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Background: Transcatheter aortic valve implantation (TAVI) is preferred for treating severe aortic stenosis in older, frail populations, yet the impact of frailty on economic and clinical outcomes of TAVI is not well studied., Methods: This retrospective cohort study included 2175 TAVI patients from 2015 to 2019, using Korea's National Health Insurance Service database, stratifying patients into low, intermediate, and high-frailty groups, using the Hospital Frailty Risk Score (HFRS). Health care costs, admissions, and total length of hospitalization were analyzed using Wilcoxon-rank test 12 months pre- and post-TAVI. Composite endpoint of death, stroke, and major bleeding, with individual outcomes, were compared using χ 2 tests and Kaplan-Meier analysis., Results: Mean age was 80.2 years, and 47.3% were male; 747 (34.3%) were low frailty, 1159 (53.3%) were moderate frailty, and 269 (12.4%) were high frailty. After TAVI, medical costs decreased in the intermediate- (pre-TAVI: 2,269,000 KRW [$1668 USD], post-TAVI: 1,607,000 KRW [$1181 USD]; P < 0.001) and high-frailty groups (pre-TAVI: 3,949,000 KRW [$2904 USD], post-TAVI: 2,188,000 KRW [$1609 USD]; P < 0.001). All frailty groups had shorter length of hospital stay post-TAVI (26 to 21 days in the low-frailty, 44 to 31 days in the intermediate-frailty, and 65 to 41 days in the high-frailty group; all P <0.001). The composite outcome was higher in the frailer groups (27.8% in the low-frailty vs 31.5% in the intermediate-frailty vs 37.9% in the high-frailty group; P = 0.008). All groups showed comparable rates of cardiovascular death, stroke, or bleeding., Conclusions: TAVI is clinically viable and cost-saving treatment option for frail patients with severe aortic stenosis., (Copyright © 2024. Published by Elsevier Inc.)

Background: Randomized controlled trials (RCTs) have demonstrated the efficacy and safety of P2Y12 inhibitor monotherapy following short-term dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). However, no studies have compared P2Y12 inhibitor and aspirin monotherapy following short-term DAPT. We aimed to compare available strategies for DAPT duration and post-DAPT antiplatelet monotherapy following PCI., Methods: Seven DAPT strategies [ticagrelor or clopidogrel following 1-month DAPT, ticagrelor following 3-month DAPT, aspirin following 3-6 months of DAPT (reference strategy), aspirin or P2Y12 inhibitor following 6-18-months of DAPT, and DAPT for ≥18 months] were compared using a network meta-analysis. The primary efficacy outcome was defined as a composite of all-cause death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding., Results: Our analysis identified 25 eligible RCTs, including 89,371 patients who underwent PCI. Overall, none of the strategies negatively affected the primary efficacy outcomes. For primary bleeding outcomes, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes (HR 0.73; 95 % CI 0.57-0.95). Clopidogrel following 1-month DAPT was also associated with a reduced risk of primary bleeding outcomes (HR 0.54; 95 % CI 0.34-0.85), however, the strategy was associated with an increased risk of myocardial infarction or stent thrombosis. Similar trends were observed among patients with acute coronary syndrome and high bleeding risk., Conclusions: Compared with aspirin monotherapy following short-term DAPT, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes without increasing any ischemic outcomes., Competing Interests: Declaration of competing interest Dr Kohsaka has received investigator-initiated grant funding from Novartis and personal fees from Bristol-Myers Squibb, Pfizer, and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Quantitative flow ratio (QFR) is a method for evaluating fractional flow reserve without the use of an invasive coronary pressure wire or pharmacological hyperemic agent., Objectives: The aim of this study was to investigate the prognostic implications of QFR and plaque characteristics in patients who underwent intravascular ultrasound (IVUS)-guided treatment for intermediate lesions., Methods: Among the IVUS-guided strategy group in the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial, vessels suitable for QFR analysis were included in this study. High-risk features were defined as low QFR (≤0.90), quantitative high-risk plaque characteristics (qn-HRPCs) (minimal lumen area ≤3.5 mm 2 , or plaque burden ≥70%), and qualitative high-risk plaque characteristics (ql-HRPCs) (attenuated plaque, positive remodeling, or plaque rupture) assessed using IVUS. The primary clinical endpoint was target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization., Results: A total of 415 (46.1%) vessels could be analyzable for QFR. The numbers of qn-HRPCs and ql-HRPCs increased with decreasing QFR. Among deferred vessels, those with 3 high-risk features exhibits a significantly higher risk of TVF compared with those with ≤2 high-risk features (12.0% vs 2.7%; HR: 4.54; 95% CI: 1.02-20.29)., Conclusions: Among the IVUS-guided deferred group, vessels with qn-HRPC and ql-HRPC with low QFR (≤0.90) exhibited a significantly higher risk for TVF compared with those with ≤2 features. Integrative assessment of angiography-derived fractional flow reserve and anatomical and morphological plaque characteristics is recommended to improve clinical outcomes in patients undergoing IVUS-guided deferred treatment., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from Boston Scientific and the Patient-Centered Clinical Research Coordinating Center (grant number: HI19C0481, HC19C0305). The funding agency had no role in the study design, analysis, interpretation of data, the writing of the manuscript, or the decision to submit the article for publication. Dr Hahn has received research grants from Abbott Korea, Biosensors International Group, Biotronik, Boston Scientific Corporation, and Medtronic. Dr Koo has received institutional research grant support from Abbott Vascular, Boston Scientific Corporation, and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic adversely affected health care systems. Patients in need of transcatheter aortic valve replacement (TAVR) are especially susceptible to treatment delays., Objectives: This study sought to evaluate the impact of the COVID-19 pandemic on global TAVR activity., Methods: This international registry reported monthly TAVR case volume in participating institutions prior to and during the COVID-19 pandemic (January 2018 to December 2021). Hospital-level information on public vs private, urban vs rural, and TAVR volume was collected, as was country-level information on socioeconomic status, COVID-19 incidence, and governmental public health responses., Results: We included 130 centers from 61 countries, including 65,980 TAVR procedures. The first and second pandemic waves were associated with a significant reduction of 15% (P < 0.001) and 7% (P < 0.001) in monthly TAVR case volume, respectively, compared with the prepandemic period. The third pandemic wave was not associated with reduced TAVR activity. A greater reduction in TAVR activity was observed in Africa (-52%; P = 0.001), Central-South America (-33%; P < 0.001), and Asia (-29%; P < 0.001). Private hospitals (P = 0.005), urban areas (P = 0.011), low-volume centers (P = 0.002), countries with lower development (P < 0.001) and economic status (P < 0.001), higher COVID-19 incidence (P < 0.001), and more stringent public health restrictions (P < 0.001) experienced a greater reduction in TAVR activity., Conclusions: TAVR procedural volume declined substantially during the first and second waves of the COVID-19 pandemic, especially in Africa, Central-South America, and Asia. National socioeconomic status, COVID-19 incidence, and public health responses were associated with treatment delays. This information should inform public health policy in case of future global health crises., Competing Interests: Funding Support and Author Disclosures Dr Lefèvre has served as a proctor for Edwards Lifesciences; and received minor fees from Boston Scientific, Terumo, and Abbott. Dr Pilgrim has received research, travel, or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; and speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr Van Mieghem has received research grant support from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Medtronic, Daiichi Sankyo, AstraZeneca, Teleflex; and advisory board fees from Abbott Vascular, Boston Scientific, Inari, JenaValve, Medtronic, Daiichi Sankyo, AstraZeneca, Siemens, Pie Medical, and Teleflex. Dr Swaans has served as a proctor/lecturer for Abbott Vascular, Boston Scientific, Bioventrix Inc, Cardiac Dimensions, Edwards Lifesciences, GE Healthcare, Medtronic, and Philips Healthcare. Dr Prendergast has received speaker/consultancy fees from Medtronic, MicroPort, Anteris, and Edwards Lifesciences. Dr Resar has received institutional research funding from Medtronic, Edwards Lifesciences, and Abbott; and served as a TAVR proctor for Medtronic. Dr Chen has served as a consultant for Venus MedTech. Dr Hildick-Smith has received research funds and speaker fees from Medtronic. Dr Spence has received TAVR proctoring and consultancy fees from Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Bunc has served as a proctor for Abbott, Meril, Edwards Lifesciences, and Medtronic. Dr Molnár has served as a consultant for Medtronic and Abbott. Dr Toggweiler has served as a consultant and proctor for Medtronic, Boston Scientific, and Biosensors; has served as a proctor for Edwards Lifesciences and Abbott Vascular; has served as a consultant for Medira, Shockwave, Teleflex, atHeart Medical, Cardiac Dimensions, and Polares Medical; has received institutional research grants from Boston Scientific, Fumedica, and Novartis; has received speaker honoraria from Sanofi, AstraZeneca, ReCor Medical, and Daiichi Sankyo; and holds equity in Hi-D Imaging. Dr Ojeda has received consulting fees from Medtronic and Edwards Lifesciences; and speaker fees from Philips and Word Medica. Dr Toutouzas has served as a proctor for Medtronic, Abbott, Myval, and Boston Scientific. Dr AlMerri has served as a TAVR proctor for Medtronic. Dr Noble has served as a proctor for Medtronic; and received institutional grant support from Edwards Lifesciences, Boston Scientific, Abbott Vascular, and Medtronic. Dr Kala has served as a consultant for Boston Scientific; served on the Speakers Bureau for Edwards Lifesciences, Servier, and AstraZeneca; and received research support from Novartis. Dr Kurt has served as a TAVR proctor for Abbott. Dr Yin has served as a TAVR proctor for Medtronic, Edwards Lifesciences, and Abbott. Dr Sztejfman has served as a proctor for Boston Scientific, Edwards Lifesciences, Medtronic, Meril Life Sciences, and MicroPort. Dr Mendiz has served as a proctor for Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Gunasekaran has received fees from Medtronic, Meril Life Sciences, Abbott, and Boston Scientific. Dr Kao has served as a proctor for Medtronic and Edwards Lifesciences. Dr Dager has served as a consultant for Medtronic. Dr Ferrero-Guadagnoli has served as a proctor for Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Modine has served as a consultant for and received honorarium from Abbott, Medtronic, and Edwards Lifesciences. Dr Hayashida has served as a proctor for Edwards Lifesciences, Medtronic, and Abbott. Dr Makkar has received research grants from Abbott, Edwards Lifesciences, and Boston Scientific, and served as a consultant for Cordis and Medtronic. Dr Mylotte has received institutional grant funding from Boston Scientific and Medtronic; and personal fees from Boston Scientific, Medtronic, and MicroPort. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Backgrounds: The HOST-EXAM Extended study reported the benefit of clopidogrel monotherapy over aspirin monotherapy in secondary prevention after percutaneous coronary intervention (PCI). This age-specific subgroup analysis of the study aimed to assess the impact of age on antiplatelet monotherapy after PCI., Methods: We analysed data from the per-protocol population (4717 patients) with a median follow-up of 5.8 years. The old age group comprised 2033 patients (43.1%), defined as those 65 years of age or older. The primary end point was the composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome (ACS), and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater. The secondary end points were thrombotic composite outcomes and any bleeding., Results: Age correlated with an elevated risk of adverse events, particularly from age 65. Clopidogrel monotherapy was associated with a reduction of the primary end point in both the old age group (19.4% vs 23.1%, hazard ratio [HR] 0.802, 95% confidence interval [CI] 0.664-0.968; P = 0.022) and the young age group (7.8% vs 11.7%, HR 0.646, 95% CI 0.506-0.825; P < 0.001), without significant interaction (interaction P = 0.167). These findings were consistent for the secondary composite thrombotic end point and any bleeding events (interaction P value of secondary thrombotic end point: 0.786; interaction P value of any bleeding end point: 0.565). Consistent results were observed in analyses with a 75-year age cutoff and in subgroup analyses by 10-year age intervals., Conclusions: In patients requiring antiplatelet monotherapy after PCI, occurrence of both ischemic and bleeding events dramatically increased from age 65. The beneficial impact of clopidogrel over aspirin monotherapy was consistent regardless of age., Clinical Trial Registration Information: ClinicalTrials.gov Identifier: NCT02044250., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Many patients require revascularization after index acute coronary syndrome (ACS). Lipoprotein(a) is thought to play a pathogenic role in atherothrombosis. In ODYSSEY OUTCOMES, alirocumab reduced major adverse cardiovascular events after ACS, with greater reduction among those with higher lipoprotein(a) levels. We explored whether risk of revascularization after ACS was modified by the level of lipoprotein(a) and treatment with alirocumab or placebo., Methods: In ODYSSEY OUTCOMES alirocumab was compared with placebo in 18,924 patients with ACS and elevated atherogenic lipoprotein levels despite optimized statin treatment. In this post hoc analysis, treatment effects are summarized using competing risks proportional hazard models., Results: A total of 1559 (8.2%) patients had coronary, 204 (1.1%) had limb, and 40 (0.2%) had carotid revascularization. Alirocumab reduced coronary revascularization (2.8 vs 3.2 events per 100 patient-years; hazard ratio [HR], 0.88 [95% confidence interval (CI), 0.80-0.97]; P = 0.01) and any revascularization (3.2 vs 3.7 events per 100 patient-years; HR, 0.85 [95% CI, 0.78-0.94]; P = 0.001). Baseline lipoprotein(a) quartile was directly associated with risk of coronary or any revascularization in the placebo arm and inversely related to treatment HRs (all P for trend < 0.01). Alirocumab produced the greatest reduction of coronary revascularization in patients with baseline lipoprotein(a) in the top quartile (≥ 59.6 mg/dL; HR, 0.69 [95% CI, 0.57-0.84]), but no apparent reduction in the bottom quartile (HR, 1.00 [95% CI, 0.82-1.22]). Findings were similar for the effect of alirocumab on any revascularization., Conclusions: Alirocumab reduced revascularization rates after ACS. The risk of revascularization and reduction in that risk with alirocumab were greatest in patients with elevated lipoprotein(a) at baseline., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although Medina 0.0.1 bifurcation lesions are often treated by percutaneous coronary intervention (PCI) in real-world practice, the optimal revascularization strategy for this lesion is uncertain., Objectives: The current study aimed to compare the clinical outcomes between 1- and 2-stent strategies in patients treated with PCI for Medina 0.0.1 bifurcation lesions., Methods: The extended BIFURCAT (Combined Insights From the Unified RAIN [Very Thin Stents for Patients with Left Main or Bifurcation in Real Life] and COBIS [Coronary Bifurcation Stenting] Bifurcation Registries) registry was obtained by patient-level merging the dedicated bifurcation COBIS II, III, and RAIN registries. Among 8,434 patients with bifurcation lesions undergoing PCI, 345 (4.1%) with Medina 0.0.1 lesions were selected for the current analysis. The primary endpoint was major adverse cardiac event (MACE, a composite of all-cause death, myocardial infarction, target vessel revascularization, and stent thrombosis) at 800 days., Results: In the total population, 209 patients (60.6%) received PCI with a 1-stent strategy and the remaining 136 patients (39.4%) with a 2-stent strategy. There was a tendency for higher use of a 1-stent strategy over time (36.0%, 47.4%, and 90.4% in 2003-2009, 2010-2014, and 2015-2017, respectively; P for trend < 0.001). For the treatment of Medina 0.0.1 lesions, there was no significant difference in the risk of MACE between 1- and 2-stent strategies (1 stent vs 2 stent, 14.3% vs 13.9%; HR: 1.034; 95% CI: 0.541-1.977; P = 0.92). The risk of MACE was also not significantly different when stratifying into 3 groups (1-stent crossover only, 1-stent with strut opening, and 2-stent strategy)., Conclusions: In patients with a Medina 0.0.1 type bifurcation lesion, PCI with a 1-stent strategy showed comparable outcomes to that of a 2-stent strategy. (Coronary Bifurcation Stenting II [COBIS II]; NCT01642992; Coronary Bifurcation Stenting III [COBIS III]; NCT03068494; Very Thin Stents for Patients with Left Main or Bifurcation in Real Life [RAIN]; NCT03544294)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Korean Bifurcation Club (COBIS III) and the Korean Society of Interventional Cardiology (COBIS II and III). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians., Objectives: This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes., Methods: From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure., Results: Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HR adj : 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HR adj : 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HR adj : 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HR adj : 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028)., Conclusions: Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events. (Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028)., Competing Interests: Funding Support and Author Disclosures The study was sponsored by the Platelet-Thrombosis Research Group under the Korean Society of Intervention Cardiology. Dr Jeong has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals; and research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr Joo has received honoraria for lectures from AstraZeneca, Hanmi, Samjin, Dong-A, HK inno. N Pharmaceuticals, and DIO Medical Ltd. Dr Song has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Sanofi, Bayer Korea, and Samjin Pharmaceutical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR)-related coronary artery obstruction prediction remains unsatisfactory despite high mortality and novel preventive therapies., Objectives: This study sought to develop a predictive model for TAVR-related coronary obstruction in native aortic stenosis., Methods: Preprocedure computed tomography and fluoroscopy images of patients in whom TAVR caused coronary artery obstruction were collected. Central laboratories made measurements, which were compared with unobstructed patients from a single-center database. A multivariate model was developed and validated against a 1:1 propensity-matched subselection of the unobstructed cohort., Results: Sixty patients with angiographically confirmed coronary obstruction and 1,381 without obstruction were included. In-hospital death was higher in the obstruction cohort (26.7% vs 0.7%; P < 0.001). Annular area and perimeter, coronary height, sinus width, and sinotubular junction height and width were all significantly smaller in the obstructed cohort. Obstruction was most common on the left side (78.3%) and at the level of the coronary artery ostium (92.1%). Coronary artery height and sinus width, but not annulus area, were significant risk factors for obstruction by logistic regression but performed poorly in predicting obstruction. The new multivariate model (coronary obstruction IF cusp height > coronary height, AND virtual valve-to-coronary distance ≤4 mm OR culprit leaflet calcium volume >600 mm 3 ) performed well, with an area under the curve of 0.93 (sensitivity = 0.93, specificity = 0.84) for the left coronary artery and 0.94 (sensitivity = 0.92, specificity = 0.96) for the right., Conclusions: A novel computed tomography-based multivariate prediction model that can be implemented routinely in real-world practice predicted coronary artery obstruction from TAVR in native aortic stenosis., Competing Interests: Funding Support and Author Disclosures This work was supported by a research grant from Medtronic to MedStar Cardiovascular Research Network and MedStar Health. Dr Kamioka has served as a proctor for Edwards Lifesciences. Dr Ludwig has received grant support from the German Heart Foundation; and received travel compensation from Edwards Lifesciences. Dr. Sinning has received speaker honoraria and research grants from Abbott, Abiomed, Medtronic, Boston Scientific, and Edwards Lifesciences; and served as a proctor for Medtronic and Boston Scientific. Dr Fuku has served as a proctor for Edwards Lifesciences and Medtronic. Dr Iyer has served as a proctor for Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Rodriguez has served as a speaker for Medtronic, Abbott, and Edwards Lifesciences. Dr Montorfano has served as a proctor for Edwards Lifesciences, Boston Scientific, and Abbott. Dr Ancona has received consulting fees from Abbott and Abiomed. Dr Ahmad has served as a proctor for Edwards Lifesciences. Dr Ruggiero has served as a proctor for Abbott and Edwards Lifesciences; served as a consultant for Abbott, Edwards Lifesciences, and RegenX-Bio; and received research support from Ancora Heart and Bard. Dr Weissman has served as the director of an academic cardiac computed tomography core lab with institutional contracts with Ancora Heart and LivaNova. Dr Waksman has served on the advisory board for Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd; has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd, Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc, and Venous MedTech; has received institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic, and Philips IGT; and is an investor in MedAlliance and Transmural Systems Inc. Dr Rogers has served as a proctor and consultant for Boston Scientific, Edwards Lifesciences, and Medtronic; has served on the advisory board for Medtronic; and holds equity interest in Transmural Systems Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Background: A limitation of the current guidelines regarding the timing of invasive coronary angiography for patients with non-ST-segment elevation acute coronary syndrome is the randomization time. To date, no study has reported the clinical outcomes of invasive strategy timing on the basis of the time of symptom onset., Objectives: The aim of this study was to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI)., Methods: Among 13,104 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health, 5,856 patients with NSTE myocardial infarction were evaluated. The patients were categorized according to symptom-to-catheter (StC) time (<48 or ≥48 hours). The primary outcome was 3-year all-cause mortality., Results: Overall, 3,919 patients (66.9%) were classified into the StC time <48 hours group. This group had lower all-cause mortality than the group with StC time ≥48 hours (7.3% vs 13.4%; P < 0.001). The lower risk for all-cause mortality in the group with StC time <48 hours group was consistent in all subgroups. Notably, emergency medical service use (HR: 0.31; 95% CI: 0.19-0.52) showed a lower risk for all-cause mortality than no emergency medical service use (HR: 0.54; 95% CI: 0.46-0.65; P value for interaction = 0.008)., Conclusions: An early invasive strategy on the basis of StC time was associated with a decreased risk for all-cause mortality in patients with NSTEMI. Because the study was based on a prospective registry, the results should be considered hypothesis generating, highlighting the need for further research. (iCReaT Study No. C110016)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The long-term prognostic implication of platelet reactivity after percutaneous coronary intervention (PCI) is not clearly known., Objectives: The impacts of platelet reactivity from the PTRG-DES consortium were assessed., Methods: The primary endpoint was the major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, myocardial infarction, stent thrombosis, or stroke. Key secondary endpoints were all-cause mortality, major bleeding, and net adverse clinical events (NACE), including MACCE and bleeding., Results: Between 2003 and 2018, a total of 11,714 patients were enrolled and grouped into tertiles according to P2Y 12 reaction units (PRUs): high PRUs (≥253), intermediate PRUs (188-252), and low PRUs (<188). The Kaplan-Meier (KM) estimates of the primary outcome were significantly different across the groups; the high-PRU group showed the highest MACCE rate at 5 years (12.9%, 11.1%, and 7.0% in high-, intermediate-, and low-PRU groups, respectively; P < 0.001), as well as at 1 year (P < 0.001). The high-PRU group had the greatest KM estimates of all-cause death (8.2%, 5.9%, and 3.7%, respectively; P < 0.001) at 5 years without significant differences of major bleeding, and resultant of a higher KM estimates of NACE (15.7%, 13.6%, and 9.7%, respectively; P < 0.001). A PRU ≥252, the best cutoff value, was strongly related to MACCE (HR: 1.39; 95% CI: 1.11-1.74; P = 0.003) and all-cause death at 5 years after PCI (HR: 1.42; 95% CI: 1.04-1.94; P = 0.026). The optimal cutoff value of aspirin reaction units predicting the MACCE occurrence was ≥414 and was significantly associated with 5-year MACCE occurrence or all-cause death (P < 0.001)., Conclusions: In this large-scale cohort, high PRU was significantly associated with occurrence of MACCE, all-death death, and NACE at 5 years, as well as 1 year after PCI. (PTRG-DES Consortium [PTRG]; NCT04734028)., Competing Interests: Funding Support and Author Disclosures The study was designed by the principal investigator and executive committee and was sponsored by the Korean Society of Intervention Cardiology. The funder had no role in study design, data collection, analyses, data interpretation, or preparing the manuscript. Dr Jeong has received honoraria for lectures from AstraZeneca, Daiichi-Sankyo, Sanofi, Han-mi Pharmaceuticals, and Yuhan Pharmaceuticals; and has received research grants or support from Yuhan Pharmaceuticals and U&I Corporation. Dr Joo has received honoraria for lectures from AstraZeneca, Han-mi Pharmaceuticals, Samjin, Dong-A, HK inno.N Pharmaceuticals, and DIO Medical. Dr Song has received honoraria for lectures from AstraZeneca, Daiichi-Sankyo, Sanofi, Bayer Korea, and Samjin Pharmaceutical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Resolute Onyx polymer-based zotarolimus-eluting stents (ZES) were noninferior in safety and effectiveness to BioFreedom polymer-free biolimus A9-coated stents (DCS) in high-bleeding-risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) at 1 year., Objectives: This study reports the final 2-year results of the randomized Onyx ONE trial., Methods: The Onyx ONE (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) trial randomly assigned HBR patients to treatment with ZES or DCS. Following 1-month DAPT, event-free patients received SAPT (either aspirin or a P2Y 12 inhibitor at physician discretion). The primary safety endpoint, a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year, was determined at 1 year. Rates of primary and secondary endpoints were calculated after final follow-up at 2 years., Results: A total of 1,003 patients were randomly allocated to ZES and 993 patients to DCS. Follow-up was complete in 980 (97.7%) ZES patients and 962 (96.9%) DCS patients at 2 years. The primary safety endpoint occurred in 208 (21.2%) patients in the ZES group and 199 (20.7%) patients in the DCS group (risk difference: 0.5%; 95% CI: -3.1% to 4.2%; P = 0.78) at 2 years without significant differences in individual components of the composite endpoint. The secondary effectiveness endpoint occurred in 217 (22.1%) patients in the ZES group and 202 (21.0%) patients in the DCS group (risk difference: 1.1%; 95% CI: -2.5% to 4.8%; P = 0.54)., Conclusions: Among patients at HBR treated with 1-month DAPT followed by SAPT, the Resolute Onyx polymer-based ZES had similar 2-year outcomes for the primary safety and secondary effectiveness endpoint compared with the BioFreedom polymer-free DCS. (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy [DAPT] for High-Bleeding Risk Patients [Onyx ONE]; NCT03344653)., Competing Interests: Funding Support and Author Disclosures The Onyx ONE trial was sponsored by Medtronic. Dr Windecker has received research and educational grants to the institution from Abbott, Amgen, AstraZeneca, BMS, Bayer, Biotronik, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi, Sinomed, Terumo, and V-Wave; served as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, BMS, Boston Scientific, Biotronik, CardioValve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments by pharmaceutical companies or device manufacturers; and has served as a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Latib has received consulting fees from Medtronic, Abbott Vascular, and Boston Scientific. Dr Kedhi has received speaker honoraria and institutional grants from Medtronic and Abbott Vascular. Dr Kirtane has received institutional funding to Columbia University and/or the Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, and Neurotronic (in addition to research grants, institutional funding includes fees paid to Columbia University and/or the Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr Kirtane controlled the content); has served as a consultant for IMDS; and has received travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr Kandzari has received institutional research or grant support from Abbott Vascular, Biotronik, Boston Scientific, Cardiovascular Systems, Orbus Neich, Medtronic, and Ablative Solutions; and has received personal consulting honoraria from Cardiovascular Systems, Magenta Medical, and Medtronic. Dr Mehran has received institutional research grants from Abbott Laboratories, Abiomed, Applied Therapeutics, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received consulting fees from Abbott Laboratories, Boston Scientific, CardiaWave, Chiesi, Cine-Med Research, Janssen Scientific Affairs, Medscape/WebMD, Medtelligence (Janssen Scientific Affairs), Roivant Sciences, Sanofi, and Siemens Medical Solutions; has received consultant fees paid to the institution from Abbott Laboratories and Bristol Myers Squibb; has served on the advisory board, with funding paid to the institution, for Spectranetics/Philips/Volcano Corp; has a spouse who has served as a consultant for Abiomed, The Medicines Company, Merck; Equity <1% from Claret Medical, Elixir Medical, Applied Therapeutics, and STEL; has received Data Safety and Monitoring Board Membership fees paid to the institution from Watermark Research Partners; has served as a consultant (no fee) for Idorsia Pharmaceuticals and Regeneron Pharmaceuticals; and has served as an Associate Editor for the American College of Cardiology and the American Medical Association. Dr Price has received consulting fees and speaker honoraria from AstraZeneca, Abbott Vascular, Boston Scientific, and Medtronic; and has received consulting fees from Acutus, Baylis Medical, and W.L. Gore. Dr Simon has received honoraria for serving as a course director (<$10,000) from Medtronic. Dr Worthley has received institutional grant or research support from Abbott and Biotronik. Dr Zaman has received consulting fees from Abbott, Boston Scientific, Medtronic, Meril, SMT, and Terumo. Dr Petrov has received consulting, proctor, or speaker fees from Medtronic, Edwards, Philips, Cardiatis, Boehringer Ingelheim, Servier, and Pfizer. Dr Mylotte has received consulting fees from Medtronic, Boston Scientific, and MicroPort. Dr Moreno has received lecture or consulting fees from Medtronic, Biosensors, Abbott Vascular, Boston Scientific, Terumo, and Braun. Dr Pasupati has received consulting, proctor, or speaker fees from Medtronic, Edwards, Boston Scientific, JenaValve, BioExcel, Boehringer Ingelheim, and Pfizer. Dr Kim has received research grants through Seoul National University Hospital from Abbott, Medtronic, Biotronik, B. Braun, and Daiichi-Sankyo; and has received lecture and consulting fees from Edwards Lifesciences, Medtronic, Novartis, Pfizer, Daiichi-Sankyo, AmGen, AstraZeneca, and Boehringer Ingelheim. Dr Tie has received speaker fees from Boehringer Ingelheim, outside the submitted work. Dr Hur has received research grants from Boston Scientific and Terumo. Dr Marx has received an honorarium for Clinical Events Committee membership from the Cardiovascular Research Foundation. Dr Ali has received institutional grant support from Abiomed, Acist Medical, Abbott, Boston Scientific, Cardiovascular Systems, Philips, and Opsens Medical; has received consulting or advisory fees from Amgen and Boston Scientific; has received speaker honoraria from AstraZeneca; and owns equity in Shockwave Medical. Ms. Parke and Dr Lung are employees of Medtronic. Dr Stone has received speaker honoraria from Cook, Infraredx, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Reva, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; and owns equity or options in Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and the MedFocus family of funds. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Current treatment guidelines for acute myocardial infarction (AMI) recommend lowering low density lipoprotein cholesterol (LDL-C). However, previous clinical studies among East Asian AMI patients failed to prove its clinical efficacy of lipid lowering therapy based on Western target LDL-C level. Thus, the purpose of this study is directly to compare the clinical outcomes of target LDL-C < 70 mg/dL and < 55 mg/dL and identify optimal target LDL-C level and in Korean AMI patients., Methods and Results: A total of 2198 AMI patients in Korea AMI Registry - National Institute of Health were enrolled. Patients were initially divided into LDL-C non-target group (n = 1115) and target group (n = 1083). Successful achievement of follow up target LDL-C was defined as <70 mg/dL and ≥ 50% reduction from baseline. Target group patients were additionally divided to <70 mg/dL group (n = 698) and <55 mg/dL group (n = 385). Propensity score matching analysis was done in non-target vs. target group and <70 mg/dL vs. <55 mg/dL group. In the matched population, the risk of 3 years major adverse cardiac event (MACE) (13.0% vs 9.8%, HR: 0.73; 95% CI: 0.56-0.96; p = 0.025) was higher in non-target group patients. However, the risk of MACE was similar in <70 mg/dL and < 55 mg/dL group patients (10.0% vs 8.1%, HR: 0.75, 95% CI: 0.46-1.22; p = 0.247)., Conclusion: In the present study, target LDL-C level of <70 mg/dL and ≥ 50% reduction from baseline level was associated with better clinical outcomes in Korean AMI patients. However, further lowering target LDL-C level of <55 mg/dL showed no additional benefits., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to determine whether side branch (SB) wire jailing before main vessel (MV) stenting could prevent SB occlusion after the 1-stent strategy for bifurcation percutaneous coronary intervention., Background: The benefits of SB wire jailing in the 1-stent strategy remain unclear., Methods: From the COBIS (Coronary Bifurcation Stenting) III registry, 1,890 patients with bifurcation lesions who underwent the 1-stent strategy using second-generation drug-eluting stents were identified and classified into 2 groups according to the use of SB wire jailing: wire jailing (n = 819) and non-wire jailing (n = 1,071). The incidence of SB occlusion (Thrombolysis In Myocardial Infarction flow grade <3) and target lesion failure (cardiac death, myocardial infarction, or target lesion revascularization) was compared., Results: The incidence of final SB occlusion was not significantly different between wire jailing (1.8%) vs non-wire jailing (2.9%; P = 0.182). However, wire jailing at the SB was a significant protective factor for SB occlusion after MV stenting on multivariate analysis and was significantly associated with a lower incidence of SB occlusion in patients with significant stenoses (≥60%) at the SB (5.1% vs 11.3%; odds ratio: 0.42; 95% CI: 0.19-0.89; P = 0.028) or MV (3.1% vs 6.2%; odds ratio: 0.49; 95% CI: 0.24-0.95; P = 0.039). During follow-up (median 52 months), the incidence of target lesion failure was not significantly different between wire jailing and non-wire jailing (7.6% vs 6.3%; P = 0.343)., Conclusions: During bifurcation percutaneous coronary intervention with the 1-stent strategy, wire jailing at the SB was associated with a lower rate of final SB occlusion following MV stenting in patients with severe stenoses at the SB or MV but not with overall bifurcation lesions. Long-term clinical outcomes were comparable between the 2 groups., Competing Interests: Funding Support and Author Disclosures This work was supported by the Korean Bifurcation Club, Korean Society of Interventional Cardiology, and Cardiovascular Research Center, Seoul, Republic of Korea. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The ideal drug-eluting stent (DES) for the treatment of unprotected left main coronary artery (ULMCA) is unknown. We compared percutaneous coronary intervention (PCI) using durable polymers versus early-generation, thicker strutted and coated bioabsorbable polymers for ULMCA disease., Methods: Patients who underwent ULMCA PCI (893 patients) from April 2008 to November 2014 were identified from the Grand-DES registry. The primary end point was 3-year target lesion failure (TLF) after propensity score matching., Results: The final analysis included 754 patients (84.4%) and 139 patients (15.6%) in the durable and bioabsorbable polymer group, respectively. The groups differed significantly in lesion and procedural characteristics. Propensity score-matched analysis revealed a trend toward a lower 3-year TLF in the durable polymer group (log rank p=0.071). Independent predictors of 3-year TLF were chronic kidney disease, presentation with acute myocardial infarction, and a two-stenting technique for ULMCA lesions. Definite/probable stent thrombosis rates at 3-years were low in both groups (0.8% vs. 0.7%, p=0.925)., Conclusions: The safety of ULCMA PCI was excellent, and durable and bioabsorbable polymer DES provided similar clinical outcomes at 3-year follow-up. Landmark analysis revealed that the durable polymer group had a lower TLF rate from 9 months. Further studies are needed to confirm these results., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population., Methods: We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250., Findings: Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035)., Interpretation: Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events., Funding: ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare., Competing Interests: Declaration of interests H-SK has received research grants or speaker's fees from Medtronic, Abbott Vascular, Edwards Life Science, Boston Scientific, Terumo, Biotronik and Dio, AmGen, Pfizer, AstraZeneca, MSD, Daiichi Sankyo, and Boehringer Ingelheim. B-KK has received institutional research grants from Abbott Vascular and Philips. KWP reports fees from Daiichi Sankyo, AstraZeneca, Sanofi, Bristol-Myers Squibb, Bayer, and Pfizer outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Variations by hospital and region in the selection of an early invasive strategy (EIS) after non-ST-segment elevation myocardial infarction (NSTEMI) in patients with high-risk criteria are unknown., Methods: We evaluated the data of 7037 patients with NSTEMI from 20 hospitals of 3 regions from the Korean Acute Myocardial Infarction Registry-National Institute of Health database. We used hierarchical generalized linear mixed-models to estimate region- and hospital-level variation in the selection of an EIS after adjusting for patient-level high-risk criteria. We explored the variation using the median rate ratio (MRR), which estimates the relative difference in the risk ratios of two hypothetically identical patients at two different sites., Results: An EIS was selected in 84.4% of patients. At the hospital level, the median selection rate was 80.4%. At the region level, the median selection rate was 74.9% in the east region, 81.3% in the north region, and 83.9% in the west region, respectively. After adjusting for patient-level covariates, we found significant hospital- (MRR 2.19, 95% confidence interval [CI]: 1.74-3.03) and region-level (MRR 1.88, 95%CI: 1.26-5.44) variation in the selection of an EIS. Among patient-level factors, male sex, ongoing chest pain, history of coronary artery disease or acute heart failure, and GRACE risk score > 140 were independently associated with the selection of an EIS., Conclusions: We observed significant hospital- and region-level variation in the selection of an EIS after NSTEMI in high-risk patients. Quality improvement efforts are required to standardize decision making and to improve clinical outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy., Methods: HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971., Results: From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference -2·9%, p non-inferiority <0·0001; hazard ratio 0·70 [95% CI 0·52-0·92], p equivalence =0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 [0·40-1·45]; p=0·40), and the risk of bleeding events was significantly decreased (0·48 [0·32-0·73]; p=0·0007)., Interpretation: In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia., Funding: Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: Approximately half of cases of cardiovascular disease (CVD) worldwide occur in Asia, with acute coronary syndrome (ACS) a leading cause of mortality. Long-term ACS-related outcomes data in Asia are limited. This analysis examined 2-year ACS-related outcomes in patients enrolled in the EPICOR Asia study, and the association between patient characteristics and management on outcomes., Methods: EPICOR Asia is a multinational, prospective, primary data collection study of real-world management of Asian patients with ACS. Overall, 12,922 eligible adults (hospitalized for ACS within 48 h of symptom onset and who survived to discharge) were enrolled from 219 centers in eight Asian countries. Patients were followed up post-discharge for 2 years and clinical outcomes recorded., Results: Patients were of mean age 60 years and 76% were male. Diagnoses were STEMI (51.2%), NSTEMI (19.9%), and UA (28.9%). During follow-up, 5.2% of patients died; NSTEMI patients had the highest risk profile. Mortality rate (adjusted HR [95% CI]) was similar in NSTEMI (0.97 [0.81-1.17]) and lower in UA (0.52 [0.33-0.82]) vs STEMI. Similar trends (adjusted) were seen for the composite endpoint of death, myocardial infarction, or ischemic stroke, and bleeding rates did not differ significantly. For all three diagnoses, patients who were medically managed had a markedly elevated risk of both death and the composite endpoint., Conclusions: During 2-year follow-up, adjusted risks of mortality, the composite endpoint, and bleeding rates were similar in NSTEMI and STEMI patients. Outcomes risk was better for invasive management. Long-term management strategies in Asia need to be optimized., Competing Interests: Declaration of Competing Interest Yong Huo, Stephen W-L Lee, Jitendra PS Sawhney, Hyo-Soo Kim, Ángeles Alonso-Garcia, Jie Jiang, and Stephen Jan have nothing to disclose. Rungroj Krittayaphong has been a consultant or advisory board member for AstraZeneca and Boehringer Ingelheim. Stuart J Pocock receives research funds from AstraZeneca. Vo T Nhan has received research grants from AstraZeneca, Servier, Sanofi, and Boston Scientific, and has been a consultant or advisory board member for AstraZeneca, Pfizer, Sanofi, Boehringer Ingelheim, Servier, MSD, Abbott, Bayer, Novartis, Merck Serono, Biosensor, Biotronic, Boston Scientific, Terumo, and Medtronic. Chee Tang Chin has received research support from Eli Lilly and honoraria from Medtronic, and has been a consultant or advisory board member for AstraZeneca. Ana M Vega was a former employee of AstraZeneca and Nobuya Hayashi is a current employee of AstraZeneca. Tiong Kiam Ong has acted as a consultant or advisory board member for Sanofi-Aventis, Abbott Vascular, Boston Scientific, Boehringer Ingelheim, Novartis, and AstraZeneca., (Copyright © 2020. Published by Elsevier B.V.)

Background: Cardiovascular diseases account for approximately half of all deaths in Asia. The present analysis aimed to evaluate characteristics, antithrombotic management patterns (AMPs), and outcomes in patients with acute coronary syndrome (ACS) who underwent in-hospital percutaneous coronary intervention (PCI) and survived to hospital discharge, using data from the EPICOR Asia registry (NCT01361386)., Methods: Two-year post-discharge follow-up data were analyzed from 8757 ACS PCI patients from EPICOR Asia (218 centers, eight countries). Major adverse cardiovascular events (MACE; death, non-fatal myocardial infarction [MI], non-fatal ischemic stroke), PCI characteristics, and AMPs were recorded. For MACE, time - to - event was analyzed using Cox regression., Results: Primary PCI was performed in 62.0% of ST-segment elevation MI (STEMI), 38.7% of non-STEMI (NSTEMI), and 24.2% of unstable angina (UA) patients. At 12 months, 88.1% of patients were on dual antiplatelet therapy (DAPT), with no differences by index event. Most (61.5%) still received DAPT at 2 years. Two-year incidences of mortality, composite MACE, and bleeding were 3.6%, 6.2%, and 6.6%, respectively. Risk of death and MACE was increased with STEMI and NSTEMI vs. UA. Patients from East Asia showed lower mortality and more bleeding vs. Southeast Asia/India., Conclusions: Many patients in EPICOR Asia underwent PCI and received DAPT up to 2 years post-discharge. These real-world findings improve our understanding of AMP impact on outcomes in Asian patients with ACS undergoing PCI., Competing Interests: Declaration of competing interest S.Z., W.W., J.P.S.S., H.S.K., S.W.L.L., Y.H., J.Q., and J.G. declare no conflict of interest. R.K. reports having been a consultant or advisory board member for AstraZeneca and Boehringer Ingelheim (both modest). V.T.N. reports research grants from AstraZeneca, Servier, Sanofi, and Boston Scientific, and has been a consultant or advisory board member for AstraZeneca, Pfizer, Sanofi, Boehringer Ingelheim, Servier, MSD, Abbott, Bayer, Novartis, Merck Serono, Biosensor, Biotronic, Boston Scientific, Terumo, and Medtronic (all modest). T.K.O. reports having acted as a consultant or advisory board member for Sanofi-Aventis, Abbott Vascular, Boston Scientific, Boehringer Ingelheim, Novartis, and AstraZeneca (all modest). C.T.C. reports research support from Eli Lilly, honoraria from Medtronic, and has been a consultant or advisory board member for AstraZeneca (all modest). S.J.P. reports receiving research funds from AstraZeneca (modest)., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: The aim of this study was to investigate the safety and efficacy of coronary protection by preventive coronary wiring and stenting across the coronary ostia in patients at high risk for coronary obstruction after transcatheter aortic valve replacement (TAVR)., Background: Coronary obstruction following TAVR is a life-threatening complication with high procedural and short-term mortality., Methods: Data were collected retrospectively from a multicenter international registry between April 2011 and February 2019., Results: Among 236 patients undergoing coronary protection with preventive coronary wiring, 143 had eventually stents implanted across the coronary ostia after valve deployment. At 3-year follow-up, rates of cardiac death were 7.8% in patients receiving stents and 15.7% in those not receiving stents (adjusted hazard ratio: 0.42; 95% confidence interval: 0.14 to 1.28; p = 0.13). There were 2 definite stent thromboses (0.9%) in patients receiving stents, both occurring after TAVR in "valve-in-valve" procedures. In patients not receiving stents, there were 4 delayed coronary occlusions (DCOs) (4.3%), occurring from 5 min to 6 h after wire removal. Three cases occurred in valve-in-valve procedures and 1 in a native aortic valve procedure. Distance between the virtual transcatheter valve and the protected coronary ostia <4 mm was present in 75.0% of patients with DCO compared with 30.4% of patients without DCO (p = 0.19)., Conclusions: In patients undergoing TAVR at high risk for coronary obstruction, preventive stent implantation across the coronary ostia is associated with good mid-term survival rates and low rates of stent thrombosis. Patients undergoing coronary protection with wire only have a considerable risk for DCO., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome remains uncertain. This study investigated the benefit of DAPT beyond 12 months after drug-eluting stents (DES) for acute myocardial infarction (MI)., Methods: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 6199 patients treated with DAPT for 12 months after DES (second-generation DES 98%) without ischemic or bleeding events were analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of death from any cause, MI, or ischemic stroke during the period from 12 to 24 months., Results: After adjustment using inverse probability of treatment weighting, patients who received DAPT beyond 12 months (n=4795), compared to patients treated with 12-month DAPT (n=1404), had a similar incidence of MACCE (1.3% vs. 1.0%, HR: 1.32, 95% CI: 0.71-2.45, p=0.378). The 2 groups did not differ significantly in the rates of death (0.1% vs. 0.1%), MI (0.8% vs.0.6%), stent thrombosis (0.1% vs. 0.2%), ischemic stroke (0.4% vs. 0.2%), and major bleeding (0.1% vs. 0.1%). The rate of net adverse clinical events was 1.4% with DAPT beyond 12 months and 1.1% with 12-month DAPT (p=0.466)., Conclusions: DAPT beyond 12 months, as compared with 12-month DAPT, in real-world patients with acute MI treated predominantly with second-generation DES did not reduce the risk of MACCE. The rates of major bleeding and net adverse clinical events did not differ significantly between the 2 treatments., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: The authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS)., Background: ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known., Methods: Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR CT ], change in FFR CT across the lesion [△FFR CT ], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR CT , △FFR CT , WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC)., Results: The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFR CT and higher △FFR CT , WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001)., Conclusions: Noninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Potent P2Y12 blockers are preferred in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). However, the risk of bleeding remains a major concern. We assessed the association of potent P2Y12 blockers with ischemic and bleeding outcomes in patients with NSTEMI., Methods: From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 4927 patients with NSTEMI receiving drug-eluting stents (DES) were divided into potent P2Y12 blocker (ticagrelor or prasugrel, n=901) and clopidogrel (n=3180) groups. Propensity-matched 12-month ischemic and bleeding events were compared. Patients who received anticoagulants or who discontinued P2Y12 blockers or switched between potent P2Y12 blockers and clopidogrel were excluded., Results: In the overall population, patients at higher ischemic and bleeding risks more often received clopidogrel. After propensity matching (n=901 in each group), 12-month rates of major adverse cardiac and cerebrovascular events were lower (7.3% vs. 10.1%, p=0.038), but Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were higher (5.9% vs. 2.2%, p<0.001) with potent P2Y12 blockers. Twelve-month rates of death from any cause, MI, stroke, or TIMI major bleeding were not different. On multivariate analysis, 12-month risk of TIMI major or minor bleeding was higher with B2 or C lesion, potent P2Y12 blocker use, body weight <60kg, and lower with time to PCI <12h and radial artery access., Conclusions: In patients with NSTEMI receiving DES, potent P2Y12 blockers were associated with reduced ischemic but increased bleeding risk with similar net clinical benefits., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: The aim of this study was to investigate clinical outcomes after left main coronary artery (LM) bifurcation percutaneous coronary intervention (PCI) and the impact of the duration of dual antiplatelet therapy (DAPT) according to treatment strategy., Background: There are limited data regarding the optimal PCI strategy for LM bifurcation lesions with new-generation drug-eluting stents., Methods: A patient-level pooled analysis of 5 nationwide multicenter registries was performed. Rates of target lesion failure, thrombotic adverse cardiovascular events, and their individual components at 3-year were analyzed. Subgroup analysis according to DAPT duration was performed., Results: From 13,172 patients undergoing PCI with new-generation drug-eluting stents, a total of 700 patients were treated for LM bifurcation lesions, 567 with a 1-stent strategy and 133 with a 2-stent strategy. Rates of target lesion failure and target lesion revascularization were higher in the 2-stent group, driven mainly by complex lesion profiles. Risks for thrombotic adverse cardiovascular events and its components were comparable between the 2 strategies. Subgroup analysis showed that risks for target lesion failure and thrombotic adverse cardiovascular events in the 2-stent group were significantly higher than in the 1-stent group in those with DAPT interruption <1 year, while they were similar in those receiving DAPT maintenance ≥1 year., Conclusions: Up to 20% of patients who underwent LM bifurcation PCI eventually required a 2-stent strategy, which was as safe as a 1-stent strategy with the use of new-generation drug-eluting stents. Careful pre-emptive case selection as well as prolonged DAPT may be necessary when considering a 2-stent strategy in LM PCI given its higher rate of repeat revascularization and lesion failure than the 1-stent approach., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ventricular tachycardia or fibrillation (VT/VF) is a major cause of sudden cardiac death after acute myocardial infarction (AMI). This study aims to investigate the clinical characteristics and outcomes of VT/VF, to identify the variables associated with VT/VF, and to construct a new scoring system., Methods: Patients with relatively preserved left ventricular ejection fraction (LVEF) (≥40%) included in the Korea Acute Myocardial Infarction Registry-National Institutes of Health registry were enrolled in this study. Among 13,109 patients in the registry, a total of 10,334 (78.8%) had relatively preserved LVEF after AMI. Patients were divided into two groups based on whether they experienced life-threatening VT/VF during hospitalization or not. The predictors for VT/VF during hospitalization were assessed. In-hospital mortality and complications were recorded., Results: A total of 358 (3.5%) experienced life-threatening VT/VF. The VT/VF group was at an increased risk of in-hospital mortality (odds ratio 2.99) and cardiac death (odds ratio 3.40). Variables of diagnosis, Killip class, smoking, initial rhythm, left bundle branch block, and LVEF were significant indicators of VT/VF. A new risk score system yielded acceptable discrimination function (c-statistics=0.773)., Conclusions: Relatively preserved LVEF patients could still be at risk of life-threatening VT/VF, which is related to a poor prognosis during the admission period. This new scoring system can be adopted to stratify the risk of VT/VF., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Dual antiplatelet therapy (DAPT) is recommended in patients receiving drug-eluting stents (DES). However, bleeding risk should be weighed against ischemic risk. Utility of GRACE risk score and ACUITY-HORIZONS bleeding risk score was assessed in patients with acute myocardial infarction (MI) according to use of P2Y12 blocker., Methods: From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 7791 patients with acute MI receiving DES were divided into ticagrelor (n=1554) and clopidogrel (n=6237) groups. Propensity-matched 12-month mortality and bleeding event rates were compared according to GRACE and ACUITY-HORIZONS scores. Patients who received thrombolysis, prasugrel or anticoagulants, or who discontinued or switched DAPT were excluded., Results: In all patients, high-risk patients more often received clopidogrel. After propensity score matching (n=1553 in each group), 12-month mortality was not different, but TIMI major bleeding rate was higher with ticagrelor (2.8% vs. 1.4%, p=0.007). On subgroup analysis, 12-month mortality was lower with ticagrelor in patients with high (>140) compared to low-to-moderate risk GRACE score (5.1% vs. 7.9%, p=0.04). When combined with ACUITY-HORIZONS bleeding score, 12-month mortality was lower with ticagrelor in patients with high GRACE score but without very high (≥20) ACUITY-HORIZONS score (2.4% vs. 5.3%, p=0.03)., Conclusions: In patients with acute MI receiving DES, GRACE and ACUITY-HORIZONS scores may help guide DAPT. In patients with high GRACE score, a more potent P2Y12 blocker may be considered, particularly in the subset not at very high risk of bleeding., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The correlation between obesity and metabolic syndrome (MetS) and its impact on cardiovascular disease remains unclear. This study aims to investigate the impact of metabolic status and obesity on clinical outcomes of male patients with ST-segment elevation myocardial infarction (STEMI)., Methods: Data from the Korea Acute Myocardial Infarction Registry-National Institutes of Health registry were used to evaluate the impact of obesity and MetS on patients undergoing primary percutaneous coronary intervention (PPCI) from November 2005 to November 2015. Patients were grouped according to the presence or absence of obesity and MetS ('obese-/MetS-', 'obese-/MetS+', 'obese+/MetS-', or 'obese+/MetS+', respectively). All-cause death and major adverse cardiac events (MACE) were recorded during 12 months of follow-up., Results: A total of 14,357 patients were included. Multivariate analysis showed that the presence of MetS was an independent risk factor for all-cause death (HR 2.08, 95% CI 1.30-3.31, p=0.002) and cardiovascular death (HR 2.44, 95% CI 1.33-4.46, p=0.004) at 12 months among normal weight patients. The protective effect of obesity was observed, compared with the obese-/MetS+ group, in terms of all-cause death (HR 0.50, 95% CI 0.31-0.81, p=0.005) and cardiovascular death (HR 0.52, 95% CI 0.28-0.96, p=0.038; vs. total obese individuals), but it might have disappeared compared with the obese-/MetS- group. The rate of MACE did not differ significantly according to category by obesity and MetS., Conclusions: The obesity paradox has not been observed between obese and normal weight patients without MetS. Risk stratification on the basis of the presence or absence of MetS is not a clinically useful indicator of outcome in obese male patients with STEMI after PPCI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the impact of optimizing procedure-related factors during drug-eluting balloon (DEB) angioplasty on clinical outcomes of drug-eluting stent in-stent restenosis (ISR)., Background: Although DEB angioplasty is recommended as a reasonable option for ISR, recurrent target lesion failure (TLF) still occurs in many patients after DEB angioplasty., Methods: Consecutive patients with drug-eluting stent ISR treated with DEB (SeQuent Please) were collected from 4 centers in Korea. The primary outcome was 2-year TLF. Procedure-related modifiable independent predictors for TLF and their best cutoff values were determined., Results: In a total of 256 patients (309 lesions), TLF occurred in 52 patients (20.3%). Modifiable independent predictors of TLF among procedure-related factors were residual diameter stenosis after lesion preparation (residual percentage diameter stenosis [%DS]), DEB-to-stent ratio (BSR), and DEB inflation time (T inflation ), whose best cutoff values were 20%, 0.91, and 60 s, respectively. TLF rates were significantly higher in groups with residual %DS ≥20% (34.7% vs. 12.5%; adjusted hazard ratio: 2.15; 95% confidence interval: 1.86 to 2.48; p < 0.001), BSR ≤0.91 (46.4% vs. 21.9%; adjusted hazard ratio: 2.02; 95% confidence interval: 1.75 to 2.34; p < 0.001), and T inflation  ≤60 s (26.2% vs. 14.0%; adjusted hazard ratio: 1.82; 95% confidence interval: 1.36 to 2.45; p < 0.001). When classifying ISR lesions by combination of procedure-related factors, TLF occurred in 8.3% in the fully optimized procedure group (residual %DS <20%, BSR >0.91, and T inflation >60 s) and 66.7% in the nonoptimized group (residual %DS ≥20%, BSR ≤0.91, and T inflation  ≤60 s) (p < 0.001)., Conclusions: Residual %DS after lesion preparation, BSR, and T inflation were the only modifiable procedure-related factors in DEB angioplasty. Fully optimized DEB angioplasty with optimal lesion preparation, prolonged inflation, and sufficient dilation may play an important role in reducing TLF after DEB angioplasty., (Copyright © 2018. Published by Elsevier Inc.)

Background: Limited data exist regarding the impact of aortic valve calcification (AVC) eccentricity on the risk of paravalvular regurgitation (PVR) and response to balloon post-dilation (BPD) after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value of AVC eccentricity in predicting the risk of PVR and response to BPD in patients undergoing TAVR., Methods: We analyzed 85 patients with severe aortic stenosis who underwent self-expandable TAVR (43 women; 77.2±7.1years). AVC was quantified as the total amount of calcification (total AVC load) and as the eccentricity of calcium (EoC) using calcium volume scoring with contrast computed tomography angiography (CTA). The EoC was defined as the maximum absolute difference in calcium volume scores between 2 adjacent sectors (bi-partition method) or between sectors based on leaflets (leaflet-based method)., Results: Total AVC load and bi-partition EoC, but not leaflet-based EoC, were significant predictors for the occurrence of ≥moderate PVR, and bi-partition EoC had a better predictive value than total AVC load (area under the curve [AUC]=0.863 versus 0.760, p for difference=0.006). In multivariate analysis, bi-partition EoC was an independent predictor for the risk of ≥moderate PVR regardless of perimeter oversizing index. The greater bi-partition EoC was the only significant parameter to predict poor response to BPD (AUC=0.775, p=0.004)., Conclusion: Pre-procedural assessment of AVC eccentricity using CTA as "bi-partition EoC" provides useful predictive information on the risk of significant PVR and response to BPD in patients undergoing TAVR with self-expandable valves., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: This study sought to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after the implantation of a drug-eluting stent (DES) in elderly patients., Background: Qualified studies to evaluate the optimal duration of DAPT in elderly patients have been very limited., Methods: Using 6 randomized trials that compared short-term (≤6 months) and long-term (12 months) DAPT, individual participant data meta-analysis was performed in elderly patients (≥65 years of age). The primary study outcome was the 12-month risk of a composite of myocardial infarction, definite or probable stent thrombosis, or stroke. The major secondary outcome was the 12-month risk of major bleeding., Results: The primary outcome risk did not significantly differ between patients receiving short-term and long-term DAPT (hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.88 to 1.43; p = 0.3581) in the overall group of study participants. In subgroup analysis, a significant interaction between age and DAPT duration was observed for primary outcome risk (p for interaction = 0.0384). In the subset of younger patients (<65 years of age, n = 6,152), short-term DAPT was associated with higher risk of primary outcome (HR: 1.67; 95% CI: 1.14 to 2.44; p = 0.0082). In elderly patients (n = 5,319), however, the risk of primary outcome did not significantly differ between patients receiving short-term and long-term DAPT (HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.2856). Short-term DAPT was associated with a significant reduction in major bleeding compared with long-term DAPT (HR: 0.50; 95% CI: 0.30 to 0.84; p = 0.0081) in the overall group, and particularly in elderly patients (HR: 0.46; 95% CI: 0.24-0.88; p = 0.0196)., Conclusions: Short-term DAPT after new-generation DES implantation may be more beneficial in elderly patients than in younger patients., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to examine whether stent length per patient and stent length per lesion are negative markers for 3-year outcomes in women following percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES)., Background: In the era of advanced stent technologies, whether stent length remains a correlate of adverse outcomes is unclear., Methods: Women treated with new-generation DES in 14 randomized trials from the WIN-DES (Women in Innovation and Drug-Eluting Stents) pooled database were evaluated. Total stent length per patient, which was available in 5,403 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 24 mm; quartile 3, 24 to 36 mm; quartile 4, ≥36 mm), and stent length per lesion, which was available in 5,232 women (quartile 1, 8 to 18 mm; quartile 2, 18 to 20 mm; quartile 3, 20 to 27 mm; quartile 4, ≥27 mm) were analyzed in quartiles. The primary endpoint was 3-year major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction, or target lesion revascularization., Results: In the per-patient analysis, a stepwise increase was observed with increasing stent length in the adjusted risk for 3-year MACE (p for trend <0.0001), myocardial infarction (p for trend <0.001), cardiac death (p for trend = 0.038), and target lesion revascularization (p for trend = 0.011) but not definite or probable stent thrombosis (p for trend = 0.673). In the per-lesion analysis, an increase was observed in the adjusted risk for 3-year MACE (p for trend = 0.002) and myocardial infarction (p for trend <0.0001) but not other individual endpoints. On landmark analysis for late event rates between 1 and 3 years, stent length per patient demonstrated weak associations with target lesion revascularization (p = 0.0131) and MACE (p = 0.0499), whereas stent length per lesion was not associated with higher risk for any late events, suggesting that risk was established early within the first year after PCI., Conclusions: In this pooled analysis of women undergoing PCI with new-generation DES, increasing stent length per patient and per lesion were independent predictors of 3-year MACE but were not associated with definite or probable stent thrombosis., (Copyright © 2018. Published by Elsevier Inc.)

Objective: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin has been reported to exert vasculo-protective action in diabetes. We investigated the vasculo-protective mechanism of atorvastatin by evaluating its effect on two major pathogenic molecules, FOXO1 and ICAM1, mediated by S-phase kinase-associated protein 2 (Skp2) in diabetic endothelial dysfunction. APPROACH AND RESULTS: [1] FOXO1: Hyperglycemic condition increased FOXO1 protein level in endothelial cells, which was reversed by atorvastatin. This atorvastatin effect was obliterated by treatment of protease inhibitor, suggesting that atorvastatin induces degradation of FOXO1. Immunoprecipitation showed that atorvastatin facilitated the binding of Skp2 to FOXO1, leading to ubiquitination and degradation of FOXO1. [2] ICAM-1: Increased ICAM1 in high glucose condition was reduced by atorvastatin. But this effect of atorvastatin was obliterated when Skp2 was inhibited, suggesting that atorvastatin enhances binding of Skp2 to ICAM1 leading to degradation. Actually, ubiquitination and degradation of ICAM-1 were reduced when Skp2 was inhibited. In vitro monocyte adhesion assay revealed that atorvastatin reduced monocyte adhesion on endothelial cells in high glucose condition, which was reversed by Skp2 knock-down., Conclusion: Atorvastatin strengthens Skp2 binding to FOXO1 or ICAM1, leading to ubiquitination and degradation. Skp2-dependent ubiquitination of major pathogenic molecules is the key mechanism for statin's protective effect on endothelial function in diabetes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate the effect of different body mass index (BMI) categories on clinical outcomes in female patients treated with percutaneous coronary intervention (PCI) and drug-eluting stents., Background: Patients with higher BMI might, paradoxically, have better long-term clinical outcomes after acute coronary syndrome treated with PCI., Methods: We pooled patient-level data for female participants from 26 randomized trials on PCI with drug-eluting stents. Patients were stratified into underweight (BMI, <18.5), normoweight (BMI, 18.5 to 24.9), overweight (BMI, 25 to 29.9), obese (BMI, 30 to 34.9), or morbidly obese (BMI, ≥35). The primary endpoint was major adverse cardiac events, a composite of death, myocardial infarction, or target lesion revascularization at 3 years., Results: Among 11,557 female patients included in the pooled database, 9,420 were treated with a drug-eluting stent and had BMI data available. Patients with higher BMI were significantly younger and with more cardiovascular risk factors. Only 139 patients were underweight and had significantly higher adjusted rates of cardiac mortality and all-cause mortality than the rest of the population (hazard ratio: 2.20 [1.31 to 3.71] compared with normoweight). There was a significantly lower frequency of unadjusted 3-year all-cause mortality in overweight, obese, and severely obese patients compared with normoweight. However, following multivariable analysis, a trend toward increased risk of death in severely obese patients was observed, describing an inverse "J"-shaped relation between BMI and 3-year mortality. Conversely, the relationship between BMI and other outcomes, such as major adverse cardiac events, was flat for normoweight and higher BMI., Conclusions: The risk of 3-year adjusted cardiac events did not differ across BMI groups, whereas the risk of all-cause mortality compared with normoweight was significantly higher in underweight patients and lower in overweight patients with a trend toward increased risk in the severely obese population., (Copyright © 2018. Published by Elsevier Inc.)

Background: Although there have been several reports that prasugrel can improve clinical outcomes, the efficacy and safety of prasugrel is unknown in Korean patients with acute myocardial infarction (AMI) undergoing successful revascularization., Methods: A total of 4421 patients [637 patients were prescribed prasugrel (60/10 or 5mg, loading/maintenance dose) and 3784 patients clopidogrel (600 or 300/75mg)] with AMI undergoing successful revascularization were enrolled from the core clinical cohort of Korea Acute Myocardial Infarction Registry-National Institute of Health., Results: After propensity score matching (637 pairs), there were no significant differences in baseline clinical and procedural characteristics and in-hospital medications between the two groups. The primary efficacy endpoint, defined as the composite of cardiac death, MI, stroke, or target vessel revascularization at 6 months showed no significant difference between prasugrel and clopidogrel (2.4% vs. 2.9%, p=0.593). Also, no difference was observed in the composite of cardiac death, MI, or stroke during hospitalization between two groups (0.8% vs. 0.9%, p=0.762). However, the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding was significantly higher in prasugrel compared with clopidogrel (5.3% vs. 2.7%, p=0.015). In multivariate linear regression analysis, trans-femoral intervention, use of glycoprotein IIb/IIIa inhibitors, use of calcium channel blocker, and use of prasugrel were independent predictors of in-hospital TIMI major or minor bleeding [odds ratio (OR)=6.918; 95% confidence interval (CI)=2.453-19.510, OR=2.577; 95% CI=1.406-4.724, OR=4.016; 95% CI=1.382-11.668, OR=2.022; 95% CI=1.101-3.714]., Conclusions: Our study shows that the recommended dose of prasugrel had significantly higher in-hospital bleeding complications without reducing ischemic events compared with clopidogrel. However, further large-scale, long-term, randomized clinical trials are required to accurately assess the efficacy and safety of prasgurel and to find out the optimal dose for Korean AMI patients., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Many patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are medically managed without coronary revascularization. The reasons vary and may impact prognosis., Methods: EPICOR Asia (NCT01361386) is a prospective study of hospital survivors post-ACS enrolled in 218 hospitals from 8 countries/regions in Asia (06/2011-05/2012). All medically managed NSTE-ACS patients were classified into 3 groups: 1) no coronary angiography (CAG-); 2) non-significant coronary artery disease (CAD) on angiogram (CAG+ CAD-); and 3) significant CAD (CAG+ CAD+). We compared baseline differences between patients medically managed and patients undergoing revascularization, and also between the medically managed groups. Adverse events were reported and compared up to 2years., Results: Of 6163 NSTE-ACS patients, 2272 (37%) were medically managed, with 1339 (59%), 254 (11%), and 679 (30%) in the CAG-, CAG+ CAD-, and CAG+ CAD+ groups, respectively. There were marked differences in the proportion of medically managed patients among the 8 countries/regions (13-81%). Medically managed patients had higher mortality at 2years compared with revascularization (8.7% vs. 3.0%, p<0.001). Among medically managed patients, CAG- patients were older, more likely to have pre-existing cardiovascular disease, and had the highest 2-year mortality (10.5% vs. 4.3% [CAG+ CAD-] and 6.6% [CAG+ CAD+], p<0.001). Mortality differences persisted after adjusting for other patient risk factors., Conclusions: Medically managed NSTE-ACS patients are a heterogeneous group with different risk stratification and variable prognosis. Identification of reasons underlying different management strategies, and key factors adversely influencing long-term prognosis, may improve outcomes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: The study sought to evaluate the presence of a clinically relevant rebound phenomenon after dual antiplatelet therapy (DAPT) discontinuation in randomized trials., Background: It is currently unknown whether clopidogrel discontinuation after short-term DAPT is associated with an early hazard of ischemic events., Methods: The authors performed an individual participant data analysis and aggregate meta-analysis. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of cardiac death, myocardial infarction (MI), or stroke., Results: The study included 11,473 PCI patients with individual participant data from 6 randomized trials comparing short-term DAPT (3 or 6 months) versus long-term DAPT (12 months or more). During the first 90 days following clopidogrel discontinuation, there was no significant increase in the risk of MACCE between patients randomized to short-term DAPT compared with long-term DAPT (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.71 to 1.98; p = 0.52; absolute risk difference 0.10%; 95% CI: -0.16% to 0.36%). The risk of MI or stent thrombosis was similar among patients randomized to short-term DAPT versus long-term DAPT (HR: 0.93; 95% CI: 0.46 to 1.90; p = 0.85). In the aggregate data meta-analysis of 11 trials including 38,919 patients, a higher risk of early MACCE was observed after long-term (≥12 months) DAPT duration (HR: 2.28; 95% CI: 1.69 to 3.09; p < 0.001) but not short-term (<12 months) DAPT duration (HR: 1.08; 95% CI: 0.67 to 1.74; p for interaction = 0.036)., Conclusions: Among patients undergoing PCI with predominantly new-generation DES, discontinuation of clopidogrel after 3 or 6 months DAPT duration was not associated with an early increase in adverse clinical events. An early increase in MACCE was observed after long-term (≥12 months) DAPT exposure., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Acute hyperglycemia on admission is common in acute myocardial infarction (AMI) patients regardless of diabetic status, and is known as one of prognostic factors. However, the effect of hyperglycemia on non-diabetic patients is still on debate., Methods: A total of 12,625 AMI patients (64.0±12.6years, 26.1% female) who were enrolled in Korea Acute Myocardial Infarction Registry-National Institute of Health between November 2011 and December 2015, were classified into 4367 diabetes (65.4±11.6years, 30.4% female) and 8228 non-diabetes (63.3±13years, 23.9% female). Patients were analyzed for in-hospital clinical outcome according to admission hyperglycemic status., Results: In diabetic patients, independent predictors of in-hospital mortality were old age, high HbA 1 C, pre-Thrombolysis In Myocardial Infarction (TIMI) flow 0, left ventricle ejection fraction<40%, cardiogenic shock and ventricular tachycardia. In non-diabetic patients, independent predictors of in-hospital mortality were old age, high admission glucose (≥200mg/dL), pre TIMI flow 0, failed percutaneous coronary intervention, low left ventricle ejection fraction<40%, cardiogenic shock, stent thrombosis and decreased Hb≥5g/dL. In hospital mortality was significantly higher in diabetic patients compared to non-diabetic patients (5.0% vs. 3.4%, p<0.001). However, non-diabetic patients with hyperglycemia have significantly higher mortality compared to diabetic patients (17.4% vs. 7.2%, p<0.001). Comorbidity including cardiogenic shock (p<0.001), cerebral hemorrhage (p=0.012), decreased Hb≥5g/dL (p=0.013), atrioventricular block (p<0.001) and ventricular tachycardia (p=0.007) was higher in non-diabetic with hyperglycemia than in diabetic patients., Conclusions: These findings underscore clinical significance of admission hyperglycemia on in-hospital mortality in non-diabetic AMI patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y 12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose., Methods: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk., Findings: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61-0·85) in the derivation cohort, and 0·70 (0·65-0·74) in the PLATO trial validation cohort and 0·66 (0·61-0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (p interaction =0·007), and exerted a significant ischaemic benefit only in this latter group., Interpretation: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration., Funding: None., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Studies comparing the drug-eluting balloon (DEB) with contemporary drug-eluting stent (DES) in the treatment of in-stent restenosis (ISR) have been scarce. We compared that the efficacy and safety of contemporary DES versus DEB in unselected, real world patients of ISR occurred in bare-metal stent or DES., Methods: Patient-level pooled analysis from nationwide multicenter registries was performed with 628 consecutive patients who underwent ISR treatment using 2nd or 3rd generation DES or DEB. Target lesion failure (TLF) and patient-oriented composite outcomes (POCO, composite of all-cause mortality, all-cause myocardial infarction, or any revascularization) at 1-year follow-up were compared between the DES and DEB groups., Results: A total of 628 patients with 697 ISR lesions were treated using newer generation DES (n=409) or DEB (n=219). About 55.1% presented with acute coronary syndrome, and 15.1% showed left ventricular dysfunction. The risks of TLF and POCO were significantly lower in the DES group, even after being adjusted by an inverse probability weighted model (TLF, 9.2% vs. 17.9%, HR adjust 0.22, 95% CI 0.11-0.47; POCO, 12.4% vs. 24.1%, HR adjust 0.25, 95% CI 0.13-0.48, all p-values<0.001), mainly driven by the significantly lower risk of target lesion revascularization (TLR) (7.6% vs. 13.0%, HR adjust 0.21, 95% CI 0.09-0.49, p<0.001). Treatment of ISR with DEB independently predicted TLF (HR 1.87, 95% CI 1.05-3.02, p=0.034) along with multi-vessel disease, chronic kidney disease, type B2 or C lesion, and number of treated lesion>1., Conclusions: In unselected patients of ISR, clinical outcome at one year was mainly dependent on difference in TLR and found to be better with contemporary DES than DEB., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)