Endpoint Of Target Lesion Failure Research Articles

Comparison of Ridaforolimus-Eluting and Zotarolimus-Eluting Coronary Stents: 5-Year Outcomes From the BIONICS and NIREUS Trials.

The BIONICS (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis) and the NIREUS (BioNIR Ridaforolimus Eluting Coronary Stent System [BioNIR] European Angiography Study) randomized clinical trials showed noninferiority of the ridaforolimus-eluting stent (RES) compared with the zotarolimus-eluting stent (ZES) with respect to 1-year target-lesion failure and 6-month angiographic late lumen loss. We aimed to evaluate clinical outcomes between treatment groups over a 5-year follow-up. Patient-level data from the BIONICS (n=1919) and NIREUS (n=302) were pooled, comparing the outcomes of patients implanted with RES and ZES. The primary end point was the 5-year rate of target-lesion failure. A total of 2221 patients (63.2±10.3 years, 79.7% men) undergoing percutaneous coronary intervention with RES (n=1159) or ZES (n=1062) were included. Most clinical and angiographic characteristics were similar between groups. At 5 years, the primary end point of target-lesion failure was similar between treatment groups (12.2% RES versus 11.3% ZES, P=0.52). Rates of TLR (7.6% RES versus 6.8% ZES, P=0.42) target-vessel-related myocardial infarction (4.8% RES versus 4.9% ZES, P=0.95) and stent thrombosis (0.9% RES versus 0.9% ZES, P=0.87) also did not differ between groups. Target-vessel revascularization and cardiac death were higher among the RES group (12.3% versus 9.5% P=0.037, and 3.6% versus 2.2% P=0.042, respectively). However, after correction for baseline characteristics, there was no significant difference in cardiac death between groups. In a pooled analysis of 2 randomized trials, 5-year clinical outcomes were similar between patients undergoing percutaneous coronary intervention with RES and ZES. These results support the long-term safety and efficacy of RES for the treatment of patients with coronary artery disease.

Bioadaptor implant versus contemporary drug-eluting stent in percutaneous coronary interventions in Sweden (INFINITY-SWEDEHEART): a single-blind, non-inferiority, registry-based, randomised controlled trial

Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population. INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4·2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing. Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69·5 years (IQR 61·2-75·6), 575 (24·0%) of 2399 patients were female, and 1824 (76·0%) were male (data on race and ethnicity were not collected), and 1838 (76·6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2·4%) of 1189 assessable patients in the bioadaptor group versus 33 (2·8%) of 1192 assessable patients in the DES group, with a risk difference of -0·41% (95% CI -1·94 to 1·11; pnon-inferiority<0·0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0·3% (with events in three of 1170 patients) in the bioadaptor group versus 1·7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0·19 [95% CI 0·06 to 0·65]; p=0·0079), of target vessel failure were 0·8% (events in eight of 1167) versus 2·5% (events in 23 of 1174; 0·35 [0·16 to 0·79]; p=0·011), and of target lesion failure in patients with acute coronary syndrome were 0·3% (events in two of 906) versus 1·8% (events in 12 of 895; 0·17 [0·04 to 0·74]; p=0·018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0·7%] of 1201 in the bioadaptor group vs six [0·5%] of 1198 in the DES group; difference in event rates of 0·16% [95% CI -0·50 to 0·83]). Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing device-related events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings. Elixir Medical.

Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial

Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain. BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310. Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988). In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation. Biotronik.

Ten-year clinical outcomes from a randomized trial comparing new-generation everolimus-eluting stent versus first-generation Sirolimus-eluting stent: Results from the RESET extended study.

New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). During 10-yearof follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.

Three-year clinical outcomes of the novel sirolimus-eluting bioresorbable scaffold for the treatment of de novo coronary artery disease: A prospective patient-level pooled analysis of NeoVas trials.

We aimed to evaluate the long-term outcomes of the novel NeoVas sirolimus-eluting bioresorbable scaffold (BRS) for the treatment of de novo coronary artery disease. The long-term safety and efficacy of the novel NeoVas BRS are still needed to be elucidated. A total of 1103 patients with de novo native coronary lesions for coronary stenting were enrolled. The primary endpoint of target lesion failure (TLF) was defined as a composite of cardiac death (CD), target vessel myocardial infarction (TV-MI), or ischemia-driven-target lesion revascularization (ID-TLR). A three-year clinical follow-up period was available for 1,091 (98.9%) patients. The cumulative TLF rate was 7.2% with 0.8% for CD, 2.6% for TV-MI, and 5.1% for ID-TLR. Additionally, 128 (11.8%) patient-oriented composite endpoint and 11 definite/probable stent thromboses (1.0%) were recorded. The extended outcomes of the NeoVas objective performance criterion trial demonstrated a promising 3-year efficacy and safety of the NeoVas BRS in low-risk patients with low complexity in terms of lesions and comorbidities.

The standard versus prolonged dual antiplatelet therapy after the XINSORB bioresorbable scaffold implantation (SPARTA) trial: study protocol for a randomized controlled trial

BackgroundDual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after coronary stenting, including coronary stenting involving bioresorbable scaffolds (BRSs). Current clinical guidelines recommend at least 12 months of DAPT after BRS implantation. However, the correlation between prolonged DAPT and net clinical benefits remains unknown.MethodsThe SPARTA trial is designed to be a prospective, randomized, parallel-group, clinical trial. It aims to compare the benefits and risks of DAPT applied for either 12 or 36 months after XINSORB BRS implantation. The primary endpoints are the incidence of the composite endpoint of major adverse cardiac events (MACEs), including all-cause death, any myocardial infarction (MI), and all revascularizations, as well as Bleeding Academic Research Consortium Definition (BARC) type 3 or 5 bleeding events. The secondary endpoints of the study include the device-oriented composite endpoint of target lesion failure (defined as cardiac death, target vessel-related MI, or ischemia-driven target lesion revascularization), target vessel failure (defined as cardiac death, MI, or ischemia-driven target vessel revascularization), scaffold thrombosis, and minor bleeding events. This trial will enroll 2106 subjects treated with the XINSORB BRS only. All subjects will receive DAPT after the index procedure for 12 (± 1) months. Subjects without MACEs or major bleeding will be randomized to receive either 24 additional months of DAPT or aspirin alone.DiscussionThis trial is designed to investigate the impact of extending the duration of DAPT up to 3 years after XINSORB BRS implantation by investigating the balance of risks and benefits in a broad population of treated patients.Trial registrationClinicalTrials.gov NCT04501900. Registered on 6 August 2020.

Predictive value of cardiac troponin increase after percutaneous coronary intervention: is it just a marker of disease complexity?

Abstract Background/Introduction Peri-procedural myocardial infarction (MI) following percutaneous coronary intervention (PCI) is supposed to have an impact on outcome after PCI for stable coronary disease, but the rate of this event is highly dependent on their definitions. Most of the recently proposed definitions are based on cardiac troponin (hs-cTn) rise. Purpose The purpose of this analysis is to explore the impact of hs-cTn increase on mortality and cardiac events after PCI for chronic coronary disease with baseline normal value of hs-cTn. Methods e-ULTIMASTER is a large, all-comers registry that enrolled 37,198 patients worldwide who underwent PCI with a thin strut, cobalt chromium sirolimus-eluting stent. Risk-based monitoring was performed and all primary endpoint related events were adjudicated. Clinical follow-up was performed at 3 months and 1 year, with primary endpoint of target lesion failure (TLF) at 1 year. For this analysis, we selected patients with stable angina, silent ischemia, or unstable angina with normal hs-cTn values at baseline. We defined the cut-off value of hs-cTn level as the following: &amp;lt;10, 10–35, ≥35 upper limit of normal (ULN). To adjust for differences in baseline characteristics, a propensity analysis (inverse probability of treatment weights, IPTW) was done. Picture 1 shows variables included in the propensity score and differences between the groups (cTn&amp;lt;10 vs cTn 10–35 and cTn&amp;lt;10 vs cTn≥35) before and after matching. Results The number of patients in each subgroup is: hs-cTn&amp;lt;10 (n=3178), 10–35 (n=492), ≥35 (n=303). The mean age of each subgroup is respectively: 66.2; 68.1, 66.6 years (p&amp;lt;0.01). Across the three hs-cTn level groups, many baseline patient characteristics were similar but several lesion and procedure characteristics were significantly different across the three groups including bifurcation lesions, calcification, N of lesions treated, N of stents implanted, total stent length and procedural complications. The unadjusted and adjusted rates of 1-year clinical outcomes are presented in picture 2. All-cause or cardiac death were not increased in cTn≥35 group while there was a trend towards higher target lesion revascularization (TLR) and significantly higher stent thrombosis, majority of which (75% and 91% respectively) occurred during index hospitalization. There was a significantly higher rate of spontaneous MI in both groups with elevated hs-cTn. Conclusion Hs-cTn rise above 35 x ULN was not associated with cardiac or all-cause 1-year mortality. Significantly higher stent thrombosis and a trend towards higher TLR, observed in this group at 1-year, reflect procedure complications, based on the timing of event. When excluding peri-procedural MI in the matched analysis of outcomes, a significantly higher rate of spontaneous MI was observed in both groups with hs-cTn increase. The findings of this analysis suggest that hs-cTn rise is a marker of patient/lesion complexity. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Terumo Picture 1. Baseline variables before/after matchingPicture 2. 1-year clinical outcomes

Outcomes of 10,312 patients treated with everolimus-eluting bioresorbable scaffolds during daily clinical practice - results from the European Absorb Consortium.

To asses mid-term clinical outcomes of bioresorbable vascular scaffolds (BVS) for the treatment of coronary artery disease in a large-scale all-comers population. Several clinical settings are underrepresented in randomized studies investigating BVS against drug-eluting stents. Whether their results can be translated into the heterogeny patient population seen during daily routine requires further investigation. The European ABSORB Consortium comprises the following European registries: GABI-R, ABSORB UK Registry, ABSORB France, BVS RAI Registry, and REPARA BVS Registry, which all prospectively collected patient-level data regarding outcomes following unrestricted BVS implantation. The primary endpoint of target lesion failure (TLF) includes cardiac death, target-vessel myocardial infarction (TVMI) and target-lesion revascularisation (TLR) at 12 months. The incidence of scaffold thrombosis (ST) according to ARC criteria was also assessed. Multivariable analysis was used to adjust for differences in patient and lesion characteristics. A total of 10,312 patients (mean age 58.4 ± 11.4 y) underwent BVS implantation during routine practice. The 12-month follow-up was complete in 95.5% of patients. At 12 months, the primary endpoint of TLF occurred in 3.6%; its components cardiac death, TVMI and TLR were documented in 1.2%, 1.8%, and 2.6%, respectively. The definite/probable ST rate was 1.7%. Absence of predilatation, discontinuation of DAPT and scaffold diameter below 3 mm were independent predictors of ST. The EAC demonstrates reasonable real-world clinical outcome data after BVS implantation. However, the rate of scaffold thrombosis remains high.

Randomized Clinical Comparison of the Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Combo Stent With the Sirolimus-Eluting Orsiro Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT X Trial.

Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; P=0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; P=0.0012). The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733.

Ridaforolimus eluting stent for the treatment of Japanese patients with coronary disease: 1year outcomes of the JNIR study.

Japanese patients have shown improved outcomes after treatment with drug eluting stents compared with Western patients. Outcomes with the ridaforolimus-eluting EluNIR stent in Japanese patients are unknown. This was a multi-center trial in Japanese patients undergoing PCI with the ridaforolimus eluting EluNIR stent. A propensity-score matched analysis was performed with the EluNIR arm of the BIONICS trial. The matched cohort was compared with the Japanese patients for the primary endpoint of target lesion failure (TLF) in a non-inferiority study. 104 Japanese patients were compared with 410 matched patients from BIONICS. Baseline characteristics were similar except for more frequent multi-vessel disease in the BIONICS cohort. Post dilation was more likely in Japanese patients (90.4% vs. 64.6%, p < 0.001). TLF at 12months was met by 2 patients (1.9%) in the JNIR study compared with 5.3% in the BIONICS group (Pnoninf = 0.0028). Rates of MI (0% vs. 4.7%, p = 0.03), target vessel MI (0% vs. 3.7%, p = 0.04), MACE (1.0% vs. 6.2%, p = 0.03) and TVF (1.0% vs. 6.9%, p = 0.02) were all significantly lower among Japanese patients. Treatment of Japanese patients with the EluNIR stent is associated with very low rates of adverse events, significantly fewer than seen in the BIONICS trial.

Coronary Calcification and Long-Term Outcomes According to Drug-Eluting Stent Generation

ObjectivesThe aim of this study was to evaluate the long-term impact of coronary artery calcification (CAC) on outcomes after percutaneous coronary intervention and the respective performance of first- and second-generation drug-eluting stents (DES). BackgroundWhether contemporary DES have improved the long-term prognosis after percutaneous coronary intervention in lesions with severe CAC is unknown. MethodsIndividual patient data were pooled from 18 randomized trials evaluating DES, categorized according to the presence of angiography core laboratory–confirmed moderate or severe CAC. Major endpoints were the patient-oriented composite endpoint (death, myocardial infarction [MI], or any revascularization) and the device-oriented composite endpoint of target lesion failure (cardiac death, target vessel MI, or ischemia-driven target lesion revascularization). Multivariate Cox proportional regression with study as a random effect was used to assess 5-year outcomes. ResultsA total of 19,833 patients were included. Moderate or severe CAC was present in 1 or more target lesions in 6,211 patients (31.3%) and was associated with increased 5-year risk for the patient-oriented composite endpoint (adjusted hazard ratio [adjHR]: 1.12; 95% confidence interval [CI]: 1.05 to 1.20) and target lesion failure (adjHR: 1.21; 95% CI: 1.09 to 1.34), as well as death, MI, and ischemia-driven target lesion revascularization. In patients with CAC, use of second-generation DES compared with first-generation DES was associated with reductions in the 5-year risk for the patient-oriented composite endpoint (adjHR: 0.88; 95% CI: 0.78 to 1.00) and target lesion failure (adjHR: 0.73; 95% CI: 0.61 to 0.87), as well as death or MI, ischemia-driven target lesion revascularization, and stent thrombosis. The relative treatment effects of second-generation compared with first-generation DES were consistent in patients with and without moderate or severe CAC, although outcomes were consistently better with contemporary devices. ConclusionsIn this large-scale study, percutaneous coronary intervention of target lesion moderate or severe CAC was associated with adverse patient-oriented and device-oriented adverse outcomes at 5 years. These detrimental effects were mitigated with second-generation DES.

Clinical outcomes three-year after revascularization with biodegradable polymer stents: ultrathin-strut sirolimus-eluting stent versus biolimus-eluting stent: from the Scandinavian organization for randomized trials with clinical outcome VII trial.

Drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy. However, drug-eluting stents with biodegradable polymers may not be a class effect, as stent strut thickness, polymer coating, and drug resorption differ between these groups of stents. Twelve months results of Scandinavian Organization for Randomized Trials With Clinical Outcome VII showed that ultrathin-strut sirolimus-eluting Orsiro stent was noninferior to the biolimus-eluting Nobori stent. The sirolimus-eluting Orsiro stent was associated with a reduced risk of definite stent thrombosis. The Scandinavian Organization for Randomized Trials With Clinical Outcome VII trial is a prospective multicenter randomized clinical trial comparing sirolimus-eluting Orsiro stent and biolimus-eluting Nobori stent in all-comers patients. The endpoint target lesion failure was a composite of cardiac death, myocardial infarction (not related to other than index lesion) and target lesion revascularization. A total of 1261 patients were randomized to treatment with sirolimus-eluting Orsiro stent and 1264 patients to biolimus-eluting Nobori stent and followed for 3 years. At 3-year the target lesion failure was comparable for sirolimus-eluting Orsiro stent (9.0%) and the biolimus-eluting Nobori stent (9.1%), (rate ratio, 0.99; 95% confidence interval, 0.77-1.29). Cardiac death (sirolimus-eluting Orsiro stent 3.0% vs. biolimus-eluting Nobori stent 2.6% [rate ratio, 1.16; 95% confidence interval, 0.73-1.86]), target lesion revascularization (sirolimus-eluting Orsiro stent 5.2% vs. biolimus-eluting Nobori stent 5.9% [rate ratio, 0.90; 95% confidence interval, 0.64-1.25]), myocardial infarction (sirolimus-eluting Orsiro stent 4.7% vs. biolimus-eluting Nobori stent 4.5% [rate ratio, 1.04; 95% confidence interval, 0.72-1.50]), and definite stent thrombosis (sirolimus-eluting Orsiro stent 1.0% vs. biolimus-eluting Nobori stent 1.7% [rate ratio, 0.59; 95% confidence interval, 0.30-1.18]) did not differ significantly between the two groups. At 3-year follow-up, target lesion failure did not differ among ultrathin-strut sirolimus-eluting Orsiro stent and biolimus-eluting Nobori stent with biodegradable polymers.

P1966Impact of coronary artery calcification on long-term outcomes after implantation of first and second-generation drug-eluting stents: a patient-level analysis of 18 randomized trials

Abstract Background Available data on the long-term impact of coronary artery calcification (CAC) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) are limited. Purpose We evaluated the long-term impact of CAC on outcomes after PCI and the respective performance of first- and second-generation DES. Methods We pooled patient-level data from 18 randomized trials evaluating DES categorized according to the presence of angiographic core lab-confirmed moderate or severe CAC in any target lesion. Outcome measures of interest were the patient-oriented composite endpoint (POCE; death, myocardial infarction [MI], or any revascularization), the device-oriented composite endpoint of target lesion failure (TLF; cardiac death, target vessel MI or ischemia-driven target lesion revascularization), and definite or probable stent thrombosis (ST). Multivariable Cox proportional regression with study as a random effect was used to assess 5-year outcomes. Results A total of 19,833 patients were included. Moderate or severe CAC was present in 6211 (31.3%) patients and associated with increased 5-year risk of the POCE (adjHR 1.12, 95% CI 1.05–1.20, p&lt;0.001), TLF (adjHR 1.21, 95% CI 1.09–1.35, p&lt;0.001), and a trend for greater ST (adjHR 1.24, 95% CI 0.99–1.54, p=0.06). In patients with CAC, second-generation DES were associated with a reduction in the 5-year risk of TLF and ST, and a trend for reduced POCE compared with first-generation DES (Table). Conclusion In this large-scale study, target lesion moderate or severe CAC was associated with adverse patient- and device-related outcomes at 5 years, risks that were reduced but not eliminated with second-generation DES. Acknowledgement/Funding This investigator-sponsored study was funded by Abbott Vascular.

Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI): a single-blind, prospective, randomised superiority trial

Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. The BIOSTEMI trial was an investigator-initiated, multicentre, prospective, single-blind, randomised superiority trial at ten hospitals in Switzerland. Patients aged 18 years or older with acute STEMI who were referred for primary PCI were eligible to participate. Patients were randomly allocated (1:1) to either biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Central randomisation was done based on a computer-generated allocation sequence with variable block sizes of 2, 4, and 6, which was stratified by centre, diabetes status, and presence or absence of multivessel coronary artery disease, and concealed using a secure web-based system. Patients and treating physicians were aware of group allocations, whereas outcome assessors were masked to the allocated stent. The experimental stent (Orsiro; Biotronik; Bülach, Switzerland) consisted of an ultrathin strut cobalt-chromium metallic stent platform releasing sirolimus from a biodegradable polymer. The control stent (Xience Xpedition/Alpine; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut cobalt-chromium stent platform that releases everolimus from a durable polymer. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial reinfarction (Q-wave and non-Q-wave), and clinically-indicated target lesion revascularisation, within 12 months of the index procedure. All analyses were done with the individual participant as the unit of analysis and according to the intention-to-treat principle. The trial was registered with ClinicalTrials.gov, number NCT02579031. Between April 26, 2016, and March 9, 2018, we randomly assigned 1300 patients (1623 lesions) with acute myocardial infarction to treatment with biodegradable polymer sirolimus-eluting stents (649 patients and 816 lesions) or durable polymer everolimus-eluting stents (651 patients and 806 lesions). At 12 months, follow-up data were available for 614 (95%) patients treated with biodegradable polymer sirolimus-eluting stents and 626 (96%) patients treated with durable polymer everolimus-eluting stents. The primary composite endpoint of target lesion failure occurred in 25 (4%) of 649 patients treated with biodegradable polymer sirolimus-eluting stents and 36 (6%) of 651 patients treated with durable polymer everolimus-eluting stents (difference -1·6 percentage points; rate ratio 0·59, 95% Bayesian credibility interval 0·37-0·94; posterior probability of superiority 0·986). Cardiac death, target vessel myocardial reinfarction, clinically-indicated target lesion revascularisation, and definite stent thrombosis were similar between the two treatment groups in the 12 months of follow-up. In patients with acute STEMI undergoing primary PCI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 1 year. This difference was driven by reduced ischaemia-driven target lesion revascularisation in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents. Biotronik.

A prospective multicentre randomised all-comers trial to assess the safety and effectiveness of the thin-strut sirolimus-eluting coronary stent SUPRAFLEX: rationale and design of the Thin Strut Sirolimus-eluting Stent in All Comers Population vs Everolimus-eluting Stent (TALENT) trial.

The aim of this study is to compare the SUPRAFLEX sirolimus-eluting stent (SES) with the XIENCE everolimus-eluting stent (EES) with respect to target lesion failure (TLF) at 12 months in a non-inferiority trial in a "real-world" patient population. This is a prospective, randomised, 1:1 balanced, controlled, single-blind, multicentre study comparing clinical outcomes at 12 months between SUPRAFLEX and XIENCE in an "all-comers" patient population, comprising a total of 1,430 enrolled subjects with symptomatic coronary artery disease who qualify for percutaneous coronary interventions at 23 centres in Europe. The primary endpoint is a non-inferiority comparison of the device-oriented composite endpoint target lesion failure (cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularisation) of the SUPRAFLEX group to the XIENCE group at 12 months post procedure. Secondary endpoints include the patient-oriented composite endpoint, target vessel failure, mortality, myocardial infarction, revascularisation and stent thrombosis rates (ARC classification). The TALENT trial aims to assess the safety and effectiveness of the thin-strut SUPRAFLEX compared to the current standard of care (XIENCE EES) in patients with atherosclerotic lesions. This will provide valuable information on the impact of this thin-strut device in an all-comers population.

7-Year Outcomes of a Randomized Trial Comparing the First-Generation Sirolimus-Eluting Stent Versus the New-Generation Everolimus-Eluting Stent: The RESET Trial

ObjectivesThe aim of this study was to compare 7-year outcomes between the first-generation sirolimus-eluting stent (SES) and the new-generation everolimus-eluting stent (EES) in a randomized clinical trial. BackgroundThere is a scarcity of very long-term (beyond 5 years) data from clinical trials investigating whether new-generation drug-eluting stents have clear clinical advantages over first-generation drug-eluting stents. MethodsRESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) is the largest randomized trial comparing EES with SES (NCT01035450). Among a total of 3,197 patients in the original RESET population from 100 centers, the present extended 7-year follow-up study was conducted in 2,667 patients from 75 centers after excluding those patients enrolled from centers that denied participation. Complete 7-year follow-up was achieved in 91.5% of patients. ResultsThe cumulative 7-year incidence of the primary efficacy endpoint of target lesion revascularization was not significantly different between EES and SES (10.2% vs. 11.7%; hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.10; p = 0.24). The risk for the primary safety endpoint of death or myocardial infarction trended lower with EES than with SES (20.6% vs. 23.6%; hazard ratio: 0.85; 95% confidence interval: 0.72 to 1.005; p = 0.06). The cumulative 7-year incidence of definite stent thrombosis was very low and similar between EES and SES (0.9% vs. 1.0%; p = 0.82). The lower risk of EES relative to SES was significant for the composite secondary endpoint of target lesion failure (13.3% vs. 18.1%; hazard ratio: 0.72; 95% confidence interval: 0.59 to 0.88; p = 0.001). ConclusionsDuring 7 years of follow-up, the risk for target lesion revascularization was not significantly different between the new-generation EES and the first-generation SES.

Comparison of the polymer-free biolimus-coated BioFreedom stent with the thin-strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population treated with percutaneous coronary intervention: Rationale and design of the randomized SORT OUT IX trial

In patients with increased bleeding risk during dual antiplatelet therapy, the biolimus A9-coated BioFreedom, a stainless steel drug-coated stent devoid of polymer, has shown superiority compared to a bare-metal stent. The aim of this study was to investigate whether the polymer-free biolimus A9-coated BioFreedom is noninferior to a modern thin-strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. The multicenter SORT OUT IX trial (NCT02623140) randomly assigned all-comers patients to treatment with the BioFreedom drug-coated stent or the biodegradable polymer Orsiro stent in 4 Danish University Hospitals. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection based on Danish registries will be used and continue through 5 years. Assuming an event rate of 4.2% in each stent group, 1,563 patients in each treatment arm will provide 90% power to detect noninferiority of the drug-coated BioFreedom stent with a noninferiority margin of 2.1%. A total of 3,150 patients have been randomized and enrolled in the study. The SORT OUT IX trial will determine whether the drug-coated BioFreedom stent is noninferior to a modern biodegradable polymer Orsiro stent.

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable polymer coronary stent (TARGET All Comers): a multicentre, open-label, randomised non-inferiority trial

The FIREHAWK is a drug-eluting stent with a fully biodegradable sirolimus-containing polymer coating localised to recessed abluminal grooves on the stent surface. We investigated clinical outcomes with this targeted, low-dose, biodegradable polymer, sirolimus-eluting stent compared with XIENCE durable polymer, everolimus-eluting stents in an all-comers population. The TARGET All Comers study was a prospective, multicentre, open-label randomised non-inferiority trial done at 21 centres in ten European countries. Patients with symptomatic or asymptomatic coronary artery disease and objective evidence of myocardial ischaemia who qualified for percutaneous coronary intervention were randomised 1:1 to undergo implantation of a FIREHAWK or XIENCE. Randomisation was web-based, with random block allocation and stratification by centre and ST elevation myocardial infarction. Outcome assessors were masked to treatment allocation, but treating physicians and patients were not. The primary endpoint was target lesion failure at 12 months, a composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation. The control event rate for XIENCE was assumed to be 7%, the non-inferiority margin was 3.5%, and the primary analysis was in the intention-to-treat population, censoring patients who did not have either an event before 365 days or contact beyond 365 days. Late lumen loss was the primary endpoint of an angiographic substudy designed to investigate the non-inferiority of the FIREHAWK compared with the XIENCE stent. This trial is registered with ClinicalTrials.gov, number NCT02520180. From Dec 17, 2015, to Oct 14, 2016, 1653 patients were randomly assigned to implantation of the FIREHAWK (n=823) or XIENCE (n=830). 65 patients in the FIREHAWK group and 66 in the XIENCE group had insufficient follow-up data and were excluded from the analyses. At 12 months, target lesion failure occurred in 46 (6·1%) of 758 patients in the FIREHAWK group and in 45 (5·9%) of 764 patients in the XIENCE group (difference 0·2%, 90% CI -1·9 to 2·2, pnon-inferiority=0·004, 95% CI -2·2 to 2·6, psuperiority=0·88). There were no differences in ischaemia-driven revascularisation or stent thrombosis rates at 12 months. 176 patients were included in the angiographic substudy, in which in-stent late lumen loss was 0·17 mm (SD 0·48) in the FIREHAWK group and 0·11 mm (0·52) in the XIENCE group (p=0·48), with an absolute difference of 0·05 mm (95% CI -0·09 to 0·18, pnon-inferiority=0·024). In a broad all-comers population of patients requiring stent implantation for myocardial ischaemia, the FIREHAWK was non-inferior to the XIENCE as assessed with the primary endpoint of target lesion failure at 12 months and in-stent late lumen loss at 13 months. The FIREHAWK is a safe and effective alternative stent to treat patients with ischaemic coronary artery disease in clinical practice. Shanghai Microport Medical.

Non-Inferiority of Resolute Integrity Drug-Eluting Stent to Benchmark Xience Drug-Eluting Stent

The Resolute Integrity coronary drug-eluting stent (DES), the next evolution of the Resolute DES, is designed with thinner stent struts and continuous sinusoidal technology to further enhance performance. This study evaluated the performance of the Resolute Integrity DES compared with the historical performance of Xience V. Methods and Results: We assessed the safety, efficacy, and deliverability of Resolute Integrity compared with the Xience DES, the prespecified historical control, in PROPEL, a large, real-world prospective, single-arm, open-label study. A total of 1,204 subjects were enrolled in PROPEL and treated with the Resolute Integrity DES at 76 sites in Japan. Lesion and procedural success rates were 100% and 99%, respectively. Patients were equally complex in the Resolute Integrity and Xience cohorts. At 1 year in the clinical-only cohort, the primary endpoint target lesion failure was 4.3% (34/800) in the Resolute Integrity cohort compared with 8.5% (97/1,142) in the Xience historical controls (P<0.001 for non-inferiority). Target vessel failure, major adverse cardiac events, target vessel myocardial infarction, and the composite cardiac death and target vessel myocardial infarction were all lower with Resolute Integrity compared with Xience, including in "high risk" patients. In the large, prospective, multicenter PROPEL trial, the performance of the Resolute Integrity DES was non-inferior to that of the benchmark Xience DES used as a historical comparator.

Randomized clinical comparison of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent with the sirolimus-eluting Orsiro stent in patients treated with percutaneous coronary intervention: Rationale and study design of the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X trial

BackgroundThe Combo stent (OrbusNeich, Hoevelaken, the Netherlands) combining an abluminal, bioabsorbable polymer eluting sirolimus with a luminal CD34+ antibody to capture endothelial progenitor cells has been developed to further improve safety and efficacy of coronary interventions. We have designed a large-scale registry-based randomized clinical trial to compare the Combo stent to the Orsiro stent (Biotronik, Bülach, Switzerland) in patients undergoing percutaneous coronary intervention. MethodsThe SORT OUT X study will randomly assign 3,140 patients to treatment with Combo or Orsiro stents at 3 sites in Western Denmark. Patients are eligible if they are ≥18 years old, have chronic stable coronary artery disease or acute coronary syndromes, and have ≥1 coronary lesion with >50% diameter stenosis requiring treatment with a drug-eluting stent. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection will be derived from validated Danish registries. An event rate of 4.2% is assumed in each stent group. With a sample size of 1,570 patients in each treatment arm, a 2-group large-sample normal approximation test of proportions with a 1-sided 5% significance level will have 90% power to detect noninferiority of the Combo stent compared with the Orsiro stent with a predetermined noninferiority margin of 2.1%. ConclusionThe SORT OUT X trial will determine whether the dual-therapy Combo stent is noninferior to the Orsiro stent with respect to clinically driven events (ClinicalTrials.govNCT03216733).