LEADERS FREE Research Articles

Clinical outcomes with thin versus thick strut polymer-free biolimus-coated stents at 3 years

BackgroundFor high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the safety and efficacy of a stainless steel...

Safety and efficacy of the latest generation biodegradable polymer-coated ultrathin sirolimus-eluting stent in the treatment of coronary artery disease in a European all-comer population with or without high bleeding risk: The Cruz HBR Registry.

The latest generation ultrathin Supraflex Cruz (Sahajanand Medical Technologies Limited, Surat, India) sirolimus-eluting stent (SES) has shown early healing properties and represents an attractive percutaneous coronary intervention (PCI) device in a high bleeding risk (HBR) population. The aim of this Cruz HBR registry was to assess safety and efficacy of the Supraflex Cruz SES in a large cohort of all-comer patients, of whom about one third were patients at HBR. Patients undergoing PCI were enrolled in this prospective, multi-centre, open label registry and stratified into non-HBR and HBR groups. The primary endpoint was a device-oriented composite endpoint (DOCE), a composite of cardiovascular death, myocardial infarction not clearly attributable to a non-target vessel and clinically driven target lesion revascularization within 12 months after PCI. The predefined aims were to show non-inferiority of the non-HBR group to the Supraflex arm of the TALENT Trial, and of the HBR group to polymer-free biolimus-coated stent arm of LEADERS FREE Trial. A total of 1203 patients were enrolled across 26 European centers, including a significant proportion (38.7%; N.=466) of HBR patients. A total of 1745 lesions were treated in 1203 patients and 2235 stents were implanted. The DOCE occurred within the total cohort in 5.8% of patients with a significant difference between HBR patients and non-HBR patients (8.1% vs. 4.4%; P<0.001). All-cause mortality at 12 months was significantly (P<0.0001) different among HBR (9.0%) and non-HBR patients (1.7%), respectively. At 12 months, the overall incidence of definite and probable stent thrombosis was 1.0%. Major bleeding occurred in 5.9% patients of the HBR group. These results met the non-inferiority criteria with respect to the TALENT trial for the non-HBR group (P<0.0001), and the LEADERS FREE trial for the HBR group (P<0.0001). The Cruz HBR registry confirms that PCI with the Supraflex Cruz SES is associated with a favorable clinical outcome in an all-comer population, including complex patients with HBR.

Safety and efficacy of drug-eluting stents for patients at high risk of bleedings: A network meta-analysis.

Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided. A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones. A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95%CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best. In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis.

One-month dual antiplatelet therapy following stent implantation in patients with acute coronary syndromes and high bleeding risk

Abstract Background/introduction There is a paucity of data regarding the safety of a one-month dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) presenting with acute coronary syndromes (ACS). Purpose We aimed to compare the clinical outcomes of patients at HBR with ACS or chronic coronary syndromes (CCS) treated with PCI using bioresorbable-polymer everolimus-eluting stent followed by one-month DAPT. Methods This is a pre-specified sub-analysis of the POEM trial, an interventional, prospective, multicenter, single-arm trial, that evaluated the safety of PCI with bioresorbable-polymer everolimus-eluting stent followed by one-month DAPT in patients with HBR against an objective performance criterion (OPC). The OPC was derived from the reported 1-year primary endpoint rate of 9.4% observed in the LEADERS FREE trial. According to the POEM protocol, patients were treated with one-month DAPT. In case of need for anticoagulation, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for one month, followed by oral anticoagulation only after that. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. Results 263 (59.4%) patients with CCS and 180 (40.6%) patients with ACS were included. Most of the HBR inclusion criteria were comparable between the two groups, Figure 1. At one year, the rates of the primary outcome were 4.3% (95% CI, 2.4-7.6%) and 5.7% (95% CI, 3.1-10.3%) among patients with CCS and ACS, respectively. Both 1-sided 97.5% upper confidence limits of the risk difference between the primary outcome and the prespecified OPC of 9.4% were below the non-inferiority margin of 3.85 % (CCS: -1.8 %; ACS: 0.9 %), Figure 2. No significant difference was evident between CCS and ACS patients for each isolated component of the primary endpoint (cardiac death: 1.7% vs. 2.0%, p= 0.857; myocardial infarction: 3.9% vs. 3.1%, p= 0.934; definite/probable stent thrombosis: 1.2% vs. 0.8%, p= 0.689). The risk for Bleeding Academic Research Consortium (BARC) type 1-5 or type 3-5 bleedings was also similar between CCS and ACS patients (4.3% vs. 5.2%, p=0.677, and 1.6% vs. 2.9%, p=0.351, respectively). Conclusions Among HBR patients with ACS who underwent PCI with BP-EES, a one-month DAPT strategy is associated with a similar risk of ischemic and bleeding events compared to those with CCS. These findings support the hypothesis that DAPT should be tailored to patients’ bleeding risk profiles and that a one-month strategy might be safely applied also in a particular setting of ACS.Figure 1.HBR inclusion criteria.Figure 2.Primary endpoint analysis.

Abstract 17686: Safety and Efficacy of Drug-Eluting Stents for Patients at High Risk of Bleedings: A Network Meta-Analysis

Introduction: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided. Methods: A Network Meta Analysis was performed including all Randomized Controlled Trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones. Results: A total of 4 studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and DAPT length (1 or 6 months) on 12 months follow-up. About one third of these patients were defined HBR due to indication for oral anticoagulation. All Drug Eluting Stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95%CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best. Conclusion: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis

Biofreedom France registry: A prospective evaluation of clinical outcomes in real-world patients treated by coronary angioplasty with Biolimus A9 polymer-free Biofreedom stents

The Biolimus A9 polymer-free Biofreedom stent was shown to be superior to bare metal stents in terms of efficacy and safety in the randomized controlled clinical trial LEADERS FREE in high bleeding risk (HBR) patients treated by one-month DAPT. To assess prospectively the two-year clinical outcomes in a real-world population treated by coronary angioplasty with Biofreedom stents. 1502 patients (74% men, mean age 72 years) were enrolled in 26 French centers. 756 (50.33%) patients presented at least one criterion of HBR. Multi-lesion procedure was performed in 30% of patients with implantation of 1.56 stent/patient. Patients were followed by phone contact at 3, 12 and 24 months. The primary endpoint (device-oriented) was composed of cardiovascular death, myocardial infarction or clinically driven target lesion revascularization at 12 months. The secondary patient-oriented end point was a composite of all-cause death, any stroke, any myocardial infarction and any revascularization at 12 and 24 months. Further secondary endpoints were BARC 3 to 5 bleeding, or stent thrombosis. At 3-month and 12-month follow-up the primary composite end point was observed in 32 (2.14%) and 84 (6.2%) patients, respectively, including cardiovascular death in 17 (1.14%) and 24 (1.69%), myocardial infarction in 8 (0.54%) and 12 (0.85%), and clinical driven target lesion revascularization in 12 (0.85%) and 59 (4.51%) patients. Stent thrombosis occurred in 6 (0.4%) and 14 (1.02%) patients at three months and one year, and stroke was observed in 8 (0.54%) and in 13 (0.93%). Bleeding BARC 3 to 5 was observed in 17 (1.14%) and 32 (2.31%) at 3 and 12 months. Two-year follow up is currently ongoing. This prospective registry confirms the excellent safety and efficacy profile of the Biolimus A9 polymer-free Biofreedom stent in a real-world population of patients with ischemic heart disease treated by angioplasty.

Polymer-free Biolimus-A9 coated thin strut stents for patients at high bleeding risk 1-year results from the LEADERS FREE III study.

BackgroundIn patients at high bleeding risk (HBR), the LEADERS FREE (LF) trial established the safety and efficacy of a polymer‐free drug coated (Biolimus‐A9) stainless steel stent (SS‐DCS) with 30 days of dual antiplatelet treatment (DAPT). In LEADERS FREE III, we studied a new cobalt‐chromium thin‐strut stent (CoCr‐DCS) in HBR patients.MethodsThe CoCr‐DCS shares all of the design features of the SS‐DCS but has a CoCr stent platform with strut thickness of 84–88 μm. The primary safety endpoint was a composite of cardiac death, myocardial infarction (MI), and definite/probable stent thrombosis. The primary efficacy endpoint was clinically indicated target lesion revascularization. Outcomes were compared to those of LF (non‐inferiority to SS‐DCS for safety and superiority to SS‐BMS for efficacy). Additional propensity‐matched comparisons were performed to account for baseline differences.ResultsWe recruited 401 HBR patients using identical criteria to the LF trial. At 1 year, the primary safety endpoint was reached by 31/401 (8.0%) of patients treated with the CoCr‐DCS versus 35/401 (8.9%) for the propensity‐matched cohort (HR: 0.89, [0.55–1.44], p < 0.001 for non‐inferiority, 0.62 for superiority). The efficacy endpoint was reached by 16/401 (4.2%) of CoCr‐DCS patients versus 41/401 (10.6%) in the propensity‐matched cohort (HR: 0.4 [0.2:0.7]) (p = 0.007 for superiority). There was no statistical difference between CoCr‐DCS and SS‐DCS in terms of efficacy (HR: 1.46 [0.68–3.15], p = 0.33).ConclusionsThe new thin‐strut CoCr‐DCS proved non‐inferior to the SS‐DCS for safety, and superior to the BMS for efficacy in HBR patients treated with 30 days of DAPT.

Sex-based outcomes in contemporary antiplatelet therapy trials

Balancing ischaemic and bleeding risks in high-risk populations undergoing percutaneous coronary interventions has become an everyday dilemma for clinicians. It is particularly difficult to make decisions concerning combinations and duration...

The Biolimus A9-coated BioFreedom™ stent: from clinical efficacy to real-world evidence.

In this state-of-the-art review, we present the findings and a critical analysis of the Leaders Free trial program, evaluating outcomes of a new stent-generation based on polymer-free technology, in this case the BioFreedom™ (Biosensors Europe, Switzerland), in patients at high bleeding risk (HBR). Polymer-free drug-coated stents were designed to obtain a device with the antirestenotic benefits of drug-eluting stents but without the polymer coating as potential trigger for delayed arterial wall healing and subsequent late ischemic adverse events, causing a prolonged dependence on dual antiplatelet therapy after stenting. This offers therefore the potential of a promising device-based strategy in a complex growing population of patients with combined HBR and high thrombosis risk, due to the possible reduction of antithrombotic duration.

Drug-coated stents versus bare metal stents in Academic Research Consortium-defined high bleeding risk patients.

More effective and progressively safer generations of drug-elut-ing stents (DES) have replaced bare metal stents (BMS) in rou-tine clinical practice. However, patients considered to be at high bleeding risk (HBR) have traditionally been underrepresented in pivotal DES trials. The aim of this study was to model the safety and effectiveness of drug-coated stents (DCS) versus BMS in HBR patients according to the Academic Research Consortium (ARC) criteria. Participants from the LEADERS FREE (LF) and LEADERS FREE II (LFII) studies were pooled into one data set. Participants were treated with 30 days of DAPT. The primary safety (composite of cardiac death, myocardial infarction, or stent thrombosis) and effectiveness (target lesion revascularisation) endpoints were compared between DCS and BMS in the subgroup of patients satisfying the ARC-HBR definition using propensity-score modelling. From the 3,635 participants included in the combined LF and LFII data set, 2,898 (79.7%) satisfied the ARC-HBR criteria (DCS: 1,923; BMS: 975). The primary safety endpoint occurred in 184 (9.8%) and in 132 (13.8%) participants in the DCS and BMS groups, respectively (adjusted HR 0.72, 95% CI: 0.57-0.91; p=0.006). The risk of the primary effectiveness endpoint was also significantly lower with DCS (6.2%) versus BMS (8.8%) (adjusted HR 0.70, 95% CI: 0.52-0.94; p=0.016). The safety and effectiveness of DCS versus BMS were consistent according to ARC-HBR status (p for interaction=0.206 and 0.260, respectively). DCS are safer and more effective than BMS in an ARC-defined HBR population.

Polymer-free drug-coated vs. bare-metal coronary stents in patients undergoing non-cardiac surgery: a subgroup analysis of the LEADERS FREE trial.

To compare the outcomes of patients undergoing non-cardiac surgery (NCS) after PCI with either a drug-coated stent (DCS) or a bare-metal stent (BMS), followed by 1-month dual antiplatelet therapy and to explore the impact of the timing of NCS. This is a subgroup analysis of the LEADERS FREE trial. The primary safety end point was a composite of cardiac death, myocardial infarction, or stent thrombosis, and the primary efficacy end point was clinically driven target lesion revascularization (TLR). Out of 2432 patients included in the LEADERS FREE trial, 278 (11.4%) underwent NCS within 1 year after PCI. Among NCS patients, the 1-year safety end point was numerically lower with DCS; however, this difference was not significant as compared to BMS (4.7% vs. 10.1%, HR: 0.459 [0.178-1.183], p = 0.099), clinically driven TLR was significantly lower after DCS (2.4% vs. 8.3%, HR: 0.281 [0.079-0.996], p = 0.036), and BARC 3-5 bleeding was similarwith DCS vs. BMS (10.2% vs. 7.5%, p = 0.438). In patients treated with BMS, NCS within 3 months after PCI was associated with higher incidence of the safety end point than NCSs performed later: 14.9% vs. 4.4%, HR: 3.586 [1.012-12.709], p = 0.034. The timing of surgery had no impact on patients treated with DCS (4.7% vs. 4.7%, p = 0.947). Among patients undergoing NCS after PCI, DCS-treated patients had a lower probability of clinically driven TLR compared with BMS. However, there was no significant difference in the occurrence of the primary composite safety end point or bleeding complications. Early NCS after BMS-PCI was associated with impaired safety, while the timing of NCS had no such influence after DCS implantation.

Sex-Based Outcomes in Patients With a High Bleeding Risk After Percutaneous Coronary Intervention and 1-Month Dual Antiplatelet Therapy

Female sex has been identified as a risk factor for bleeding after percutaneous coronary intervention (PCI) and may have contributed to the underuse of drug-eluting stents in women. This risk may be further enhanced among patients with a high bleeding risk. To assess the 2-year outcomes by sex in patients with a high bleeding risk who were enrolled in the LEADERS FREE trial. This cohort study is a prespecified, sex-based secondary analysis of the LEADERS FREE double-blind, randomized clinical trial that was conducted at 68 sites in 20 countries from December 2012 to May 2014. Patients with a high bleeding risk who underwent PCI and met the trial eligibility criteria were enrolled at the participating sites and followed up for up to 2 years. Patients were randomized 1:1 to either a bare-metal stent or a polymer-free, biolimus A9-eluting drug-coated stent with 1-month of dual antiplatelet therapy. The primary safety end point was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target lesion revascularization. Bleeding was assessed using the Bleeding Academic Research Consortium (BARC) scale, and the source of bleeding was recorded. A total of 2432 patients with a high bleeding risk were included in the study. Of these patients, the mean (SD) age was 75 (9) years, and 1694 (69.7%) were men and 738 (30.3%) were women. Women and men had similar incidence of the 2-year primary safety (14.7% vs 13.6%; P = .37) and efficacy (9.2% vs 9.5%; P = .70) end points. The drug-coated stent was found to be superior to the bare-metal stent in both sexes, with lower target lesion revascularization (women: 6.3% vs 12.1%; men: 7.0% vs 12.0%; P for interaction = .70) and similar rates of the primary safety end point (women: 12.4% vs 17.0%; men: 12.6% vs 14.5%; P for interaction = .40). Overall, 2-year BARC types 3 to 5 major bleeding (10.2% vs 8.6%; P = .14) was not statistically different between the sexes, but women experienced greater BARC types 3 to 5 major bleeding within the first 30 days (5.1% vs 2.4%; P = .007) and greater vascular access site major bleeding than men (2.2% vs 0.5%; P < .001). In both sexes, vascular (women: hazard ratio [HR], 3.45 [95% CI, 1.51-7.87]; men: HR, 4.14 [95% CI, 1.33-12.95]) and nonvascular major bleeding (women: HR, 3.76 [95% CI, 2.17- 6.53]; men: HR, 4.62 [95% CI, 3.23-6.61]) were associated with greater 2-year mortality. This study found no sex differences in the ischemic outcomes of patients with a high bleeding risk after PCI, but women appeared to demonstrate greater early bleeding and major bleeding from the vascular access site. Both women and men with major bleeding seemed to experience worse 2-year mortality, suggesting that bleeding avoidance strategies should be uniformly adopted for all patients, with close attention dedicated to women to avoid denying them the benefits of PCI. ClinicalTrials.gov Identifier: NCT02843633.

Impacto del acceso vascular en el pronóstico tras la angioplastia coronaria en pacientes con alto riesgo hemorrágico: subanálisis predefinido del estudio LEADERS FREE

Introduction and objectivesThe prognostic impact of bleeding in high bleeding risk (HBR) patients depending on the location of bleeding and prognosis in nonaccess site bleeding is unknown. We aimed to assess the impact of vascular access site on bleeding complications after percutaneous coronary interventions for HBR patients at 30-day and 2-year follow-up. MethodsThe LEADERS FREE trial included 2432 HBR PCI patients. A Biolimus A9 drug-coated stent was superior to a bare-metal stent for safety and efficacy. This is a predefined sub-analysis of the LEADERS FREE trial. ResultsTransradial access (TRA) was used in 1454 patients (59.8%) and transfemoral access (TFA) in 978 (40.2%), according to operator preference. The safety and benefits of drug-coated stents over bare-metal stents were independent of vascular access. At 30 days and 2 years, major bleeding had occurred in 2.4% and 7.5% of TRA patients and 4.6% and 10.9% of TFA patients (P=.003), respectively. Most of these events in both groups (2.1% and 7.0% for TRA; 3.2% and 9.4% for TFA, respectively) were nonaccess site-related. TRA was associated with a significant reduction in adjusted rates of major bleeding both at 30 days (HR, 1.98; 95%CI, 1.25-3.11; P=.003) and at 2 years of follow-up (HR, 1.51; 95%CI, 1.14-2.01; P=.003). This difference was driven by both access and nonaccess bleeding. ConclusionsOperators preferred TRA for most HBR patients, which was associated with a significant reduction in major bleeding events. However, most of these events in this population are unrelated to vascular access.

MAPT (Mono Antiplatelet Therapy) as Regular Regimen After COBRA PzF™ NanoCoated Coronary Stent (NCS) Implantation

AimsTo report procedural and 1-year outcomes following COBRA PzF NCS implantation in a routine daily setting with high bleeding risk (HBR) patients treated with clopidogrel as mono antiplatelet therapy (MAPT). MethodsThis is a prospective, consecutive, observational study in HBR patients who underwent PCI with COBRA PzF NCS and treated with clopidogrel alone at discharge. The primary endpoint was definite stent thrombosis at one month. The secondary endpoint was MACE (Cardiac Death, myocardial infarction (MI), target lesion revascularization (TLR)) at 12 months. ResultsFrom October 2015 to December 2018, 77 patients with 120 lesions were enrolled and treated. Mean age was 78.7 ± 8.89 years, 58.5% men and 18.2% had ACS. Patients included had a minimum of 2.0 inclusion LEADERS FREE criteria. Angiographic success was achieved in all cases. The primary endpoint occurred in 0%, no stent thrombosis was occurred. MACE at 12-months (available for 52 patients) was 3.8% including cardiac death 0%, MI 0% and TLR 3.8%. No severe bleeding events (BARC3–5) or stroke or late stent thrombosis were noted. ConclusionClopidogrel as MAPT after COBRA PzF NCS implantation in HBR patients is feasible and an attractive option. One-year follow-up was associated with excellent clinical outcomes and should be confirmed with large randomised study. Condensed abstractThis is prospective registry of high bleeding risk patients treated with the COBRA PzF NCS and MAPT at discharge. The primary end point demonstrated no stent thrombosis. The rate of major cardiac adverse events (a composite of cardiovascular death, myocardial infarction and target lesion revascularisation) at 1 year was 3.8%. No severe bleeding events, stroke or late stent thrombosis were noted. One-year follow-up was associated with good clinical outcomes and compared favorably with current devices.

P2794Real-world reasons and outcomes for 1-month versus longer dual antiplatelet therapy strategies with a polymer-free biolimus A9-coated stent: insights from the all-comers FREEDOM registry

Abstract Background The LEADERS FREE trial established the favourable clinical profile of a new polymer-free biolimus A9-eluting stent (PF-BES) in patients at high bleeding risk when used with a 1-month dual anti-platelet therapy (DAPT) strategy. Purpose This is the first study evaluating real-world reasons and outcomes for a 1-month versus longer DAPT strategies following PF-BES percutaneous coronary intervention (PCI). Methods FREEDOM is an all-comers registry including all patients who underwent PCI with at least one PF-BES at 10 sites, between January 2016 and July 2018. Patients were stratified according to DAPT strategy at discharge (1-month vs &gt;1-month). Baseline features, reasons for PF-BES as reported by the treating physician, and outcomes were compared between groups. Primary outcomes were the 390-day estimates of a patient-oriented composite endpoint (POCE: death, myocardial infarction (MI) or target vessel revascularization) and of a device-oriented composite endpoint (DOCE: cardiac death, target vessel-MI or ischemia-driven target lesion revascularization). Incidence rates were adjusted for clinically relevant factors and outcome predictors. To avoid survival bias, landmark analyses starting from 1-month post-PCI were further carried. Results Following PF-BES PCI, 328 (40.3%) patients were discharged with 1-month DAPT and 485 (59.6%) patients with longer DAPT (median 12 months, IQR 6–12 months). Patients with hypertension or on oral anticoagulation (OAT) were more likely and patients with a previous or an index MI were less likely to be discharged on 1-month DAPT. Patients prescribed with 1-month DAPT were more likely to have had a PF-BES for a LEADERS FREE high bleeding risk criterium than those with longer DAPT (90.2% vs 69.9%, p=0.001). The same association was observed when the reason for PF-BES was a planned major surgery (13.1% vs 6.2%; p=0.001) or OAC to be continued after PCI (38.7% vs 16.5%, p&lt;0.001). Conversely, patients with planned longer DAPT were more likely to have had a PF-BES following the operator preference (2.4% vs 15.5%, p&lt;0.001) or for a reason other than a LEADERS FREE criterium or operator preference (5.2% vs 11.3%, p&lt;0.001). No between-groups differences in the occurrence of the primary outcomes (1-month vs &gt;1-month DAPT: POCE 11.9% vs 13.2%, p=0.747; adj-HR 1.29 [95% CI 0.78–2.10]; DOCE: 4.8% vs 8.1%, p=0.500; adj-HR 1.01 [95% CI 0.50–2.07]) and of bleedings (any: 11.3% vs 9.4%, p=0.472; adj-HR 0.87 [95% CI 0.51–1-50]; BARC 3–5: 4.2% vs 2.2%; p=0.108; adj-HR 1.50 [95% CI 0.58–3.87]) were observed. Landmark analyses showed similar results. Conclusions In a large contemporary all-comers registry, factors reflecting the operator-perceived patient high bleeding risk were the main drivers of a very-short DAPT strategy following PF-BES PCI. We found no interaction of DAPT duration with outcomes following PF-BES PCI, an observation warranting investigation in adequately powered randomised studies.

Impact of vascular access on outcome after PCI in patients at high bleeding risk: a pre-specified sub-analysis of the LEADERS FREE trial.

The prognostic impact of bleeding in high bleeding risk (HBR) patients depending on the location of bleeding and prognosis in nonaccess site bleeding is unknown. We aimed to assess the impact of vascular access site on bleeding complications after percutaneous coronary interventions for HBR patients at 30-day and 2-year follow-up. The LEADERS FREE trial included 2432 HBR PCI patients. A Biolimus A9 drug-coated stent was superior to a bare-metal stent for safety and efficacy. This is a predefined sub-analysis of the LEADERS FREE trial. Transradial access (TRA) was used in 1454 patients (59.8%) and transfemoral access (TFA) in 978 (40.2%), according to operator preference. The safety and benefits of drug-coated stents over bare-metal stents were independent of vascular access. At 30 days and 2 years, major bleeding had occurred in 2.4% and 7.5% of TRA patients and 4.6% and 10.9% of TFA patients (P=.003), respectively. Most of these events in both groups (2.1% and 7.0% for TRA; 3.2% and 9.4% for TFA, respectively) were nonaccess site-related. TRA was associated with a significant reduction in adjusted rates of major bleeding both at 30 days (HR, 1.98; 95%CI, 1.25-3.11; P=.003) and at 2 years of follow-up (HR, 1.51; 95%CI, 1.14-2.01; P=.003). This difference was driven by both access and nonaccess bleeding. Operators preferred TRA for most HBR patients, which was associated with a significant reduction in major bleeding events. However, most of these events in this population are unrelated to vascular access.

Determinants of Significant Out-Of-Hospital Bleeding in Patients Undergoing Percutaneous Coronary Intervention.

Although several variables have been identified as bleeding determinants (BDs), their occurrence and predictive value in patients undergoing percutaneous coronary intervention (PCI) in the real world remain unclear. We aimed to characterize the rate of BDs in patients undergoing PCI with stent implantation in a large volume tertiary centre. We included patients undergoing coronary stenting at our institution from January 2012 to December 2016, and defined post-discharge bleeding (PDB) as bleeding requiring hospitalization or transfusion. Several BDs, identified by the PARIS bleeding and PRECISE-DAPT scores and inclusion criteria of the LEADERS FREE trial, were analysed. In a population of 10,406 subjects who underwent PCI, 2,938 patients (28.2%) had 1, 2,367 (22.8%) had 2 and 2,913 (28.0%) had ≥3 pre-specified BD. Compared with patients without PDB, subjects who experienced PDB were older (70.43 ± 11.94 vs. 65.90 ± 11.54 years, p < 0.0001) with a higher prevalence of common cardiovascular risk factors. One-year PDB occurred in 177 patients (2.4%), and consistently increased according to the number of BDs involved (1.12, 2.11 and 4.35%, respectively; p < 0.0001). Analogously, 1-year rates of post-discharge myocardial infarction or stent thrombosis increased according to the number of BDs (2.44, 3.38 and 4.87%, respectively; p < 0.0001). Only 7 BDs remained independently associated with PDB at 1 year, with anaemia, oral anticoagulant at discharge and malignancy representing the strongest predictors of such risk. Many risk factors predispose to PDB; they were often clustered together and conferred additive PDB risk at 1-year of follow-up.

Biolimus A9 polymer-free coated stents in high bleeding risk patients undergoing complex PCI: evidence from the LEADERS FREE randomised clinical trial.

The LEADERS FREE trial has demonstrated that a polymer-free Biolimus A9-coated stent (BA9-DCS) is superior to a bare metal stent (BMS) for high bleeding risk (HBR) patients when treated with one month of dual antiplatelet therapy (DAPT). This analysis aimed to determine the impact of PCI procedure complexity on the two-year results. Six hundred and sixty-seven (667) patients enrolled in the LEADERS FREE (BA9-DCS 346, BMS 321) underwent a complex PCI, defined by one or more of eight characteristics: total stent length ≥60 mm, ≥3 vessels or lesions treated, ≥3 stents implanted, bifurcation lesion treated with ≥2 stents, chronically occluded, restenotic or saphenous vein graft lesion. Patients undergoing complex PCI were older, more often male, and presented with more ACS, diabetes, renal insufficiency, anaemia and multivessel disease. They derived major benefit from DCS over BMS for safety (16.2% vs. 21.7%, HR 0.70 [0.49-0.99], p<0.05) and for efficacy (10.8% vs. 18.1%, HR 0.54 [0.35-0.83], p<0.005). For the 1,746 patients with non-complex PCI, DCS demonstrated superior efficacy (5.3% vs. 9.9%, HR 0.52 [0.36-0.75], p<0.001, p for interaction NS) and similar safety to BMS (11.1% vs. 12.6%, NS, p for interaction NS). Compared to BMS, the BA9-DCS maintained both efficacy and safety benefits when used in complex PCI procedures.

Polymer-free drug-coated coronary stents in diabetic patients at high bleeding risk: a pre-specified sub-study of the LEADERS FREE trial.

Diabetics are at increased risk after stent implantation and potentially sensitive to the type of stent and dual anti-platelet therapy (DAPT). The randomized, double-blind LEADERS FREE trial compared 2432 patients at high bleeding risk (HBR) receiving either a polymer-free BA9-coated stent (DCS) or a bare metal stent (BMS) with 1 month of DAPT, and showed superior safety and efficacy of the DCS at 2 years. We report outcomes at 2 years of the pre-specified diabetic subgroup. The diabetic sub-group comprised 805 (33.1%) patients; 262 (10.8%) were insulin-dependent (IDDM). Compared to non-diabetics, diabetics were younger and had more risk factors and multi-vessel disease. They suffered higher rates of death (15.6 vs. 12.2%, p = 0.01), cardiac death (8.3 vs. 5.9%, p = 0.02), myocardial infarction (MI) (11.1 vs. 7.8%, p = 0.009) and definite/probable stent thrombosis (3.1 vs. 1.7%, p = 0.01), but rates of clinically-indicated TLR (9.1 vs. 9.5%, p = 0.93) and BARC 3-5 bleeding (10.2 vs. 8.4%, p = 0.20) were comparable. Compared to diabetic patients treated with a BMS, diabetic DCS recipients required less clinically driven TLR (6.3 vs. 12.2%, p = 0.006). The primary safety endpoint (cardiac death, MI, definite/probable stent thrombosis) occurred numerically less frequently in the DCS group (14.9 vs. 19.7%, p = 0.10), and was significantly lower in IDDM patients (13.8 vs. 25.4%, p = 0.03). BARC 3-5 was similar for patients treated with DCS (9.9%) and BMS (10.5%, p = 0.84). In diabetic HBR patients, DCS significantly reduced re-intervention rates over BMS, and showed a strong trend towards a safety benefit at 2years. ClinicalTrials.gov number: NCT01623180.

Polymer-free biolimus-A9-coated stent for primary percutaneous coronary intervention.

The polymer-free biolimus-A9 drug-coated stent (DCS) was reported to have superior safety and efficacy outcomes compared with abare metal stent in the LEADERS FREE trial of high-bleeding-risk patients with acute coronary syndrome and on dual antiplatelet treatment (DAPT) for 1month. The aim of this investigation was to evaluate the DCS in aconsecutive cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). We analyzed data from 164 consecutive STEMI patients who underwent PPCI using the DCS at our institution. The primary efficacy endpoint was clinically indicated target lesion revascularization (ciTLR); the primary safety endpoint was acomposite of cardiac death, myocardial infarction, and definite/probable stent thrombosis. Clinical outcomes at 1year are presented here. The mean age of the patients was 61.5 ± 15.5years, and 86.6% were male. The median symptom-to-balloon-time was 55 min. In 57.9% of patients (n = 95), the infarct had an anterior location. PPCI achieved Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 163 of 164 patients (99.4%). All patients were prescribed DAPT for 1year. At 1year, ciTLR occurred in 1.2% of patients, the primary safety endpoint was reached in 4.3% of patients, and definite stent thrombosis was noted in 0.6% of patients. In this consecutive real-world cohort of patients, the DCS was safe and efficacious when used for PPCI in patients with STEMI.