the BRS group and 2 (1 %) patients in the metallic stent group (
p = 0.06), and were mostly non Q-wave MI. There were two scaffold thrombosis, one within 24 h of implantation and the second on the 2nd day [
57]. In the POLAR ACS registry [
58], Absorb BVS was implanted in selected patients with unstable angina, non ST-elevated myocardial infarction (NSTEMI) and ST-elevated myocardial infarction (STEMI). 100 patients were followed up for 1 year with two MACE reported, namely periprocedural MI. At the very least this small registry demonstrated the potential feasibility of the Absorb BVS in the treatment of ACS [
58].
Table 3
Angiographic and IVUS/IVUS-VH outcomes of ABSORB II trial
Angiographic analysis | | | | |
Lesion length obstruction (mm) | 13.8 (6.5) | 13.8 (6.6) | 0.00 (−1.18, 1.18) | 1.00 |
Total scaffolded/stented length (mm) | 21.1 (8.8) | 20.9 (7.4) | 0.24 (−1.17, 1.65) | 0.74 |
Reference vessel diameter | | | | |
Pre-procedure diameter (mm) | 2.59 (0.38) | 2.63 (0.40) | −0.03 (−0.10, 0.04) | 0.36 |
Postprocedure diameter (mm) | 2.64 (0.36) | 2.80 (0.34) | −0.16 (−0.22, −0.09) | <0.001 |
Minimum lumen diameter | | | | |
Pre-procedure diameter (mm) | 1.07 (0.32) | 1.05 (0.32) | 0.02 (−0.03, 0.08) | 0.44 |
Post-procedure in-stent or in-scaff old diameter (mm) | 2.22 (0.33) | 2.50 (0.33) | −0.28 (−0.34, −0.22) | <0.001 |
In-stent/in-scaff old acute gain (mm) | 1.15±0.38 | 1.46±0.38 | −0.30 (−0.37, −0.24) | <0.001 |
Diameter stenosis | | | | |
Pre-procedure percent diameter stenosis (%) | 59±11 % | 60±12 % | −1.07 (−3.11, 0.97) | 0.30 |
Post-procedure in-stent/in-scaffold diameter stenosis (%) | 16±7 % | 10±5 % | 5.37 (4.38, 6.36) | <0.001 |
Pre-procedural fibrotic tissue (%) | 31.47±11.39 | 30.62±11.42 | 0.85 (−1.33, 3.04) | 0.44 |
Pre-procedural fibrofatty tissue (%) | 47.43±16.91 | 48.55±16.86 | −1.12 (−4.35, 2.11) | 0.50 |
Pre-procedural necrotic core (%) | 16.20±6.86 | 16.15±6.90 | 0.05 (−1.27, 1.37) | 0.94 |
Pre-procedural dense calcium (%) | 4.90±4.73 | 4.68±4.10 | 0.22 (−0.61, 1.05) | 0.60 |
Vessel area | | | | |
Pre-procedure area (mm2) | 11.51±3.40 | 12.34±3.42 | −0.83 (−1.47, −0.19) | 0.02 |
Post-procedure area (mm2) | 13.17±3.55 | 14.28±3.59 | −1.11 (−1.78, −0.44) | 0.001 |
Plaque area | | | | |
Pre-procedure plaque area (mm2) | 6.67±2.52 | 7.30±2.68 | 0.6 (−1.12, 0.13) | 0.01 |
Post-procedure plaque area (mm2) | 7.11±2.46 | 7.43±2.44 | −0.32 (−0.78, 0.14) | 0.18 |
Mean lumen area | | | | |
Pre-procedure mean lumen area (mm2) | 4.84±1.39 | 5.02±1.47 | −0.19 (−0.47, 0.08) | 0.16 |
Post-procedure mean lumen area (mm2) | 6.06±1.44 | 6.85±1.60 | −0.80 (−1.09, −0.50) | <0.001 |
Minimal lumen area | | | | |
Pre-procedure minimal lumen area (mm2) | 2.04±0.72 | 2.13±0.83 | −0.10 (−0.25, 0.05) | 0.20 |
Post-procedure minimal lumen area (mm2) | 4.89±1.38 | 5.73±1.51 | −0.84 (−1.12, −0.57) | <0.001 |
Acute gain in minimal lumen area (mm2) | 2.85±1.25 | 3.60±1.34 | −0.75 (−0.99, −0.50) | <0.001 |