Durable Polymer Zotarolimus-eluting Stent Research Articles

Biodegradable-Polymer or Durable-Polymer Stents in Patients at High Bleeding Risk: A Randomized, Open-Label Clinical Trial.

Limited information is available on the comparative efficacy and safety of different stent platforms in patients at high bleeding risk undergoing an abbreviated dual antiplatelet therapy duration after percutaneous coronary intervention (PCI). The aim of this study was to compare the safety and effectiveness of the biodegradable-polymer sirolimus-eluting stent with the durable-polymer zotarolimus-eluting stent in patients at high bleeding risk receiving 1 month of dual antiplatelet therapy after PCI. The Bioflow-DAPT Study is an international, randomized, open-label trial conducted at 52 interventional cardiology hospitals in 18 countries from February 24, 2020, through September 20, 2021. Patients with a clinical indication to PCI because of acute or chronic coronary syndrome who fulfilled 1 or more criteria for high bleeding risk were eligible for enrollment. Patients were randomized to receive either biodegradable-polymer sirolimus-eluting stents or durable-polymer, slow-release zotarolimus-eluting stents after successful lesion preparation, followed by 1 month of dual antiplatelet therapy and thereafter single antiplatelet therapy. The primary outcome was the composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year, and was powered for noninferiority, with an absolute margin of 4.1% at 1-sided 5% alpha. A total of 1948 patients at high bleeding risk were randomly assigned (1:1) to receive biodegradable-polymer sirolimus-eluting stents (969 patients) or durable-polymer zotarolimus-eluting stents (979 patients). At 1 year, the primary outcome was observed in 33 of 969 patients (3.6%) in the biodegradable-polymer sirolimus-eluting stent group and in 32 of 979 patients (3.4%) in the durable-polymer zotarolimus-eluting stent group (risk difference, 0.2 percentage points; upper boundary of the 1-sided 95% CI, 1.8; upper boundary of the 1-sided 97.5% CI, 2.1; P<0.0001 for noninferiority for both tests). Among patients at high risk for bleeding who received 1 month of dual antiplatelet therapy after PCI, the use of biodegradable-polymer sirolimus-eluting stents was noninferior to the use of durable-polymer zotarolimus-eluting stents with regard to the composite of death from cardiac causes, myocardial infarction, or stent thrombosis. URL: https://www. gov; Unique identifier: NCT04137510.

Outcome of percutaneous coronary intervention using ultrathin-strut biodegradable polymer sirolimus-eluting versus thin-strut durable polymer zotarolimus-eluting stents in patients with comorbid peripheral arterial disease: a post-hoc analysis from two randomized trials.

In patients with peripheral arterial disease (PADs), who underwent percutaneous coronary intervention (PCI), little is known about the potential impact of using different new-generation drug-eluting stents (DES) on outcome. In PCI all-comers, the results of most between-stent comparisons-stratified by strut thickness-suggested some advantage of coronary stents with ultrathin-struts. The current post-hoc analysis aimed to assess outcomes of PCI with ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) vs. thin-strut durable polymer zotarolimus-eluting stents (DP-ZES) in patients with PADs. We pooled 3-year patient-level data from two large-scale randomized all-comer trials to compare Orsiro ultrathin-strut BP-SES vs. Resolute-type thin-strut DP-ZES in trial participants with concomitant PADs. BIO-RESORT (December 2012 to August 2015) and BIONYX (October 2015 to December 2016) included all-comer patients who were aged 18 years or older, capable of providing informed consent, and required a PCI. The trials had web-based randomization, with block sizes of 4 and 8, performed in a 1:1:1 or 1:1 fashion. Assessors, research staff, and patients were blinded to the type of stent used. We assessed the composite main clinical endpoint target vessel failure [TVF: cardiac death, target vessel related myocardial infarction (MI), or clinically indicated target vessel revascularization (TVR)], its components, and stent thrombosis. Of 4,830 trial participants, 360 had PADs: 177 (49.2%) were treated with BP-SES and 183 (50.8%) with DP-ZES. Baseline characteristics were similar. For BP-SES, the 3-year TVF rate was 11.0% and for DP-ZES 17.9% [hazard ratio (HR): 0.59, 95% CI: 0.33-1.04; P=0.07]. For BP-SES, the TVR rate was lower than for DP-ZES (4.1% vs. 11.0%; HR: 0.36, 95% CI: 0.15-0.86; P=0.016), but this did not translate into between-group differences in cardiac death or MI. In small vessels (<2.75 mm), the TVR rate was also lower in BP-SES (5.6% vs. 13.9%; HR: 0.32, 95% CI: 0.11-0.91; P=0.024). Definite-or-probable stent thrombosis rates were 1.2% and 2.3% (P=0.43). In PCI patients with PADs, the 3-year TVF incidence was numerically lower in the ultrathin-strut BP-SES vs. the thin-strut DP-ZES group. Furthermore, TVR risk was significantly lower in ultrathin-strut BP-SES, mainly driven by a lower TVR rate in small vessels. BIO-RESORT trial: clinicaltrials.gov (NCT01674803); BIONYX trial: clinicaltrials.gov (NCT02508714).

Stent expansion in calcified coronary chronic total occlusions: The impact of different stent platforms.

To evaluate the stent expansion of the durable-polymer Zotarolimus-eluting stent (dp-ZES), the durable-polymer Everolimus-eluting stent (dp-EES), and the bioabsorbable-polymer Sirolimus-eluting stent (bp-SES) in calcified coronary chronic total occlusions (CTO). The newer generation stents with ultrathin struts might raise concerns regarding reduced radial strength and higher stent recoil (SR) when implanted in calcified CTOs. Between January 2017 and June 2021 consecutive patients with CTO undergoing percutaneous coronary intervention with dp-ZES, dp-EES, or bp-SES were evaluated. The analysis was performed in calcific and in noncalcific CTOs. Quantitative coronary angiography analysis was used to assess diameter stenosis (DS), absolute and relative SR, absolute and relative focal SR, absolute and relative balloon deficit (BD), and absolute and relative focal BD. The primary endpoint was DS. A total of 213 CTOs were evaluated, 115 calcific CTOs (dp-ZES:25, dp-EES:29, bp-SES:61) and 98 non-calcific CTOs (dp-ZES:41, dp-EES:11, bp-SES:46).In calcific CTOs, residual DS was lower in dp-ZES than in dp-EES and bp-SES (-1.00% [-6.50-6.50] vs. 13.00% [7.0-19.00] vs. 15.00% [5.00-20.00]; p < 0.001). Dp-ZES was also an independent predictor of residual DS ≤ 10% (OR 11.34, 95% CI 2.6-49.43, p = 0.001). Absolute and relative focal SR and absolute and relative SR were similar between dp-ZES, dp-EES, and bp-SES (p = 0.913, p = 0.890, p = 0.518, p = 0.426, respectively). In noncalcified CTOs, the residual DS was similar in the three groups (p = 0.340). High relative focal SR was less frequent in dp-ZES than in dp-EES and in bp-SES (19.5% vs. 54.5% vs. 37.0%; p < 0.048). The three stent platforms demonstrated an overall low residual DS when implanted in CTOs. However, dp-ZES was associated with the lowest residual DS and identified as independent predictor of residual DS ≤ 10% in patients with calcific CTOs. Dp-ZES was associated with a lower incidence of high relative focal stent recoil, in noncalcific CTOs. Balloon deficit might be considerate as a surrogate for stent expansion in calcified CTOs.

One-year outcomes of polymer-free amphilimus-eluting stents versus durable polymer zotarolimus-eluting stents in patients with diabetes mellitus: a meta-analysis

BackgroundDiabetes mellitus (DM) and cardiovascular diseases often co-exist. Today, percutaneous coronary intervention (PCI) is the preferred revascularization procedure for majority of patients with coronary artery disease. Polymer-free amphilimus-eluting stents (AES) represent a novel elution technology in the current era of drug-eluting stents. In this analysis, we aimed to systematically compare the cardiovascular outcomes which are associated with polymer-free amphilimus-eluting stents (AES) versus the durable polymer zotarolimus-eluting stents (ZES) for the treatment of patients with DM.MethodsHttp://www.ClinicalTrials.gov, EMBASE, Web of Science, MEDLINE, Cochrane database and Google Scholar were searched for publications comparing polymer-free AES versus durable polymer ZES in patients with DM. Selective cardiovascular outcomes were assessed. Statistical analysis was carried out by the latest version of the RevMan software. Risk ratio (RR) with 95% confidence interval (CI) was used to represent the data analysis.ResultsFour studies with a total number of 1795 participants with DM whereby 912 patients were assigned to be revascularized by the polymer-free AES and 883 patients were assigned to be revascularized by the durable polymer ZES were included in this analysis. In patients with DM, at one year, polymer-free AES were associated with significantly lower risk of major adverse cardiac events (MACEs) (RR: 0.69, 95% CI: 0.54–0.88; P = 0.002) and target lesion failure (TLF) (RR: 0.66, 95% CI: 0.48–0.91; P = 0.01) compared to durable polymer ZES. However, there was no significant change in all-cause mortality (RR: 0.79, 95% CI: 0.51–1.22; P = 0.28), cardiac death and the other cardiovascular outcomes. Similar risk of total stent thrombosis (RR: 1.13, 95% CI: 0.60–2.13; P = 0.70), including definite stent thrombosis (RR: 1.12, 95% CI: 0.38–3.31; P = 0.84), probable stent thrombosis (RR: 0.87, 95% CI: 0.37–2.09; P = 0.76), possible stent thrombosis (RR: 1.19, 95% CI: 0.50–2.87; P = 0.69) and late stent thrombosis (RR: 1.00, 95% CI: 0.17–5.72; P = 1.00) as between polymer-free AES and durable polymer ZES in patients with DM.ConclusionsAt 1 year follow-up, polymer-free AES were associated with significantly lower MACEs and TLF compared to durable polymer ZES in these patients with DM, without any increase in mortality, stent thrombosis and other cardiovascular outcomes. However, this analysis is only based on a follow-up time period of one year, therefore, future research should focus on the long term follow-up time period.

Procedural Performance of Ultrathin, Biodegradable-Polymer-Coated Stents Versus Durable-Polymer-Coated Stents Based on Intracoronary Imaging

Thinner stent struts might lead to a higher risk of recoil and subsequently a smaller minimal stent area (MSA), which is known to be the strongest predictor of stent failure. We compared procedural performance between an ultrathin-strut biodegradable-polymer sirolimus-eluting stent (BP-SES) and a durable-polymer zotarolimus-eluting stent (DP-ZES) using intracoronary imaging.A consecutive cohort of patients underwent percutaneous coronary intervention (PCI) with either BP-SES or DP-ZES in a pseudorandomized fashion between July 2018 and October 2019. In the present subanalysis, we included cases in which post-PCI imaging with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was performed. The primary endpoint of the study was MSA. Secondary endpoints included percentage stent expansion and presence of residual edge disease, malapposition, tissue protrusion, submedial edge dissections, or edge hematoma.A total of 141 treated lesions (78 BP-SES and 63 DP-ZES) in 127 patients were analyzed. Median age was 69.3 years (interquartile range [IQR], 57.3-75.6) and 74.0% of patients were male. All baseline and procedural characteristics were comparable between both groups. Median MSA was 5.80 mm² (IQR, 4.40-7.24) for BP-SES and 6.35 mm² (IQR, 4.76-8.31) for DP-ZES (P=.15). No significant differences in stent expansion, residual edge disease and presence of malapposition, tissue protrusion, submedial edge dissections, or edge hematomas were found. Stent diameter and stent length were found to be independent predictors of MSA.No significant differences in MSA were found between lesions treated with BP-SES vs DP-ZES. BP-SES and DP-ZES were comparable in terms of procedural performance.

Safety and efficacy of ticagrelor monotherapy according to drug-eluting stent type: the TWILIGHT-STENT study.

In the TWILIGHT trial, ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) was shown to be a safe bleeding avoidance strategy in high-risk patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). The aim of this study was to evaluate the effects of ticagrelor monotherapy after three-month DAPT in patients undergoing PCI, according to DES type. In the current sub-analysis from TWILIGHT, patients were stratified into three groups based on DES type: durable polymer everolimus-eluting stents (DP-EES), durable polymer zotarolimus-eluting stents (DP-ZES), and biodegradable polymer DES (BP-DES). Bleeding and ischaemic outcomes were assessed at one year after randomisation. Out of 5,769 patients, 3,014 (52.2%) had DP-EES, 1,350 (23.4%) had DP-ZES and 1,405 (24.4%) had BP-DES. Compared with ticagrelor plus aspirin, ticagrelor monotherapy had significantly lower BARC type 2, 3 or 5 bleeding compared with DAPT; DP-EES (3.8% vs 6.7%; HR 0.56, 95% CI: 0.41-0.78), DP-ZES (4.6% vs 6.9%; HR 0.66, 95% CI: 0.42-1.04) and BP-DES (4.2% vs 7.9%; HR 0.52, 95% CI: 0.33-0.81; pinteraction=0.76). Ticagrelor monotherapy resulted in similar rates of death, MI, or stroke: DP-EES (4.2% vs 4.3%; HR 0.97; 95% CI: 0.68-1.37); DP-ZES (4.1% vs 3.1%; HR 1.32; 95% CI: 0.75-2.33); BP-DES (3.9% vs 4.2%; HR 0.92; 95% CI: 0.54-1.55; pinteraction=0.60). In both unadjusted and covariate-adjusted analyses, DES type was not associated with any differences in ischaemic or bleeding complications. As compared with ticagrelor plus aspirin, ticagrelor monotherapy after a short DAPT duration lowered bleeding complications without increasing the ischaemic risk, irrespective of DES type. We observed no significant differences among DES types.

Ten-year clinical outcomes of polymer-free versus durable polymer new-generation drug-eluting stent in patients with coronary artery disease with and without diabetes mellitus

BackgroundVery long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus.MethodsWe investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years.ResultsThis analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73–1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88–1.11; P = 0.88).ConclusionAt 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time.Trial registrationClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533Graphic abstractKaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).

Elastic stent recoil in coronary total occlusions: Comparison of durable-polymer zotarolimus eluting stent and ultrathin strut bioabsorbable-polymer sirolimus eluting stent.

ObjectivesTo compare stent recoil (SR) of the thin‐strut durable‐polymer Zotarolimus‐eluting stent (dp‐ZES) and the ultrathin‐strut bioabsorbable‐polymer Sirolimus‐eluting stent (bp‐SES) in chronic total occlusions (CTOs) and to investigate the predictors of high SR in CTOs.BackgroundNewer ultrathin drug eluting stent might be associated with lower radial force and higher elastic recoil due to the thinner strut design, possibly impacting on the rate of in‐stent restenosis and thrombosis.MethodsBetween January 2017 and November 2019, consecutive patients with CTOs undergoing percutaneous coronary intervention were evaluated. Only patients treated with dp‐ZES or bp‐SES were included and stratified accordingly. Quantitative coronary angiography analysis was used to assess absolute SR, relative SR, absolute focal SR, relative focal SR, high absolute, and high relative focal SR.ResultsA total of 128 lesions (67 treated with dp‐ZES and 61 with bp‐SES) in 123 patients were analyzed. Between bp‐SES and dp‐ZES no differences were found in absolute SR (p = .188), relative SR (p = .138), absolute focal SR (p = .069), and relative focal SR (p = .064). High absolute and high relative focal SR occurred more frequently in bp‐SES than in dp‐ZES (p = .004 and p = .015). Bp‐SES was a predictor of high absolute focal SR (Odds ratio [OR] 3.29, 95% confidence interval [CI] 1.50–7.22, p = .003]. High‐pressure postdilation and bp‐SES were predictors of high relative focal SR (OR 2.22, 95% CI 1.01–4.86, p = .047; OR 2.74, 95% CI 1.24–6.02, p = .012, respectively).ConclusionsBoth stents showed an overall low SR. However, ultra‐thin strut bp‐SES was a predictor of high absolute and high relative focal SR.

Comparison of two iterations of the zotarolimus-eluting stents: an analysis of all-comer patients from two consecutive randomised clinical trials

Abstract Background The newest iteration of the durable polymer zotarolimus-eluting stents (ZES) is designed with thin swaged shape composite-wire struts (inner platinum–iridium core and outer cobalt–chromium layer). It is of interest to compare the clinical performance of this novel device with its predecessor in all-comers. Purpose The purpose of the present study is to assess 2-year clinical outcome in all-comer patients who were treated with the novel ZES versus the previous iteration ZES. Methods We did a post-hoc analysis of clinical outcome data of 2374 patients who were treated with the novel or the previous generation ZES (only nominal stent diameters that were available for both devices) in two consecutive large-scale randomised all-comer trials. A total of 1201 trial participants were treated with the novel ZES, and 1173 were treated with the previous generation ZES. The main outcome parameter target vessel failure is a composite of safety (cardiac death, target vessel myocardial infarction) and efficacy (target vessel revascularisation). Clinical outcome data were analysed with Kaplan-Meier methods and hazard ratios were computed with Cox regression analysis. An additional analysis was done in a subgroup of patients who presented with chronic coronary syndromes. Results The mean age of the study population was 63.9±10.9 years, 611 (25.7%) were female and 1669 (70.3%) presented with acute coronary syndromes. Two-year follow-up was available in 2346 (98.8%) participants. After 2 years, there was no significant difference between stent-groups in the rates of target vessel failure (7.2% vs. 8.3%, HR 0.85, 95% CI 0.64–1.14, p-logrank = 0.28; Figure 1) or its individual components. Peri-procedural myocardial infarction occurred less often in patients treated with the novel ZES (0.7% vs. 2.1%, p-logrank &amp;lt;0.01), and definite-or-probable stent thrombosis rates were low in both ZES groups (0.3% vs. 0.8%, p-logrank = 0.15). In a subgroup of 705 patients with chronic coronary syndromes, the rate of target vessel myocardial infarction tended to be lower with novel ZES (1.8% vs. 4.2%, p-logrank = 0.05). Conclusions The novel ZES showed similar 2-year clinical outcomes as compared to its predecessor. Furthermore, there was a positive safety signal regarding the incidence of target vessel myocardial infarction and a particularly low stent thrombosis rates with the novel ZES. Figure 1. Target vessel failure at 2 years Funding Acknowledgement Type of funding source: Other. Main funding source(s): Thoraxcentrum Twente has received institutional research grants provided by Abbott Vascular, Biotronik, Boston Scientific and Medtronic. The present analysis received no funding.

Diabetic patients treated with novel thin composite-wire strut zotarolimus-eluting stents versus ultrathin strut sirolimus-eluting stents in the BIONYX trial: 2-year results of a prespecified analysis

Abstract Background/Introduction The novel thin composite-wire strut zotarolimus-eluting stent (ZES) is a drug-eluting stent that is frequently used for treating patients with obstructive coronary artery disease, but so far no clinical outcome data have been published in patients with diabetes. In all-comer patients, the BIONYX trial (NCT02508714) has established non-inferiority of the ZES versus the ultrathin strut biodegradable-polymer sirolimus-eluting stent (SES) regarding the primary composite endpoint of target vessel failure at 1 year follow-up. Purpose To assess in patients with diabetes, the 2-year safety and efficacy of the current generation thin composite-wire strut ZES, compared to the ultrathin strut SES. Methods In the international, multicentre BIONYX trial, randomisation was stratified for sex and the presence of diabetes mellitus. We performed a prespecified subgroup analysis of patients with diabetes. The main endpoint target vessel failure was a composite of safety and efficacy, consisting of cardiac death, target vessel-related myocardial infarction or clinically indicated target vessel revascularisation. Secondary endpoints, such as target lesion revascularisation and stent thrombosis were also assessed. Results A total of 510/2488 (20.5%) BIONYX trial participants had diabetes, and were therefore included in this analysis. Patients were on average 66.4±10.3 years old, and 28.6% were female. Most participants presented with acute coronary syndromes (65.1%), and 182/510 (35.7%) patients were insulin dependent. Two-year follow up was available in 500 of 510 (98.0%) patients. Target vessel failure occurred in 31/260 (12.2%) patients assigned to ZES versus 26/250 (10.7%) patients assigned to SES (HR 1.14, 95%-CI 0.68–1.92; P-logrank=0.63). Kaplan Meier curves of target vessel failure are displayed in Figure 1. There were no significant between-stent differences in the individual components of this endpoint. Target lesion revascularisation occurred in 15/260 (6.0%) patients treated with ZES versus 9/250 (3.7%) patients treated with SES (HR 1.61, 95%-CI 0.71–3.68; P-logrank=0.25). Definite stent thrombosis was an infrequent event and did not differ significantly between stent-arms (0.4% vs. 1.2%; HR 0.32, 95%-CI 0.03–3.06; P-logrank=0.30). Conclusion In patients with diabetes, the novel thin composite-wire strut durable polymer ZES was similarly safe and efficacious as compared to the ultrathin cobalt-chromium strut biodegradable-polymer SES at 2-year follow-up. Figure1. Target vessel failure at 2 years Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The BIONYX trial was equally funded by Biotronik and Medtronic.

10-Year Outcomes From a Randomized Trial of Polymer-Free Versus Durable Polymer Drug-Eluting Coronary Stents

BackgroundOutcome data after extended long-term follow-up of patients with coronary artery disease treated with drug-eluting stents (DES) in randomized clinical trials are scant. ObjectivesPerformance differences among devices may be expected to emerge over time depending on whether stenting is done with polymer-free or durable polymer DES. This study assessed the 10-year outcomes of patients enrolled in the ISAR-TEST-5 (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents) trial. MethodsA total of 3,002 patients were randomized to treatment with either polymer-free sirolimus- and probucol-eluting stents (n = 2,002) or durable polymer zotarolimus-eluting stents (n = 1,000). The primary endpoint was the composite of cardiac death, target vessel–related myocardial infarction, or target lesion revascularization (a device-oriented composite endpoint [DOCE]). Additional endpoints of interest were the patient-oriented composite endpoint (POCE), including all-cause death, any myocardial infarction, or any revascularization; individual components of the composite endpoints; and definite or probable stent thrombosis. ResultsThe median age of the patients at randomization was 67.8 years. At 10 years, 63.9% of patients were alive. The rates of DOCE and POCE were high in both groups with no difference in the incidence between polymer-free sirolimus- and probucol-eluting stents and durable polymer zotarolimus-eluting stents (DOCE: 43.8% vs. 43.0%, respectively; hazard ratio: 1.01; 95% confidence interval [CI]: 0.89 to 1.14; p = 0.90; POCE: 66.2% vs. 67.7%, respectively; hazard ratio: 0.94; 95% CI: 0.86 to 1.04; p = 0.22). The rates of the individual components of the composite endpoints were comparable in both groups. The incidence of definite/probable stent thrombosis over 10 years was low and comparable in both groups (1.6% vs. 1.9%; hazard ratio: 0.85; 95% CI: 0.46 to 1.54; p = 0.58). ConclusionsAt 10 years, there were no measurable differences in outcomes between patients treated with polymer-free versus durable polymer DES. The incidence of stent thrombosis was low and comparable in both groups. High overall adverse clinical event rates were observed during extended follow-up. (Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents [ISAR-TEST-5]; NCT00598533)

Device profile of the Resolute Onyx Zotarolimus eluting coronary stent system for the treatment of coronary artery disease: overview of its safety and efficacy

ABSTRACT Introduction: The increasing complexity of patients undergoing percutaneous coronary intervention (PCI) regarding both coronary anatomy and comorbidities requires dedicated devices. The Resolute Onyx (R-Onyx, Medtronic, CA, USA) stent is a novel durable polymer zotarolimus-eluting stent (ZES) promising better deliverability, increased radiopacity and lower thrombogenicity. Areas covered: In this review, we discuss device features, preclinical evidence, and clinical studies including patients treated with R-Onyx. The BIONYX and Onyx ONE studies were two major landmark trials demonstrating non-inferiority of R-Onyx as compared to other latest generation devices. We also elaborate on alternative innovations in drug-eluting stent (DES) technology and how R-Onyx fits into this field. Expert opinion: R-Onyx is designed to address the challenges of contemporary PCI, but evidence on its clinical performance is largely derived from studies on older generation devices from the ZES family. Nonetheless, all clinical studies on R-Onyx consistently show excellent outcomes, with particularly low rates of stent thrombosis, making it a promising candidate for short dual antiplatelet regimens. In addition, R-Onyx is available with a wide range of stent diameters allowing accurate sizing for both very small and very large coronary vessels.

P3589New generation stents for primary percutaneous coronary intervention in patients with acute myocardial infarction: evidence from an individual patient data network meta-analysis of randomized clinical

Abstract Background Drug-eluting stents have shown their superiority in primary percutaneous intervention in patients with ST-segment elevation myocardial infarction (STEMI). No specific stent type has fully proven its superiority over others. Purpose We sought to compare the safety and efficacy of coronary artery stents in STEMI patients undergoing primary PCI through comprehensive network meta-analysis (NMA). Methods We performed an individual patient data (IPD) NMA of dedicated randomized trials in STEMI patients treated with coronary stents. The primary endpoint of interest was the composite outcome of cardiac death, any myocardial infarction (MI) or target lesion revascularization (TLR). Secondary outcomes were the individual component of the primary endpoint and definite or probable stent thrombosis. Outcomes were analyzed at the longest available follow-up. The primary analysis was performed using a one-stage random-effects meta-analysis. Results IPD from 15 randomized trials in STEMI patients were obtained including a total of 10,979 patients. Six different stent types were studied including bare metal stents (BMS), durable-polymer paclitaxel-eluting stents (DP-PES), durable-polymer sirolimus-eluting stents (DP-SES), durable-polymer zotarolimus-eluting stents (DP-ZES), durable-polymer everolimus-eluting stents (DP-EES) and biodegradable-polymer biolimus-eluting stent (BP-BES). Mean patient age was 60.7±11.9 years; 22.7% were female and 16.1% were diabetic. Median symptom onset to balloon time was 210 min. At a median follow-up of 3 years (interquartile range 2–4.9 years), patients treated with second-generation (DP-EES and BP-BES) or first-generation DES (DP-PES, DP-SES and DP-ZES) had significantly lower risk of the primary endpoint than patients treated with BMS (BMS vs. second-generation DES; HR 0.69, 95% CI 0.57–0.82, BMS vs. first-generation DES; HR 0.70, 95% CI 0.61–0.80). The differences were driven by the significant reduction of TLR associated with first- and second-generation DES compared with BMS. A trend towards lower risk of MI with second-generation DES compared with BMS or first-generation DES was observed (BMS vs. second-generation DES; HR 0.79, 95% CI 0.58–1.06, first- vs. second-generation DES; HR 0.75, 95% CI 0.54–1.03). Second-generation DES was associated with a significantly lower risk of definite or probable stent thrombosis compared with BMS (HR 0.62, 95% 0.40–0.97) and first-generation DES (HR 0.55, 95% CI 0.34–0.91). DP-EES and BP-BES had a similar risk of the primary endpoint, individual components of the primary endpoint, and definite or probable stent thrombosis. Conclusions In this larger-scale IPD NMA in STEMI patients, second-generation DES were superior to BMS with respect to long-term efficacy and safety outcomes. Second-generation DES were associated with a significant reduction of stent thrombosis compared with BMS and first-generation DES. Similar long-term outcomes were observed between DP-EES and BP-BES. Acknowledgement/Funding This study was funded by Biosensors International

P3385Difference of vascular healing after percutaneous coronary intervention between 4 kinds of new generation drug-eluting stents: an optical coherence tomography analysis

Abstract Background New generation drug eluting stents (DES) have improved target vessel failure as compared with early generation DES and bare metal stent. Contemporary several new generation DES are different each other regarding strut thickness and drug and polymer type. A little is known about which stent induces a more favorable vascular healing at follow up. Purpose In this study, we compared the vascular healing at 8-month follow up by optical coherence tomography (OCT) between 4 different kinds of new generation DES. Methods We enrolled 112 consecutive patients (121 lesions) who underwent PCI using 4 kinds of new generation DES including biodegradable-polymer everolimus-eluting stents (BP-EES), biodegradable-polymer sirolimus-eluting stents (BP-SES), durable-polymer everolimus-eluting stents (DP-EES) and durable-polymer zotarolimus-eluting stents (DP-ZES) and who underwent 8-month follow up angiogram and OCT between July 2016 and April 2018. We compared the OCT parameters including percentage of covered struts, uncovered struts, well-apposed and uncovered struts, malapposed strut and mean neointimal hyperplasia (NIH) thickness between them. Results BP-EES consisted of 29 lesions, BP-SES consisted of 25 lesions, DP-EES consisted of 38 lesions and DP-ZES consisted of 29 lesions. A total of 734 frames with 5163 struts in BP-EES, 481 frames with 4214 struts in BP-SES, 783 frames with 6119 struts in DP-EES and 583 frames with 4708 struts in DP-ZES were analyzed. As shown in a table, mean NIH thickness was significantly higher in BP-EES and BP-SES. Thus, we compared the OCT parameters between durable-polymer (DP) group including DP-ZES and DP-EES and biodegradable-polymer (BP) group including BP-EES and BP-SES. The percentage of uncovered struts was significantly lower and mean NIH thickness was significantly higher in BP group than DP group. Results of OCT parameters BP-EES (n=29) BP-SES (n=25) DP-EES (n=38) DP-ZES (n=29) P value BP group (n=54) DP group (n=67) P value Covered struts (%) 89.5±13.6 92.4±8.6 85.5±17.5 85.0±17.7 0.29 90.9±11.6 85.3±17.4 0.08 Uncovered struts (%) 8.8±10.8 7.1±8.7 14.5±17.5 15.0±17.7 0.14 8.0±9.9 14.7±17.4 0.03 Well-apposed and uncovered struts (%) 7.9±9.9 5.9±7.7 11.7±13.1 12.3±14.0 0.15 7.0±8.9 11.9±13.4 0.04 Malapposed struts (%) 0.8±1.6 1.3±2.2 2.7±5.8 2.7±4.7 0.33 1.0±1.9 2.7±5.3 0.07 Mean NIH thickness (μm) 102±57 121±48 78±28 88±33 &lt;0.01 111±53 82±31 &lt;0.01 Conclusion The present OCT study demonstrated that delayed neointimal healing characterized by the presence of uncovered struts and lower mean NIH thickness was less common in BP group than DP gruop. Biodegradable-polymer may be more favorable than durable-polymer from the point of view of vascular healing.

Temporal course of vascular healing and neoatherosclerosis after implantation of durable- or biodegradable-polymer drug-eluting stents.

Delayed healing and endothelial dysfunction may occur with drug-eluting stents (DES), promoting accelerated infiltration of lipids in the neointima and development of neoatherosclerosis (NA). Pathology data suggest durable polymer (DP) of DES to play a major role in this process. Whether biodegradable polymer (BP) may address these issues is uncertain. We compared in vivo vessel healing and NA of current generation BP- or DP-DES using serial optical coherence tomography (OCT) assessments. Ninety patients with multivessel coronary artery disease were randomized 1:1 to BP everolimus-eluting stents (EES, Synergy) or DP zotarolimus-eluting stents (ZES, Resolute Integrity). Co-primary endpoints were the maximum length of uncovered struts at 3 months (powered for non-inferiority) and the percentage of patients presenting with frames of NA at 18 months (powered for superiority) as measured by OCT. The maximum length of uncovered struts at 3 months was 10 ± 8 mm in the BP-EES group and 11 ± 7 mm in the DP-ZES group (mean difference -1 mm; upper 97.5% confidence interval +2 mm; P = 0.05 for non-inferiority; P = 0.45 for superiority). The percentage of patients presenting with frames of NA at 18 months was low and similar between BP-EES and DP-ZES groups (11.6% vs. 15.9%; P = 0.56). There was no stent thrombosis in both groups at 24 months. BP-EES and DP-ZES showed a similar healing response at 3 months and a low incidence of NA at 18 months. Biocompatible polymers, regardless of whether they are durable or biodegradable, may favourably impact the long-term vascular response to current-generation DES.

First-in-man randomised comparison of the BuMA Supreme biodegradable polymer sirolimus-eluting stent versus a durable polymer zotarolimus-eluting coronary stent: the PIONEER trial.

A second iteration of a sirolimus-eluting stent (SES) that has a biodegradable PLGA polymer coating with an electrografting base layer on a thin-strut (80 µm) cobalt-chromium platform (BuMA Supreme; SINOMED, Tianjin, China) has been developed. This first-in-man trial aimed to assess the efficacy and safety of the novel device. This randomised, multicentre, single-blinded, non-inferiority trial compared the BuMA Supreme SES versus a contemporary durable polymer zotarolimus-eluting stent (ZES) in terms of angiographic in-stent late lumen loss (LLL) at nine-month follow-up as the primary endpoint. A total of 170 patients were randomly allocated to treatment with either SES (n=83) or ZES (n=87). At nine-month angiographic follow-up, in-stent LLL was 0.29±0.33 mm in the SES group and 0.14±0.37 mm in the ZES group (pnon-inferiority=0.45). The in-stent percent diameter stenosis and the binary restenosis rate of the two treatment arms were similar (19.2±12.0% vs. 16.1±12.6%, p=0.09, and 3.3% vs. 4.4%, p=1.00, respectively). At 12-month clinical follow-up, there was no difference between treatment arms with regard to the device-oriented composite clinical endpoint (4.9% vs. 5.7%; p=0.72). The PIONEER trial did not meet its primary endpoint in terms of in-stent LLL at nine-month follow-up. However, this result did not translate into any increase in restenosis rate or impairment in 12-month clinical outcomes.

Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: 3-Year Clinical Outcomes in the Randomized SORT OUT VI Trial

ObjectivesThe authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. BackgroundBiodegradable-polymer biolimus-eluting stents are superior to first-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. MethodsThe study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target lesion revascularization); the individual endpoints of MACE; all-cause mortality; any myocardial infarction; target vessel revascularization; and definite or probable stent thrombosis at 36 months. ResultsFrom March 2011 to August 2012, 2,999 patients were randomly assigned (1:1) to receive either the zotarolimus-eluting (1,502 patients) or the biolimus-eluting (1,497 patients) stent. At 3-year follow-up, MACE occurred in 128 (8.6%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 144 (9.6%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.36). Occurrence of cardiac death (2.7% vs. 3.4%), myocardial infarction not clearly attributable to a non-target lesion (2.7% vs. 2.5%), and target lesion revascularization (5.4% vs. 5.5%) did not differ significantly between the 2 groups. Definite very late stent thrombosis occurred in 6 (0.4%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 10 (0.7%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.33). ConclusionsAt 3-year follow-up, the durable-polymer zotarolimus-eluting stent and the biodegradable-polymer biolimus-eluting stent were similar in clinical outcome, with no significant difference in safety and efficacy outcomes, including stent thrombosis.

Nobori-Biolimus-Eluting Stents versus Resolute Zotarolimus-Eluting Stents in Patients Undergoing Coronary Intervention: A Propensity Score Matching.

PurposeTo compare the 1-year outcomes of a durable polymer Zotarolimus-eluting stent (ZES) versus a biodegradable polymer Biolimus-eluting stent (BES) in patients undergoing percutaneous coronary intervention.Materials and MethodsA total of 2083 patients from 2 different registries, 1125 treated with BES in NOBORI registry and 858 received ZES in CONSTANT registry were included in this study. Clinical outcomes were compared with the use of propensity score matching (PSM). The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCEs) including cardiac death, myocardial infarction, clinically driven target lesion revascularization and stroke. Secondary end points were individual components of MACCEs as well as the incidence of stent thrombosis at 1-year follow-up.ResultsAfter PSM, 699 matched pairs of patients (n=1398) showed no significant difference between BES and ZES in the risk of composite MACCEs at 1 year (2.6% vs. 1.7%; p=0.36). Cardiac death was not statistically different between groups (0.7% vs. 0.4%, p=0.73). Target lesion revascularization rate was also similar between BES and ZES (1.1% vs. 0.7%, p=0.579). Non-Q wave myocardial infarction, as well as target-vessel revascularization rate, was similar between the two groups (0.14% for BES and 0.72% for ZES). Both stent types were excellent with no cases of stent thrombosis and rate of Q wave myocardial infarction reported during the follow-up period.ConclusionIn this cohort of patients treated with BES or ZES, the rate of MACCEs at 1 year was low and significantly not different between both groups.

Very thin strut biodegradable polymer everolimus-eluting and sirolimus-eluting stents versus durable polymer zotarolimus-eluting stents in allcomers with coronary artery disease (BIO-RESORT): a three-arm, randomised, non-inferiority trial

In patients with coronary artery disease, treated with durable polymer-coated drug-eluting stents, the life-long presence of the polymer might delay arterial healing. Novel very thin strut biodegradable polymer stents, which leave only a bare metal stent after polymer resorption, might improve long-term outcome. We investigated in allcomers the safety and efficacy of three stents eluting either everolimus, sirolimus, or zotarolimus, often clinically used but never compared, of which the biodegradable polymer everolimus-eluting stent was never before assessed in allcomers. The large-scale, investigator-initiated, multicentre, assessor and patient blinded, three-arm, randomised, BIO-RESORT non-inferiority trial was done at four clinical sites in the Netherlands. All-comer patients were aged 18 years or older, capable of providing informed consent, and required a percutaneous coronary intervention with drug-eluting stent implantation according to clinical guidelines or the operators' judgment. Exclusion criteria were: participation in another randomised drug or device study before reaching the primary endpoint of that study; planned surgery necessitating interruption of dual antiplatelet therapy within the first 6 months; known intolerance to components of the investigational product or medication required; uncertainty about the adherence to follow-up procedures or an assumed life expectancy of less than 1 year; or known pregnancy. Web-based computer-generated allocation sequences randomly assigned patients (1:1:1) to treatment with very thin strut biodegradable polymer everolimus-eluting or sirolimus-eluting stents (which differ substantially in type, amount, distribution, and resorption speed of their respective coating), or thin strut durable polymer zotarolimus-eluting stents. The primary endpoint was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (target vessel revascularisation) at 12 months of follow up with a very thin strut biodegradable polymer of either everolimus-eluting or sirolimus-eluting stents, compared with durable polymer zotarolimus-eluting stents, analysed by intention to treat (non-inferiority margin 3·5%). This trial was registered with ClinicalTrials.gov, number NCT01674803. From Dec 21, 2012, to Aug 24, 2015, 3514 patients were enrolled and analysed, of whom 2449 (70%) had acute coronary syndromes, which included 1073 (31%) ST-elevation myocardial infarctions. 12 month follow-up of 3490 (99%) patients (three lost to follow-up; 21 withdrawals) was available. The primary endpoint was met by 55 (5%) of 1172 patients assigned to everolimus-eluting stents, 55 (5%) of 1169 assigned to sirolimus-eluting stents and 63 (5%) of 1173 assigned to zotarolimus-eluting stents. Non-inferiority of the everolimus-eluting stents and sirolimus-eluting stents compared with zotarolimus-eluting stents was confirmed (both -0·7% absolute risk difference, 95% CI -2·4 to 1·1; upper limit of one sided 95% CI 0·8%, pnon-inferiority<0·0001). Definite stent thrombosis (defined by the Academic Research Consortium) occurred in four (0·3%) of 1172 patients who were allocated to everolimus-eluting stents, four (0·3%) of 1169 patients who were allocated to sirolimus-eluting stents, and three (0·3%) of 1173 patients who were allocated to zotarolimus-eluting stents (log-rank p=0·70 for both comparisons with zotarolimus-eluting stents). At 12 month follow-up, both very thin strut drug-eluting stents with dissimilar biodegradable polymer coatings (eluting either everolimus or sirolimus) were non-inferior to the durable polymer stent (eluting zotarolimus) in treating allcomers with a high proportion of patients with acute coronary syndromes. The absence of a loss of 1 year safety and efficacy with the use of these two biodegradable polymer-coated stents is a prerequisite before assessing their potential longer-term benefits. Biotronik, Boston Scientific, and Medtronic.

TCT-483 Angiographic and two-year clinical outcomes following percutaneous coronary intervention for in-stent restenosis of polymer-free sirolimus- and probucol-eluting stent compared with durable polymer zotarolimus-eluting stent

TCT-483 Angiographic and two-year clinical outcomes following percutaneous coronary intervention for in-stent restenosis of polymer-free sirolimus- and probucol-eluting stent compared with durable polymer zotarolimus-eluting stent