Histopathologic response after hydrophilic polyethylene glycol-coating stent and hydrophobic octadecylthiol-coating stent implantations in porcine coronary restenosis model.

Device-related problems of drug-eluting stents, including stent thrombosis related to antiproliferative drugs and polymers, can cause adverse events such as inflammation and neointimal hyperplasia. Stent surface modification, wherein the drug and polymer are not required, may overcome these problems. We developed hydrophilic polyethylene glycol (PEG)-coating and hydrophobic octadecylthiol (ODT)-coating stents without a drug and polymer and evaluated their histopathologic response in a porcine coronary restenosis model. PEG-coating stents (n = 12), bare-metal stents (BMS) (n = 12), and ODT-coating stents (n = 10) were implanted with oversizing in 34 porcine coronary arteries. Four weeks later, the histopathologic response, arterial injury, inflammation, and fibrin scores were analyzed. A p value < 0.05 was considered statistically significant. There were significant differences in the internal elastic lamina area, lumen area, neointimal area, percent area of stenosis, arterial injury score, inflammation score, and fibrin score among the groups. Compared to the BMS or ODT-coating stent group, the PEG-coating stent group had significantly increased internal elastic lamina and lumen area (all p < 0.001) and decreased neointimal area and percent area of stenosis (BMS: p = 0.03 and p < 0.001, respectively; ODT-coating: p = 0.013 and p < 0.001, respectively). Similarly, the PEG-coating group showed significantly lower inflammation and fibrin scores than the BMS or ODT-coating groups (BMS: p = 0.013 and p = 0.007, respectively; ODT-coating: p = 0.014 and p = 0.008, respectively). In conclusion, hydrophilic PEG-coating stent implantation was associated with lower inflammatory response, decreased fibrin deposition, and reduced neointimal hyperplasia than BMS or hydrophobic ODT-coating stent implantation in the porcine coronary restenosis model.

Long-Term Comparison of Platinum Chromium Everolimus-Eluting Stent vs. Cobalt Chromium Zotarolimus-Eluting Stent　- 3-Year Outcomes From the HOST-ASSURE Randomized Clinical Trial.

BACKGROUND: There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).Methods and Results:A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730-1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677). CONCLUSIONS: PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.

BioMatrix Versus Orsiro Stents for Coronary Artery Disease: A Multicenter, Randomized, Open-Label Study.

BACKGROUND: Comparative studies of ultrathin-strut biodegradable polymer sirolimus-eluting stent (BP-SES) have reported promising results and validated its excellent outcomes in terms of safety and efficacy. However, there are limited studies comparing BP drug-eluting stents with struts of different thicknesses. We compared the long-term clinical outcomes of patients treated with an ultrathin-strut BP-SES or a thick-strut biodegradable polymer biolimus-eluting stent (BP-BES). METHODS: The BIODEGRADE trial (Biomatrix and Orsiro Drug-Eluting Stents in Angiographic Result in Patients With Coronary Artery Disease) is a multicenter prospective randomized study comparing coronary revascularization in patients with ultrathin-strut BP-SES and thick-strut BP-BES with the primary end point of target lesion failure at 18 months posttreatment. We performed the prespecified analysis of 3-year clinical outcomes. RESULTS: In total, 2341 patients were randomized to receive treatment with ultrathin-strut BP-SES (N=1175) or thick-strut BP-BES (N=1166). The 3-year incidence rate of target lesion failure was 3.2% for BP-SES and 5.1% for BP-BES (P=0.023). The difference was primarily due to differences in ischemia-driven target lesion revascularization (BP-SES, 1.5%; BP-BES, 2.8%; P=0.035) between groups. A landmark analysis of the late follow-up period showed significant differences in target lesion failure, with outcomes being better in BP-SES. Cardiac death and target lesion revascularization were significantly lower in the BP-SES group. CONCLUSIONS: In a large, randomized trial, the long-term clinical outcome of target lesion failure at 3 years was significantly better among patients treated with the ultrathin-strut BP-SES. The results indicate the superiority of the ultrathin-strut BP-SES compared with the thick-strut BP-BES. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02299011.

BioMatrix versus Orsiro biodegradable polymer stents in all-comer patients with coronary artery disease: the multicentre, randomised BIODEGRADE trial.

AIMS: The aim of this trial was to compare the safety and efficacy of a thin-strut biodegradable polymer sirolimus-eluting cobalt-chromium stent (Orsiro) to a thick-strut biodegradable polymer biolimus-eluting stent (BioMatrix). METHODS AND RESULTS: This randomised, open-label, non-inferiority trial was conducted among patients undergoing percutaneous coronary intervention. The primary endpoint was target lesion failure (TLF). Between July 2014 and September 2017, we randomly assigned 2,341 patients to BioMatrix stents (n=1,166) or Orsiro stents (n=1,175). We analysed 2,327 patients who completed 18-month follow-up. The mean patient age was 63.5 years, and 1,565 (67.3%) patients presented with acute coronary syndrome. At 18 months, 34 (2.9%) patients with BioMatrix stents and 24 (2.1%) with Orsiro stents experienced TLF (hazard ratio [HR] 0.70, upper limit of one-sided 95% confidence interval: 1.18, p for non-inferiority <0.0001). No significant differences were noted in rates of cardiac death (16 [1.4%] vs 12 [1.0%], p=0.558), target lesion-related myocardial infarction (0 [0%] vs 3 [0.3%], p=0.250), target lesion revascularisation (18 [1.6%] vs 10 [0.9%], p=0.124), or stent thrombosis (0 [0%] vs 2 [0.2%], p=0.50). CONCLUSIONS: In patients with a high prevalence of acute coronary syndrome, Orsiro stents were not inferior to BioMatrix stents. Both showed good clinical outcomes.

Long-Term Outcomes of Biodegradable Versus Second-Generation Durable Polymer Drug-Eluting Stent Implantations for Myocardial Infarction.

OBJECTIVES: This study sought to compare outcomes between biodegradable polymer drug-eluting stent (BP-DES) and second-generation durable polymer drug-eluting stent (DP-DES) implantations for acute myocardial infarction (MI) using a nationwide dataset. BACKGROUND: Data regarding outcomes of BP-DES versus second-generation DP-DES are inconclusive. METHODS: Among 13,104 patients with acute MI in a nationwide registry who underwent percutaneous coronary intervention (November 2011 to December 2015), BP-DES and second-generation DP-DES were implanted in 2,261 (21.7%) and 8,182 patients (78.3%), respectively. Major adverse cardiac events (MACE) (all-cause death, recurrent MI, or any revascularization) were compared in multivariable Cox regression, propensity score (PS) matched, and underwent PS-adjusted analyses. RESULTS: MACE occurred in 1,492 (14.3%) patients during a median 723-day follow-up. MACE were less frequent with BP-DES implantation than with second-generation DP-DES implantation (entire cohort hazard ratio [HR]: 0.845; 95% confidence interval [CI]: 0.740 to 0.965; PS-matched HR: 0.669; 95% CI: 0.550 to 0.814). Risk of all-cause death (entire cohort HR: 0.831; 95% CI: 0.692 to 0.997; PS-matched HR: 0.752; 95% CI: 0.495 to 0.931), cardiac death (entire cohort HR: 0.685; 95% CI: 0.542 to 0.865; PS-matched HR: 0.613; 95% CI: 0.463 to 0.872), recurrent MI (entire cohort HR: 0.662; 95% CI: 0.466 to 0.941; PS-matched HR: 0.611; 95% CI: 0.427 to 0.898), and heart failure readmission (entire cohort HR: 0.625; 95% CI: 0.447 to 0.875; PS-matched HR: 0.584; 95% CI: 0.385 to 0.887) was less with BP-DES implantation. There were no significant group differences in the incidences of any revascularization, stroke, and definite or probable stent thrombosis. CONCLUSIONS: In patients with acute MI who underwent percutaneous coronary intervention, BP-DES implantation is associated with improved outcomes compared with second-generation DP-DES implantation.

Outcomes of Acute Myocardial Infarction Patients Implanted With Biodegradable Polymer Biolimus-Eluting Stents Versus New-Generation Durable Polymer Drug-Eluting Stents: A Retrospective Analysis.

We compared outcomes between biodegradable polymer biolimus-eluting stent (BP-BES) and new-generation durable polymer drug-eluting stent (DP-DES) implantations in patients with acute myocardial infarction (MI). Among 13472 patients with acute MI in a nationwide registry, 557 (64.8%) were in the BP-BES and 303 (35.2%) in the new-generation DP-DES group following coronary reperfusion. The occurrence of major adverse cardiac events (MACE; death, MI, revascularization) and stent thrombosis was compared. Major adverse cardiac events occurred in 53 (6.2%) patients and showed similar rates between the BP-BES and new-generation DP-DES groups (all: 6.6% vs 5.9%, P = .652; propensity score [PS] matched: n = 380, 6.3% vs 5.3%, P = .623). Stent thrombosis did not differ between groups (all: 0.3% vs 0.4%, P = .892; PS matched: 0.5% vs 0.5%, P = 1.000). Major adverse cardiac event-free survival was comparable between groups (all: 93.4% vs 94.1%, log-rank P = .357; PS matched: 93.7% vs 94.7%, log-rank P = .445). Biodegradable polymer biolimus-eluting stent was not associated with MACE (all: hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.75-3.74; P = 0.212; PS matched: HR, 1.05; 95% CI, 0.40-2.75; P = .915). In conclusion, in patients with acute MI, BP-BES was equivalent to the new-generation DP-DES in terms of outcomes.

Predictors and Long-Term Clinical Outcome of Longitudinal Stent Deformation: Insights From Pooled Analysis of Korean Multicenter Drug-Eluting Stent Cohort.

BACKGROUND: There are limited data on the frequency of and factors associated with quantitative coronary angiography (QCA)-defined longitudinal stent deformation (LSD) in various contemporary drug-eluting stents platforms. This study sought to evaluate the predictors of LSD and its long-term clinical implication. METHODS AND RESULTS: A patient-level pooled analysis was performed with 7350 lesions in 5871 patients treated with platinum-chromium-based everolimus-eluting stent (Promus Element), cobalt-chromium-based everolimus-eluting stent (Promus/Xience V), or cobalt-chromium-based zotarolimus-eluting stent (Endeavor Resolute). QCA was performed to analyze differences of stent length between immediate post-deployment and final post-procedure. Independent factors associated with LSD were identified. Clinical outcomes at 3 years were compared between those with and without QCA-based LSD. The frequency of QCA-based LSD was 1.12% (82 cases). Nine of these cases were angiographically overt. Left main or ostial lesion, bifurcation treatment with provisional side branch stenting or ballooning, additional downstream intervention of a distal lesion, intravascular ultrasound use, and adjunctive post-dilatation were independently associated with QCA-based LSD. The type of stent was not associated with QCA-based LSD. Rates of target lesion failure were nominally higher in lesions with QCA-based LSD than in those without (8.97% versus 5.88%; hazard ratio, 1.415; 95% confidence interval, 0.631-3.175; P=0.399). CONCLUSIONS: LSD is uncommon with contemporary drug-eluting stents, regardless of the type of stent platform. LSD is mainly associated with procedural factors, especially with additional downstream procedures which require the passage of devices through the stent. Careful manipulation of poststent imaging or procedural devices is required to prevent LSD. More data are needed to clarify the impact of LSD on clinical events.

Harmonizing Optimal Strategy for Treatment of coronary artery diseases--comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS RCT): study protocol for a randomized controlled trial.

BACKGROUND: Antiplatelet treatment is an important component in optimizing the clinical outcomes after percutaneous coronary intervention (PCI) especially in patients with acute coronary syndrome (ACS). Prasugrel, which is a new P2Y12 inhibitor, has been confirmed as efficacious in a large trial in Western countries, and a similar trial is also to be launched in Asian countries. Although a 60-mg loading dose of prasugrel followed by 10 mg per day should be acceptable, there have been no data regarding the optimal dose in Asian patients. Furthermore, serum levels of prasugrel and the rates of platelet inhibition are known to be higher in Asians than Caucasians with the same dose of the drug. Polymer, a key component of drug-eluting stents (DES), has been suggested as the cause of inflammation leading to late complications, and has driven many companies to develop biodegradable-polymer DES. Currently, there are limited data regarding the head-to-head comparison between BP-BES and the biostable polymer CoCr-EES or the newest platinum-chromium everolimus-eluting stent (PtCr-EES). Furthermore, the polymer issue may be more important in ACS where there is ruptured thrombotic plaque where polymer-induced inflammation may affect the local milieu of the stented artery. Therefore, the present study dedicated only to ACS patients, will offer important information on the optimal prasugrel dose in the Asian population by comparing a 10-mg versus a 5-mg maintenance dose beyond 1 month after PCI, as well as giving important insight into the polymer issue by comparing BP-BES versus biostable-polymer PtCr-EES. METHOD/DESIGN: Harmonizing Optimal Strategy for Treatment of coronary artery diseases--comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS) trial is a multicenter, randomized and open-label clinical study with a 2 × 2 factorial design, according to the type of stent (PtCr-EES versus BP-BES) and prasugrel maintenance dose (5 mg versus 10 mg), to demonstrate non-inferiority of PtCr-EES relative to BP-BES or the reduced prasugrel dose relative to conventional dose in an Asian all-comers PCI population presenting with ACS. Approximately 3400 patients will undergo prospective, random assignment separately to either stent or prasugrel arm (1:1 ratio, respectively). When the patients have contraindications to prasugrel, they are categorized into an antiplatelet observation group after stent-randomization. The primary endpoint is the patient-oriented composite outcome, which is a composite of all-cause mortality, any myocardial infarction (MI), any repeat revascularization in the stent arm at 12 months after index PCI. In the prasugrel arm, primary endpoint is any major adverse cardiovascular event, which is a composite of all-cause mortality, any MI, any stent thrombosis (Academic Research Consortium (ARC)-defined), any repeat revascularization, stroke, or bleeding (BARC class ≥ 2). DISCUSSION: The HOST-REDUCE-POLYTECH-ACS RCT is the first study exploring the optimal maintenance dose of prasugrel beyond 1 month after PCI for ACS in Asian all-comers. In addition, this is the largest study dedicated only to ACS patients to evaluate the polymer issue in the situation of ACS by directly comparing biostable-polymer PtCr-EES versus BP-BES. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT02193971, 13 July 2014).

A randomized comparison of platinum chromium-based everolimus-eluting stents versus cobalt chromium-based Zotarolimus-Eluting stents in all-comers receiving percutaneous coronary intervention: HOST-ASSURE (harmonizing optimal strategy for treatment of coronary artery stenosis-safety & effectiveness of drug-eluting stents & anti-platelet regimen), a randomized, controlled, noninferiority trial.

OBJECTIVES: This study sought to test whether the newly developed platinum chromium (PtCr)-based everolimus-eluting stent (EES) is noninferior to the cobalt chromium (CoCr)-based zotarolimus-eluting stent (ZES) in all-comers receiving percutaneous coronary intervention (PCI). BACKGROUND: PtCr provides improved radial strength, conformability, and visibility compared with the CoCr alloy, but PtCr-based stents have not been tested in a wide range of patients receiving PCI. Also, recent case series have raised the issue of longitudinal stent deformation (LSD) with newer drug-eluting stents. METHODS: We randomly assigned 3,755 all-comers receiving PCI to PtCr-EES or CoCr-ZES. The primary outcome was target lesion failure (TLF) at 1-year post-PCI, defined as the composite of cardiac death, nonfatal target vessel-related myocardial infarction, and ischemia-driven target lesion revascularization. Post-hoc angiographic analysis was performed to qualitatively and quantitatively analyze LSD. RESULTS: At 1 year, TLF occurred in 2.9% and 2.9% of the population in the PtCr-EES and CoCr-ZES groups, respectively (superiority p = 0.98, noninferiority p = 0.0247). There were no significant differences in the individual components of TLF as well as the patient-oriented clinical outcome. Of 5,010 stents analyzed, LSD occurred in 0.2% and 0% in the PtCr-EES and CoCr-ZES groups, respectively (p = 0.104). There was no significant difference in post-deployment stent length ratio between the 2 stents (p = 0.352). CONCLUSIONS: At 1 year, PtCr-EES was noninferior to CoCr-ZES in all-comers receiving PCI. Although LSD was observed only in PtCr-EES, both the stent length ratio and the frequency of LSD were not significantly different between the 2 stent types, and PtCr-EES was not associated with adverse clinical outcomes. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [HOST-ASSURE]; NCT01267734).

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial.

BACKGROUND: Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients. METHODS: In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. DISCUSSION: The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. TRIAL REGISTRATION: ClincalTrials.gov number NCT01267734.