Thin Strut CoCr Biodegradable Polymer Biolimus A9-Eluting Stents versus Thicker Strut Stainless Steel Biodegradable Polymer Biolimus A9-Eluting Stents: Two-Year Clinical Outcomes

Background. While thinner struts are associated with improved clinical outcomes in bare-metal stents (BMS), reducing strut thickness may affect drug delivery from drug-eluting stents (DES) and there are limited data comparing otherwise similar thin and thick strut DES. We assessed 2-year outcomes of patients treated with a thin strut (84–88um) cobalt-chromium, biodegradable polymer, Biolimus A9-eluting stent (CoCr-BP-BES) and compared these to patients treated with a stainless steel, biodegradable polymer, Biolimus A9-eluting stent (SS-BP-BES). Methods. In total, 1257 patients were studied: 400 patients from 12 centres receiving ≥1 CoCr-BP-BES in the prospective Biomatrix Alpha registry underwent prespecified comparison with 857 patients who received ≥1 Biomatrix Flex SS-BP-BES in the LEADERS study (historical control). The primary outcome was major adverse cardiac events (MACE)—cardiac death, myocardial infarction (MI), or clinically driven target vessel revascularization (cd-TVR). Propensity analysis was used to adjust for differences in baseline variables and a landmark analysis at day-3 to account for differences in periprocedural MI definitions. Results. MACE at 2 years occurred in 6.65% CoCr-BP-BES versus 13.23% SS-BP-BES groups (unadjusted HR 0.48 [0.31–0.73]; P = 0.0005 ). Following propensity analysis, 2-year adjusted MACE rates were 7.4% versus 13.3% (HR 0.53 [0.35–0.79]; P = 0.004 ). Definite or probable stent thrombosis, adjudicated using identical criteria in both studies, occurred less frequently with CoCr-BP-BES (1.12% vs. 3.22%; adjusted HR 0.32 [0.11–0.9]; P = 0.034 ). In day-3 landmark analysis, the difference in 2-year MACE was no longer significant but there was a lower patient-orientated composite endpoint (11.7% vs. 18.4%; HR 0.6 [0.43–0.83]; P = 0.006 ) and a trend to lower target vessel failure (5.8% vs. 9.1%; HR 0.63 [0.4–1.00]; P = 0.078 ). Conclusion. At 2-year follow-up, propensity-adjusted analysis showed the thin strut (84–88um) Biomatrix Alpha CoCr-BP-BES was associated with improved clinical outcomes compared with the thicker strut (114–120um) Biomatrix Flex SS-BP-BES.

Comparison Between Optical Frequency Domain Imaging and Intravascular Ultrasound for Percutaneous Coronary Intervention Guidance in Biolimus A9-Eluting Stent Implantation

Background: Given the characteristic differences between intravascular ultrasound (IVUS) and optical frequency domain imaging (OFDI), their approach to therapeutic guidance during percutaneous coronary interventions (PCIs) and arterial healing response after stenting may also vary. Methods: MISTIC-1 (The Multimodality Imaging Study in Cardiology cohort 1) is a multicenter, randomized-controlled, noninferiority trial that compared imaging end points between OFDI- and IVUS-guided PCI. Patients with stable coronary artery disease were randomly assigned to either OFDI- or IVUS-guided PCI using a Biolimus A9-eluting stent according to a prespecified protocol for imaging guidance. Stent sizing was based on external elastic lamina in IVUS-guided PCI while lumen up-size in OFDI-guided PCI. Postprocedural OFDI was investigated regardless of randomization, while operators in IVUS-guided PCI arm were blinded to the images. The primary end point was in-segment minimum lumen area assessed using OFDI at 8 months, while the secondary end point was a composite of cardiovascular mortality, target-vessel myocardial infarction, or target-lesion revascularization (device-oriented composite end point). Patients were followed up to 3 years after the index procedure. Results: A total of 109 patients (mean age 70 years, male 78%) with 126 lesions were enrolled. Postprocedural minimum stent area was 6.31±1.89 and 6.72±2.08 mm 2 in OFDI and IVUS group, respectively ( P =0.26). At the 8-month follow-up, in-segment minimum lumen area was 4.56±1.94 and 4.13±1.86 mm 2 in OFDI and IVUS group, respectively ( P non-inferiority <0.001). Both groups had comparable neointimal healing score (median 0.16 [interquartile range, 0.00–3.14] versus 0.90 [0.00–3.30], respectively; P =0.43). The incidence rate of device-oriented composite end point at 3 years was 7.4% and 7.3% in OFDI and IVUS group, respectively (hazard ratio, 1.05 [95% CI, 0.26–4.18]; P =0.95). Conclusions: OFDI-guided PCI was not inferior to IVUS-guided PCI in terms of in-segment minimum lumen area at 8 months. Although a small sample size was acknowledged, OFDI could be an alternative to IVUS when considering intracoronary imaging-guided PCI in selected populations with coronary artery diseases. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03292081.

Similar degree of intimal coverage and apposition among drug-eluting stents with persistent, absorbable or without polymer at 1 and 6 months after implantation

Background Despite technological advances in drug-eluting stents (DES) design, delayed vascular healing is still a problem, triggered by the polymers among others. This may induce restenosis and thrombosis. The development of biodegradable polymers and DES without polymer is thought to improve the vascular response and enhance earlier neointimal healing. Optical coherence tomography (OCT) is the best intracoronary imaging tool to evaluate endothelial coverage after stent implantation. Purpose We aimed to quantitatively assess the differences on intimal coverage between biodegradable-polymer, durable-polymer and without-polymer DES at 1 and 6-month follow-up OCT. Methods A total of 94 patients with de novo coronary lesions were treated with DES: 26% were treated with Biolimus A9 (BA9) stent without polymer, 30% were treated with Everolimus DES with biodegradable polymer (EESb) and 44% with Everolimus DES with persistent polymer (EESp). OCT analysis was performed blindly at an independent Core Lab at three stages: implantation, after one month and after six months. The primary endpoint was to compare neointimal coverage and apposition of these three different types of DES with OCT at one and six months after implantation. Results A total of 16034 struts were analysed (24% BA9, 29% EESb and 47% EESp). No significant differences were found among the groups regarding baseline clinical characteristics. When studying the strut coverage, it is remarkable the relatively low percentage of early neointimal coverage with no significant differences among stents one month after implantation (84–87%). After six months, there was better coverage in the three stent groups compared with one month (p&lt;0.001). The stents without polymer had better neointimal coverage at six months compared with the stents with persistent polymer (99% vs 92%, p=0.0002). No significant differences were found in the strut apposition after one or six months among the three stent types. However, the rate of apposition was higher after six months compared with one month in all stent groups (p=0,001). No significant differences were found in the neointimal hyperplasia at one month among the three stent groups. At six months there was a higher hyperplasia in the stent without polymer compared to the stent with persistent polymer (164μm vs 92μm, p=0,003). The degree of hyperplasia after six months was higher compared to one month in all groups (p=0,001). Conclusions The new-generation DES with biodegradable-polymer or without polymer showed relatively poor early neointimal coverage and similar to the last generation durable-polymer EES. According to these results, DAPT may not be shortened in any of the three DES types studied. Funding Acknowledgement Type of funding source: None

Comparison between optical frequency domain imaging and intravascular ultrasound in PCI guidance for Biolimus A9 eluting stent implantation

Background It has been reported that intravascular ultrasound (IVUS) guided PCI reduced a risk of major adverse cardiac event compared to conventional angiography guided PCI, while comparison between IVUS-guided and optical frequency domain imaging (OFDI)-guided PCI specifically in long-term clinical outcomes (&gt;1 year) has been unexplored. Purpose We sought to compare imaging surrogates at 8 months and clinical outcomes beyond 1 year after drug-eluting stent implantation between IVUS and OFDI guidance. Methods The MISTIC-1 is a prospective, multi-centre, single-blinded, randomised-controlled, non-inferiority trial comparing OFDI-guided and IVUS-guided PCI using Biolimus A9 eluting Nobori stent. We enrolled patients with stable coronary artery disease who have symptoms or clinically relevant myocardial ischemia. Stent landing zones were selected in the most normal looking sites with largest lumen and without percentage plaque area &gt;50% in IVUS group while without lipidic plaque of &gt;2 quadrants or suggestive thin-cap fibroatheroma in OFDI group. Stent sizing was based on external elastic lamina (EEL) in IVUS group, while by taking 10% or 0.25mm larger than mean lumen diameter at reference sites in OFDI group. Stent optimisation with in-stent minimum lumen area ≥80% of the average lumen area at proximal and distal reference sites was encouraged in both groups. Primary efficacy endpoint is in-segment minimum lumen area (MLA) assessed by OFDI at 8 months. Secondary safety endpoint is a composite of cardiovascular death, target vessel myocardial infarction, or target lesion revascularisation. Based on the assumption that mean in-segment MLA at follow-up was 4.5mm2 with a standard deviation of 2.0mm2 in the control (IVUS) group and a non-inferiority limit of 1.2mm2 for OFDI group, sample size was estimated as 48 cases in each group with 5% type I error and 90% statistical power. Results Since June-2014 and August-2016, we prospectively enrolled 109 patients (mean age 70 years, male 78%) with 126 lesions. Baseline patient and lesion characteristics were well balanced and average nominal size and length of stent used did not differ between OFDI-guided and IVUS-guided PCI (3.0 and 19.1mm vs. 3.1 and 19.3mm, respectively). Post-procedural minimum stent area was 6.24mm2 in OFDI group and 6.72mm2 in IVUS group (p=0.20). At 8-month follow-up, in-segment MLA was 4.56mm2 in OFDI group and 4.13mm2 in IVUS group (P for non-inferiority &lt;0.001). During the follow-up (median 4.5 years [1654 days]), incidence rates of major adverse cardiac event were comparable between the two groups (7.4% in OFDI group and 7.3% in IVUS group, hazard ratio 0.96, 95% CI 0.24–3.83, p=0.95). No definite or probable stent thrombosis were documented in both groups. Conclusion OFDI-guided PCI demonstrated comparable results in achieving satisfactory imaging surrogates as well as long-term clinical outcomes after newer generation DES implantation as compared to IVUS-guided PCI. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Suzuken Memorial Foundation

Angioscopic evaluation of vascular healing at 1 and 12 months after drug-coated stent implantation

Background Polymer- and carrier-free Biolimus-A9-coated stent (DCS) is expected better vascular healing compared with conventional durable polymer drug-eluting stents (DES). Moreover, DCS had been demonstrated in clinical trials to allow one-month short dual antiplatelet therapy, which might achieve sufficient healing at only 1 month after implantation. However, the process of vascular healing after DCS implantation has not been elucidated by angioscopic observation. Purpose To evaluate the process of vascular healing at 1 month and 12 months after DCS implantation. Methods This study included 57 patients treated with DCS or durable polymer everolimus-eluting stents (EES) in our hospital from April 2017 to April 2019. Firstly, the angioscopic findings of DCS at 1 month (n=16) and 12 months (n=14) after implantation were respectively compared with EES at 12 months after implantation (EES-12, n=35) as a standard healing status of DES. Secondary, angioscopic findings of DCS at 1 month and 12 months after implantation were compared among the serially observed eight patients. Neointimal coverage (NIC) grade, yellow colour grade, and the presence of thrombus were evaluated. NIC grade was classified as grade 0 (no neointimal coverage), grade 1 (struts were bulged into lumen but covered), grade 2 (struts were embedded in the neointima but visible), or grade 3 (struts were fully embedded and invisible). Yellow colour grade was classified as grade 0 (white), grade 1 (light yellow), grade 2 (yellow), or grade 3 (intensive yellow). Results At 1 month after DCS implantation, dominant NIC grade was lower (0.3±0.5 vs. 1.5±0.7, p&lt;0.001) and the frequency of thrombus was higher (38% vs. 6%, p=0.008) than EES-12. On the other hands, at 12 months after DCS implantation, dominant NIC grade was higher (2.1±0.6 vs. 1.5±0.7, p=0.013) and the frequency of thrombus was not different (7% vs. 6%, p=1.000) in comparison with EES-12. By serial observation of DCS, dominant NIC grade was higher at 12 months than at 1 month (2.3±0.5 vs. 0.4±0.5, p&lt;0.001), while yellow colour grade (1.0±0.5 vs. 1.5±1.2, p=0.227) and the frequency of thrombus adhesion (0% vs. 38%, p=0.200) were not different. Conclusion Compared with EES-12, vascular healing of DCS was inferior at 1 month but superior at 12 months. Figure 1 Funding Acknowledgement Type of funding source: None