Differential impact of abluminal groove-filled biodegradable-polymer sirolimus-eluting stent versus durable-polymer everolimus-eluting stent on and off dual antiplatelet therapy.

BACKGROUND: Current guidelines recommend dual antiplatelet therapy (DAPT) following percutaneous coronary intervention for 6-12 months in patients with acute coronary syndrome (ACS) and 3-6 months in those with chronic coronary syndromes (CCS). Whether DAPT duration has a differential effect on outcomes following treatment of ischemic coronary disease with durable versus biodegradable drug-eluting stent (DES) is poorly defined. METHODS: The TARGET All Comer study was a randomized trial of patients with ischemic coronary artery disease assigned to treatment with either a biodegradable polymer DES (Firehawk) or a durable polymer DES (XIENCE). This pre-specified TARGET AC sub-analysis sought to evaluate the 2-year clinical outcomes before and after DAPT discontinuation. The primary endpoint was target lesion failure (TLF). RESULTS: A total of 1,296 (78.4%) of 1,653 randomized patients were included in this substudy, of which 1,210 (93.4%) remained on DAPT at 6 months, 863 (66.6%) at 12 months, and 409 (31.6%) at 2 years. There was no difference in TLF between patients treated with Firehawk and XIENCE stents from index procedure to DAPT discontinuation (8.0 and 7.7%, p > .99) or after DAPT discontinuation (2.9 vs. 3.8%, p = .16). After DAPT discontinuation, target vessel myocardial infarction (1.3 vs. 3.3%, p = .07), and ischemia-driven target lesion revascularization (0.5 vs. 1.9%, p = .06) favored treatment with Firehawk. CONCLUSIONS: Although TLF was comparable for both Firehawk and XIENCE stent groups before and after DAPT discontinuation, after DAPT discontinuation, there was a trend for less target vessel myocardial infarction and ischemia-driven revascularization with the biodegradable polymer DES.

Five-year clinical outcomes and intracoronary imaging findings of the COMFORTABLE AMI trial: randomized comparison of biodegradable polymer-based biolimus-eluting stents with bare-metal stents in patients with acute ST-segment elevation myocardial infarction.

AIMS: The long-term outcomes of biolimus-eluting stents (BESs) with biodegradable polymer as compared with bare-metal stent (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain unknown. METHODS AND RESULTS: We performed a 5-year clinical follow-up of 1157 patients (BES: N = 575 and BMS: N = 582) included in the randomized COMFORTABLE AMI trial. Serial intracoronary imaging of stented segments using both intravascular ultrasound (IVUS) and optical coherence tomography performed at baseline and 13 months follow-up were analysed in 103 patients. At 5 years, BES reduced the risk of major adverse cardiac events [MACE; hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.39-0.79, P = 0.001], driven by lower risks for target vessel-related reinfarction (HR 0.44, 95% CI: 0.22-0.87, P = 0.02) and ischaemia-driven target lesion revascularization (HR 0.41, 95% CI: 0.25-0.66, P < 0.001). Definite stent thrombosis (ST) was recorded in 2.2% and 3.9% (HR 0.57, 95% CI: 0.28-1.16, P = 0.12) with no differences in rates of very late definite ST (1.3% vs. 1.6%, P = 0.77). Optical coherence tomography showed no difference in the frequency of malapposed stent struts at follow-up (BES 0.08% vs. BMS 0.02%, P = 0.10). Uncovered stent struts were rarely observed but more frequent in BES (2.1% vs. 0.15%, P < 0.001). In the IVUS analysis, there was no positive remodelling in either group (external elastic membrane area change BES: -0.63 mm2, 95% CI: -1.44 to 0.39 vs. BMS -1.11 mm2, 95% CI: -2.27 to 0.04, P = 0.07). CONCLUSION: Compared with BMS, the implantation of biodegradable polymer-coated BES resulted in a lower 5-year rate of MACE in patients with STEMI undergoing primary percutaneous coronary intervention. At 13 months, vascular healing in treated culprit lesions was almost complete irrespective of stent type. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00962416.

Self-expandable sirolimus-eluting stents compared to second-generation drug-eluting stents for the treatment of the left main: A propensity score analysis from the SPARTA and the FAILS-2 registries.

OBJECTIVES: To compare the effectiveness and safety of self-expandable, sirolimus-eluting Stentys stents (SES) and second-generation drug-eluting stents (DES-II) for the treatment of the unprotected left main (ULM). BACKGROUND: SES may provide a valuable option to treat distal ULM, particularly when significant caliber gaps with side branches are observed. METHODS: Patients from the multicenter SPARTA (clinicaltrials.gov: NCT02784405) and FAILS2 registries were included. Propensity-score with matching was performed to account for the lack of randomization. Primary end-point was the rate of major adverse cardiovascular events (MACE, a composite of all cause death, myocardial infarction, target lesion revascularization [TLR], unstable angina and definite stent thrombosis [ST]). Single components of MACE were the secondary end-points. RESULTS: Overall, 151 patients treated with SES and 1270 with DES-II were included; no differences in MACE rate at 250 days were observed (9.8% vs. 11.5%, P = 0.54). After propensity score with matching, 129 patients treated with SES and 258 with DES-II, of which about a third of female gender, were compared. After a follow-up of 250 days, MACE rate did not differ between the two groups (9.9% vs. 8.5%, P = 0.66), as well as the rate of ULM TLR (1.6% vs. 3.1%, P = 0.36) and definite ST (0.8% vs. 1.2%, P = 0.78). These results were consistent also when controlling for the treatment with provisional vs. 2-stents strategies for the ULM bifurcation. CONCLUSION: SES use for ULM treatment was associated with a similar MACE rate compared to DES-II at an intermediate-term follow-up. SES might represent a potential option in this setting.

Long-Term Percutaneous Coronary Intervention Outcomes in Chronic Versus Acute Coronary Syndromes (TARGET All Comers Trial).

In the Targeted therapy with a localised abluminal coated, low-dose sirolimus-eluting, biodegreadable polymer coronary stent (TARGET; NCT02520180) All Comers trial the biodegradable polymer (BP) sirolimus-eluting FIREHAWK stent was noninferior to the durable polymer (DP) everolimus-eluting XIENCE stent with respect to target lesion failure (TLF) at 1 and 5 years; however, the long-term safety and efficacy in the setting of acute coronary syndromes (ACS) are not known. We sought to assess the long-term outcomes in ACS versus chronic coronary syndromes (CCS) with BP sirolimus-eluting stent (SES) versus DP everolimus-eluting stent (EES). The TARGET AC study was a multicenter, open-label, noninferiority trial of all comer patients randomly allocated 1:1 to BP SES or DP EES (stratified by ST-elevation myocardial infarction and study site). In this predefined substudy, the outcomes were compared based on clinical presentation (ACS vs CCS) and treatment allocation. A total of 1,653 patients were enrolled (728 with ACS and 922 with CCS), with 94% completing the 5-year follow-up. The baseline characteristics were well-matched between the 2 stent types; however, co-morbidities were more prevalent in the CCS than in the ACS population. TLF (15.5% vs 17.7%, p = 0.24), patient-oriented outcomes (32.0% vs 34.4%, p = 0.31), and stent thrombosis (4.1% vs 3.3%, p = 0.40) were similar between patients with ACS and patients with CCS. In the ACS cohort, the outcomes at 5 years for BP SES versus DP EES were similar for TLF (16.0% vs 14.9%, p = 0.70), ischemia-driven target lesion revascularization (5.6% vs 8.3%, p = 0.17), and definite/probable stent thrombosis (2.7% vs 4.6%, p = 0.18). The same was true for the CCS cohort, with 5-year outcomes for BP SES versus DP EES for TLF (18.0% vs 17.4%, p = 0.82), ischemia-driven target lesion revascularization (6.4% vs 5.0%, p = 0.37), and definite/probable stent thrombosis (3.0% vs 1.8%, p = 0.26). In conclusion, in the TARGET AC trial, 1 in 3 patients had a major adverse event at 5 years, irrespective of CCS or ACS presentation. Long-term, the BP sirolimus-eluting FIREHAWK stent was as safe and effective as the DP everolimus-eluting XIENCE stent across the spectrum of clinical presentations.

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable-polymer coronary stent - five-year results of the TARGET All Comers randomised clinical trial.

BACKGROUND: In the prospective, multicentre, randomised TARGET All Comers study, percutaneous coronary intervention (PCI) with the FIREHAWK biodegradable-polymer sirolimus-eluting stent (BP-SES) was non-inferior to the durable-polymer everolimus-eluting stent (DP-EES) for the primary endpoint of target lesion failure (TLF) at 12 months. AIMS: We aimed to report the final study outcomes at 5 years. METHODS: Patients referred for PCI were randomised to receive either a BP-SES or DP-EES in a 1:1 ratio in 10 European countries. Randomisation was stratified by centre and ST-elevation myocardial infarction (STEMI) presentation, and clinical follow-up extended to 5 years. The primary endpoint was TLF (composite of cardiac death, target vessel myocardial infarction [MI], or ischaemia-driven target lesion revascularisation). Secondary endpoints included patient-oriented composite events (POCE; composite of all-cause death, all MI, or any revascularisation and its components). RESULTS: From December 2015 to October 2016, 1,653 patients were randomly assigned to the BP-SES or DP-EES groups, of which 93.8% completed 5-year clinical follow-up or were deceased. At 5 years, TLF occurred in 17.1% of the BP-SES group and in 16.3% of the DP-EES group (p=0.68). POCE occurred in 34.0% of the BP-SES group and 32.7% of the DP-EES group (p=0.58). Revascularisation was the most common POCE, occurring in 19.3% of patients receiving BP-SES and 19.2% receiving DP-EES, of which less than one-third was ischaemia-driven target lesion-related. In the landmark analysis, there were no differences in the rates of TLF and POCE between groups from 1 to 5 years, and these results were consistent across all subgroups. CONCLUSIONS: In an all-comers population requiring stent implantation for myocardial ischaemia, the BP-SES was non-inferior to the DP-EES for the primary endpoint of TLF at 12 months, and results were sustained at 5 years, confirming the long-term safety and efficacy of the FIREHAWK BP-SES.

Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial.

CONTEXT: The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). OBJECTIVE: To compare stents eluting biolimus from a biodegradable polymer with bare-metal stents in primary PCI. DESIGN, SETTING, AND PATIENTS: A prospective, randomized, single-blinded, controlled trial of 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19, 2009, and January 25, 2011. Clinical follow-up was performed at 1 and 12 months. INTERVENTION: Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582). MAIN OUTCOME MEASURES: Primary end point was the rate of major adverse cardiac events, a composite of cardiac death, target vessel-related reinfarction, and ischemia-driven target-lesion revascularization at 1 year. RESULTS: Major adverse cardiac events at 1 year occurred in 24 patients (4.3%) receiving biolimus-eluting stents with biodegradable polymer and 49 patients (8.7%) receiving bare-metal stents (hazard ratio [HR], 0.49; 95% CI, 0.30-0.80; P = .004). The difference was driven by a lower risk of target vessel-related reinfarction (3 [0.5%] vs 15 [2.7%]; HR, 0.20; 95% CI, 0.06-0.69; P = .01) and ischemia-driven target-lesion revascularization (9 [1.6%] vs 32 [5.7%]; HR, 0.28; 95% CI, 0.13-0.59; P < .001) in patients receiving biolimus-eluting stents compared with those receiving bare-metal stents. Rates of cardiac death were not significantly different (16 [2.9%] vs 20 [3.5%], P = .53). Definite stent thrombosis occurred in 5 patients (0.9%) treated with biolimus-eluting stents and 12 patients (2.1%; HR, 0.42; 95% CI, 0.15-1.19; P = .10) treated with bare-metal stents. CONCLUSION: Compared with a bare-metal stent, the use of biolimus-eluting stents with a biodegradable polymer resulted in a lower rate of the composite of major adverse cardiac events at 1 year among patients with STEMI undergoing primary PCI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00962416.

2-Year Clinical Outcomes of an Abluminal Groove-Filled Biodegradable-Polymer Sirolimus-Eluting Stent Compared With a Durable-Polymer Everolimus-Eluting Stent.

OBJECTIVES: The aim of this study was to assess the 2-year clinical outcomes of the Firehawk stent (Shanghai MicroPort Medical Group, Shanghai, China), a novel abluminal groove-filled biodegradable-polymer sirolimus-eluting coronary stent, compared with XIENCE (Abbott Vascular, Santa Clara, California), a durable-polymer everolimus-eluting coronary stent. BACKGROUND: The long-term outcomes of the Firehawk stent have not been evaluated beyond 1 year in a randomized all-comers clinical trial. METHODS: The TARGET All Comers study is a prospective, multicenter, all-comers, randomized, noninferiority trial conducted in Europe. A total of 1,653 patients were randomly assigned to undergo implantation of either the Firehawk or the XIENCE stent. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. RESULTS: At 2-year follow-up, the incidence of target lesion failure was 8.7% in the Firehawk group versus 8.6% in the XIENCE group (p = 0.92). The event rates of individual components of the primary endpoint were comparable for the 2 groups. Landmark analyses between 1- and 2-year follow-up revealed no statistically significant difference of TLF for the Firehawk versus the XIENCE stent. Beyond 1 year, very late definite or probable stent thrombosis occurred in 3 patients (0.4%) in the Firehawk group and in 7 patients (0.9%) in the XIENCE group (p = 0.34). CONCLUSIONS: The 2-year follow-up of the TARGET All Comers study confirms comparable safety and efficacy profiles of the Firehawk and XIENCE stents.

Report of an ESC-EAPCI Task Force on the evaluation and use of bioresorbable scaffolds for percutaneous coronary intervention: executive summary.

A previous Task Force of the European Society of Cardiology (ESC) and European Association of Percutaneous Cardiovascular Interventions (EAPCI) provided a report on recommendations for the non-clinical and clinical evaluation of coronary stents. Following dialogue with the European Commission, the Task Force was asked to prepare an additional report on the class of devices known as bioresorbable scaffolds (BRS). Five BRS have CE-mark approval for use in Europe. Only one device -the Absorb bioresorbable vascular scaffold- has published randomized clinical trial data and this data show inferior outcomes to conventional drug-eluting stents (DES) at 2-3 years. For this reason, at present BRS should not be preferred to conventional DES in clinical practice. The Task Force recommends that new BRS devices should undergo systematic non-clinical testing according to standardized criteria prior to evaluation in clinical studies. A clinical evaluation plan should include data from a medium sized, randomized trial against DES powered for a surrogate end point of clinical efficacy. Manufacturers of successful devices receive CE- mark approval for use and must have an approved plan for a large-scale randomized clinical trial with planned long-term follow-up.

Stent-based delivery of tissue inhibitor of metalloproteinase-3 adenovirus inhibits neointimal formation in porcine coronary arteries.

BACKGROUND: Stent-based antiproliferative therapy appears to decrease in-stent restenosis. However, alternative approaches might produce equivalent efficacy with better long-term safety. In previous work, an adenovirus capable of expressing the tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) inhibited neointima formation in cell cultures and porcine saphenous vein grafts. RAdTIMP-3 decreased smooth muscle cell migration, stabilized the extracellular matrix, and uniquely promoted apoptosis. The current study developed eluting stent technology to deliver RAdTIMP-3 during stenting of pig coronary arteries. METHODS AND RESULTS: Binding of virus to and elution from stents and transduction of pig coronary arteries were confirmed using beta-galactosidase as a reporter gene in vitro and in vivo. Deployment of RAdTIMP-3-coated stents increased apoptosis and reduced neointimal cell density, but did not increase inflammation or proliferation compared with beta-galactosidase-expressing adenovirus (RAdlacZ). Neointimal area after 28 days was significantly reduced to 1.27+/-0.19 mm2 with RAdTIMP-3 versus 2.61+/-0.31 mm2 with RAdlacZ stents (P<0.001) and 2.12+/-0.20 mm2 with bare stents (P<0.005). CONCLUSIONS: Our results demonstrate for the first time to our knowledge the feasibility of adenovirus-coated stent technology and highlight the potential of TIMP-3 to produce significant inhibition of in-stent neointima formation.

Safety and performance of a novel embolic deflection device in patients undergoing transcatheter aortic valve replacement: results from the DEFLECT I study.

AIMS: This study aimed to evaluate the safety and performance of the TriGuard™ Embolic Deflection Device (EDD), a nitinol mesh filter positioned in the aortic arch across all three major cerebral artery take-offs to deflect emboli away from the cerebral circulation, in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: The prospective, multicentre DEFLECT I study (NCT01448421) enrolled 37 consecutive subjects undergoing TAVR with the TriGuard EDD. Subjects underwent clinical and cognitive follow-up to 30 days; cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) was performed pre-procedure and at 4±2 days post procedure. The device performed as intended with successful cerebral coverage in 80% (28/35) of cases. The primary safety endpoint (in-hospital EDD device- or EDD procedure-related cardiovascular mortality, major stroke disability, life-threatening bleeding, distal embolisation, major vascular complications, or need for acute cardiac surgery) occurred in 8.1% of subjects (VARC-defined two life-threatening bleeds and one vascular complication). The presence of new cerebral ischaemic lesions on post-procedure DW-MRI (n=28) was similar to historical controls (82% vs. 76%, p=NS). However, an exploratory analysis found that per-patient total lesion volume was 34% lower than reported historical data (0.2 vs. 0.3 cm3), and 89% lower in patients with complete (n=17) versus incomplete (n=10) cerebral vessel coverage (0.05 vs. 0.45 cm3, p=0.016). CONCLUSIONS: Use of the first-generation TriGuard EDD during TAVR is safe, and device performance was successful in 80% of cases during the highest embolic-risk portions of the TAVR procedure. The potential of the TriGuard EDD to reduce total cerebral ischaemic burden merits further randomised investigation.

Biolimus-eluting stents with biodegradable polymer versus bare-metal stents in acute myocardial infarction: two-year clinical results of the COMFORTABLE AMI trial.

BACKGROUND: This study sought to determine whether the 1-year differences in major adverse cardiac event between a stent eluting biolimus from a biodegradable polymer and bare-metal stents (BMSs) in the COMFORTABLE trial (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) were sustained during long-term follow-up. METHODS AND RESULTS: A total of 1161 patients were randomly assigned to biolimus-eluting stent (BES) and BMS at 11 centers, and follow-up rates at 2 years were 96.3%. A subgroup of 103 patients underwent angiography at 13 months. At 2 years, differences in the primary end point of cardiac death, target-vessel myocardial infarction, and target lesion revascularization continued to diverge in favor of BES-treated patients (5.8%) compared with BMS-treated patients (11.9%; hazard ratio = 0.48; 95% confidence interval, 0.31-0.72; P < 0.001) with a significant risk reduction during the second year of follow-up (hazard ratio 1-2 years = 0.45; 95% confidence interval, 0.20-1.00; P = 0.049). Differences in the primary end point were driven by a reduction in target lesion revascularization (3.1% versus 8.2%; P < 0.001) and target-vessel reinfarction (1.3% versus 3.4%; P = 0.023). The composite of death, any reinfarction and revascularization (14.5% versus 19.3%; P = 0.03), and cardiac death or target-vessel myocardial infarction (4.2% versus 7.2%; P = 0.036) were less frequent among BES-treated patients compared with BMS-treated patients. The 13-month angiographic in-stent percent diameter stenosis amounted to 12.0 ± 7.2 in BES- and 39.6 ± 25.2 in BMS-treated lesions (P < 0.001). CONCLUSIONS: Among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, BES continued to improve cardiovascular events compared with BMS beyond 1 year. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NTC00962416.

First-in-man evaluation of the MOMO cobalt-chromium carbon-coated stent.

AIMS: Bare metal stents continue to be used for the interventional treatment of coronary artery disease. We report the clinical and angiographic results of a multicentre, single-arm evaluation of safety and feasibility of the MOMO stent (Japan Stent Technology Co., Ltd, Okayama Research Park Incubation Centre, Okayama, Japan). METHODS AND RESULTS: The MOMO stent is a novel thin-strut cobalt-chromium carbon-coated stent for the treatment of de novo coronary artery disease (CAD). In this prospective, non-randomised, single-arm study, 40 patients (stable and unstable angina) with single-vessel CAD were recruited into the study from three centres. Patients with lesions ≤15 mm in length and with a target vessel diameter of ≥3 mm were eligible. Angiographic follow-up was performed at six months. Quantitative coronary angiography (QCA) was used to measure acute gain and late luminal loss (LLL). Intravascular ultrasound (IVUS) was performed in 15 consecutive patients from two centres to assess the degree of neointimal proliferation within the stented segment at six-month follow-up. The MOMO stent performed well without any procedural complications with an acute procedure and technical success rate of 100%. Repeat revascularisation was performed in six patients (15%) during the six-month follow-up. Ischaemia-driven revascularisation was documented in three patients (7.5%). No myocardial infarction, stent thrombosis or cardiac death was observed. One non-cardiac death was reported secondary to lung cancer. Binary restenosis was 12.5% (n=5), and the LLL was 0.54±0.3 mm. CONCLUSIONS: This first-in-man experience demonstrates proof of concept of the safety and feasibility of the MOMO cobalt-chromium carbon-coated stent for patients with single focal de novo lesions presenting with stable and unstable CAD.

Comparison of biolimus eluted from an erodible stent coating with bare metal stents in acute ST-elevation myocardial infarction (COMFORTABLE AMI trial): rationale and design.

AIMS: Compared with bare metal stents (BMS), early generation drug-eluting stents (DES) reduce the risk of revascularisation in patients with ST-elevation myocardial infarction (STEMI) at the expense of an increased risk of very late stent thrombosis (ST). Durable polymer coatings for controlled drug release have been identified as a potential trigger for these late adverse events and this has led to the development of newer generation DES with durable and biodegradable polymer surface coatings with improved biocompatibility. In a recent all-comers trial, biolimus-eluting stents with a biodegradable polymer surface coating were found to reduce the risk of very late ST by 80% compared with sirolimus-eluting stents with durable polymer, which also translated into a lower risk of cardiac death and myocardial infarction (MI) beyond one year. METHODS AND RESULTS: The multicentre COMFORTABLE AMI trial (NCT00962416) randomly assigned 1,161 patients to treatment with biolimus-eluting stents with biodegrable polymer and bare metal stents of otherwise identical design at 11 international sites. The primary endpoint is a composite of cardiac death, target-vessel MI and target lesion revascularisation at one year. Assuming a relative risk reduction of 40% in event rates of the primary endpoint in favour of biolimus-eluting stents with biodegradable polymer, 1,064 patients will provide 80% power to demonstrate superiority. Clinical follow-up will be continued through five years. CONCLUSIONS: The COMFORTABLE AMI trial will determine whether biolimus-eluting stents with biodegradable polymer are superior to bare metal stents of otherwise identical design. This is the first randomised controlled trial (RCT) investigating DES with a biodegradable polymer surface coating for drug release in the treatment of patients with STEMI.