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Background: The contribution of sex as an independent risk factor for cardiovascular disease still remains controversial. The present study investigated the impact of sex on long-term clinical outcomes in Korean acute myocardial infarction (AMI) patients with a history of current smoking on admission after drug-eluting stents (DESs). Methods: A total of 12,565 AMI patients (male: n = 11767 vs. female: n = 798) were enrolled. Major adverse cardiac events (MACEs) comprising all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcomes that were compared between the two groups. Probable or definite stent thrombosis (ST) was the secondary outcome. Results: After adjustment, the early (30 days) cumulative incidences of MACEs (adjusted hazard ratio [aHR]: 1.457; 95% confidence interval [CI]: 1.021–2.216; p = 0.035) and all-cause death (aHR: 1.699; 95% CI: 1.074–2.687; p = 0.023) were significantly higher in the female group than in the male group. At 2 years, the cumulative incidences of all-cause death (aHR: 1.561; 95% CI: 1.103–2.210; p = 0.012) and Re-MI (aHR: 1.880; 95% CI: 1.089–2.974; p = 0.022) were significantly higher in the female group than in the male group. However, the cumulative incidences of ST were similar between the two groups (aHR: 1.207; 95% CI: 0.583–2.497; p = 0.613). Conclusions: The female group showed worse short-term and long-term clinical outcomes compared with the male group comprised of Korean AMI patients with a history of current smoking after successful DES implantation. However, further studies are required to confirm these results.

Because of paucity of published data, we evaluated the 2-year major clinical outcomes between early invasive (EI) and delayed invasive (DI) strategies according to the stage of chronic kidney disease (CKD) in patients with non-ST-segment elevation myocardial infarction (NSTEMI), who underwent a successful newer-generation drug-eluting stent (DES) implantation.A total of 8241 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry (KAMIR). Based on baseline estimated glomerular filtration rate (eGFR; ≥90, 60-89, 30-59, and30 mL/min/1.73 mAfter multivariable-adjusted and propensity score-adjusted analyses, the cumulative incidence of MACE (group A, p = 0.139 and p = 0.103, respectively; group B, p = 0.968 and p = 0.608, respectively; group C, p = 0.111 and p = 0.196, respectively; group D, p = 0.882 and p = 0.571, respectively), all-cause death, re-MI, and any repeat revascularization was similar between the EI and DI groups in the 4 different renal function groups.In the era of newer-generation DES, EI and DI strategies showed comparable major clinical outcomes in patients with NSTEMI and CKD during a 2-year follow-up period. However, to confirm these results, further randomized, large-scale, long-term follow-up studies are needed.

Background/aims Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Objectives The purpose of this study was to test whether the success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) increased with pre-procedural coronary computed tomography angiography (CTA). Background Coronary CTA provides valuable information before and during CTO-PCI. However, there are no randomized data that explore whether coronary CTA increases its success rate. Methods In this multicenter, randomized trial, a total of 400 patients with CTO were randomized to receive PCI with pre-procedural coronary CTA (coronary CTA–guided group; n = 200) or without coronary CTA (angiography-guided group; n = 200) between January 2014 and September 2019. The primary endpoint was the successful recanalization rate, a final TIMI (Thrombolysis In Myocardial Infarction) grade ≥2, and ≤30% residual stenosis on the final angiogram. Results A total of 10 operators performed PCI. Successful recanalization was achieved in 187 patients (93.5%) in the coronary CTA–guided group and in 168 patients (84.0%) in the angiography-guided group (absolute difference, 9.5% [95% confidence interval: 3.4% to 15.6%]; p = 0.003). When comparing the success rates according to the Multicenter CTO Registry of Japan score (J-CTO), the coronary CTA guidance was favored over the angiography-guidance in the subset of J-CTO ≥2 versus in the subset of J-CTO Conclusions Pre-procedural coronary CTA-guidance for CTO resulted in higher success rates with numerically fewer immediate periprocedural complications such as coronary perforations or periprocedural myocardial infarction than angiography guidance. Higher success rates were more prominently observed in patients with CTO who had a high J-CTO score than those who did not. (Role of CT Scan for the Successful Recanalization of Chronic Total Occlusion; a Randomized Comparison Between 3D CT-guided PCI vs. Conventional Treatment [CT-CTO Trial]; NCT02037698 )

Objectives The aim of this study was to determine whether 1 month of dual-antiplatelet therapy (DAPT) followed by aspirin monotherapy after polymer-free drug-coated stent (PF-DCS) implantation is noninferior to 6 to 12 months of DAPT after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Background It is necessary to determine the optimal minimal duration of DAPT followed by aspirin monotherapy after percutaneous coronary intervention (PCI). Methods In this trial, 3,020 patients with coronary artery disease considered for PCI for noncomplex lesions were randomized to 1-month DAPT after PF-DCS (n = 1,507) or 6- to 12-month DAPT after BP-DES (n = 1,513). The primary endpoint was the 1-year composite of cardiac death, nonfatal myocardial infarction, target vessel revascularization, stroke, or major bleeding (noninferiority hypothesis margin of 3%). Results The primary endpoint occurred in 88 patients (5.9%) in the 1-month DAPT after PF-DCS group and 98 patients (6.5%) in the 6- to 12-month DAPT after BP-DES group (absolute difference −0.7%; upper limit of 1-sided 97.5% confidence interval: 1.33%; P Conclusions Among patients who underwent PCI for noncomplex lesions, 1-month DAPT followed by aspirin monotherapy after PF-DCS implantation was noninferior to 6- to 12-month DAPT after BP-DES implantation for the 1-year composite of cardiovascular events or major bleeding. The present findings need to be interpreted in the setting of different types of stents according to antiplatelet strategy. (A Randomized Controlled Comparison Between One Versus More Than Six Months of Dual Antiplatelet Therapy After Biolimus A9-Eluting Stent Implantation; NCT02513810 )

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.

We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02494895.

The 2-year clinical outcomes according to pre-percutaneous coronary intervention (PCI) thrombolysis in myocardial infarction (TIMI) flow grade and reperfusion timing were investigated in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who received newer-generation drug-eluting stents. A total of 7506 NSTEMI patients were divided into 2 groups: early (PCI ≤ 24 hours: n = 6398; pre-PCI TIMI 0/1 [n = 2729], pre-PCI TIMI 2/3 [n = 3669]) and delayed (PCI > 24 hours: n = 1108; pre-PCI TIMI 0/1 [n = 428], pre-PCI TIMI 2/3 [n = 680]) invasive groups. Major adverse cardiac events were defined as all-cause death, recurrent myocardial infarction, or any repeat revascularization. All-cause death ( P = 0.005 and 0.009, respectively) and cardiac death ( P = .003 and 0.046, respectively) were significantly higher in pre-PCI TIMI 0/1 patients than in pre-PCI TIMI 2/3 patients both in the early and delayed invasive groups. In pre-PCI TIMI 0/1 patients, all-cause death rate was significantly higher in the delayed group ( P = .023). In pre-PCI TIMI 2/3 patients, the clinical end point was similar between the 2 groups. An early invasive strategy is preferred to a delayed invasive strategy in reducing all-cause death in patients with pre-PCI TIMI 0/1. However, in patients with pre-PCI TIMI 2/3, both treatment strategies are acceptable.

Objective The comparative long-term clinical outcomes between patients with prediabetes and diabetes in patients with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) who were undergoing percutaneous coronary intervention (PCI) are not well known. We therefore compared the 2-year clinical outcomes in such patients. Methods A total of 2963 patients with NSTEMI and MVD [normoglycemia (group A, n = 629), prediabetes (group B, n = 802), and diabetes (group C, n = 1532)] were evaluated. The primary outcomes were the occurrence of major adverse cardiac events (MACE) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization. The secondary outcome was stent thrombosis. Results The cumulative incidence of MACE as well as for death or MI in group B and C were similar when compared to each other. However, they (P = 0.048 and P = 0.017, respectively and P = 0.022 and P = 0.001, respectively) were significantly higher than in group A. The cumulative incidence of all-cause death in group B (P = 0.042) and all-cause death and cardiac death in group C (P = 0.001 and P = 0.028, respectively) were significantly higher than in group A. However, those of all-cause death, cardiac death, Re-MI, any repeat revascularization, and ST were not significantly different between groups B and C. Conclusion In this study, patients with NSTEMI and MVD who underwent successful implantation of newer-generation DES and were prediabetic had worse outcomes compared to normoglycemics and comparable to those with diabetes.

Objectives The aim of this study was to assess whether the effects of ticagrelor monotherapy after 3-month dual-antiplatelet therapy (DAPT) are consistent among patients presenting with ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction, and unstable angina treated with drug-eluting stents. Background Ticagrelor monotherapy after short-term DAPT has not been investigated in patients with STEMI. Methods This was a pre-specified, stratified, subgroup analysis of the STEMI cohort from the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome) trial, which constituted 36% of the total population. The primary outcome was a composite of major bleeding and major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, stent thrombosis, stroke, or target vessel revascularization). The secondary outcomes were major bleeding and MACCE. Results The incidence of the primary outcome was 4.4% in patients with STEMI (n = 1,103), 6.0% in those with non–ST-segment elevation myocardial infarction (n = 1,027), and 4.1% in those with unstable angina (n = 926), without statistical significance (p = 0.09). Compared with ticagrelor-based 12-month DAPT, ticagrelor monotherapy after 3-month DAPT showed consistent effects on the primary outcome across clinical presentations (p for interaction [pint] = 0.64). Furthermore, the effect of ticagrelor monotherapy on the reduction of major bleeding was consistent across clinical presentations (pint = 0.36). The effect of ticagrelor monotherapy on MACCE was also consistent in patients with STEMI, without evidence of a higher risk for MACCE (pint = 0.14). Conclusions This pre-specified subgroup analysis revealed no heterogeneity in the effects of ticagrelor monotherapy after 3-month DAPT, compared with 12-month DAPT, for the primary outcome, major bleeding, and MACCE across clinical presentations including STEMI, though larger studies are needed to demonstrate these findings with adequate power. (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome [TICO Study]; NCT02494895 )

Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08–5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding.Trial registration: NCT02707445 (https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1).

Hyperglycemia is an important risk factor for poor clinical outcomes in patients with acute myocardial infarction (AMI). The relative superiority of the long-term clinical outcomes of durable-polymer (DP) -based and biodegradable-polymer (BP) -based newer-generation drug-eluting stents (DESs) after successful percutaneous coronary intervention (PCI) in patients with AMI and prediabetes is not well established. We compared the clinical outcomes in such patients between DP-based and BP-based newer-generation DESs.A total of 4,377 patients with AMI and prediabetes were divided into the following two groups: the DP-DES group (n = 3,775; zotarolimus-eluting stents [ZES; n = 1,546] and everolimus-eluting stents [EES; n = 2,229]) and the BP-DES group (n = 602; biolimus-eluting stents [BES]). The primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as all-cause death, recurrent myocardial infarction (re-MI), or any repeat revascularization. The secondary endpoint was the occurrence of stent thrombosis (ST).The 2-year adjusted hazard ratio (aHR) of MACEs for ZES versus EES, ZES versus BES, EES versus BES, and ZES/EES versus BES (aHR: 1.125; 95% confidence interval [CI], 0.834-1.518; P = 0.440) were similar. The cumulative incidence of ST was also comparable between the DP-DES and BP-DES groups (aHR: 1.407; 95% CI, 0.476-4.158; P = 0.537). Moreover, the 2-year aHRs of all-cause death, CD, re-MI, target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR were similar.Patients with AMI and prediabetes who received DP-DES or BP-DES during PCI showed comparable safety and efficacy during the 2-year follow-up period.

Background and aims The long-term comparative results between culprit-only percutaneous coronary intervention (C–PCI) and multivessel PCI (M-PCI) or those between complete revascularization (CR) and incomplete revascularization (IR) in patients with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) after successful newer-generation drug-eluting stent (DES) implantation are limited. Therefore, we compared the 2-year clinical outcomes in such patients. Methods A total of 4588 patients with NSTEMI and MVD (C–PCI, n = 2055; M-PCI, n = 2533; CR, n = 2029; IR, n = 504) were evaluated. The primary outcome was major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction MI, and any repeat coronary revascularization. The secondary outcome was stent thrombosis (ST). Results The cumulative incidences of the primary and secondary outcomes were similar in the three comparison groups (C–PCI vs. M-PCI, CR vs. IR, or CR vs. C–PCI). However, the cumulative incidence of non-target vessel revascularization (non-TVR) was higher in the C–PCI group than in the M-PCI group (adjusted hazard ratio [aHR]: 2.011; 95% confidence interval [CI]: 1.942–3.985; p = 0.012), higher in the IR group than in the CR group (aHR: 2.051; 95% CI: 1.216–4.183; p = 0.043), and higher in the C–PCI group than in the CR group (aHR: 2.099; 95% CI: 1.237–3.564; p = 0.006). Conclusions Regarding the higher cumulative incidence of non-TVR, M-PCI and CR were preferred compared to C–PCI or IR in patients with NSTEMI and MVD. However, further randomized studies are required to confirm these findings.

Obesity is a medical condition in which excess body fat has accumulated to a serious extent. It is a chronic disease that can lead to dyslipidemia, insulin resistance, and type 2 diabetes. In the present study, we investigated the anti-obesity effects of Sicyos angulatus (SA) extract on a high-fat diet (HFD)-induced C57BL/6J obese mice. The mice were divided into vehicle and three SA groups (25, 50, and 100 mg/kg body weight). The mice were fed a HFD with or without SA for 12 weeks. The oral administration of SA reduced body and adipose tissue weight in HFD-fed mice compared to those in the vehicle group (p

Background Intensive statin therapy reduces cardiovascular events in acute coronary syndrome. The data concerning the long-term clinical impacts of statin therapy between ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) after drug-eluting stent implantation are limited. We compared the 2-year clinical outcomes between these 2 groups after statin therapy. Materials and Methods A total of 30,616 Korean patients with acute myocardial infarction (AMI) were enrolled. Among them, 13,686 patients were classified as group A (STEMI statin user), 3,824 patients were as group B (STEMI statin nonuser), 10,398 patients were as group C (NSTEMI statin user), and 2,708 patients were as group D (NSTEMI statin nonuser). The major clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, recurrent myocardial infarction (re-MI), and any repeat revascularization during a 2-year follow-up period. Results After adjustment, the cumulative risks of MACE (adjusted hazard ratio [aHR] = 1.112 [1.002-1.235]; P = 0.047), all-cause death (aHR = 1.271 [1.054-1.532]; P = 0.012), and target vessel revascularization (TVR, aHR = 1.262 [1.049-1.518]; P = 0.014) in group C were significantly higher than group A. The cumulative risks of MACE, all-cause death, and cardiac death of the statin nonuser group (groups B and D) were significantly higher compared with statin user group (groups A and C). Conclusions Statin therapy was more effective in reducing the cumulative risks of MACE, all-cause death, and TVR in the STEMI group than NSTEMI group in Korean patients with AMI after successful drug-eluting stent implantation.

Chronic alcohol feeding increases the levels of 2-arachidonoylglycerol (2-AG) in the liver, which activates hepatic cannabinoid receptor type 1 (CB1R), leading to oxidative liver injury. 2-AG biosynthesis is catalyzed by diacylglycerol lipase (DAGL). However, the mechanisms regulating hepatic DAGL gene expression and 2-AG production are largely unknown. In this study, we show that CB1R-induced estrogen-related receptor γ (ERRγ) controls hepatic DAGL gene expression and 2-AG levels. Arachidonyl-2'-chloroethylamide (ACEA), a synthetic CB1R agonist, significantly upregulated ERRγ, DAGLα, and DAGLβ, and increased 2-AG levels in the liver (10 mg/kg) and hepatocytes (10 μM) of wild-type (WT) mice. ERRγ overexpression upregulated DAGLα and DAGLβ expressions and increased 2-AG levels, whereas ERRγ knockdown abolished ACEA-induced DAGLα, DAGLβ, and 2-AG in vitro and in vivo. Promoter assays showed that ERRγ positively regulated DAGLα and DAGLβ transcription by binding to the ERR response element in the DAGLα and DAGLβ promoters. Chronic alcohol feeding (27.5% of total calories) induced hepatic steatosis and upregulated ERRγ, leading to increased DAGLα, DAGLβ, or 2-AG in WT mice, whereas these alcohol-induced effects did not occur in hepatocyte-specific CB1R knockout mice or in those treated with the ERRγ inverse agonist GSK5182 (40 mg/kg in mice and 10 μM in vitro). Taken together, these results indicate that suppression of alcohol-induced DAGLα and DAGLβ gene expressions and 2-AG levels by an ERRγ-specific inverse agonist may be a novel and attractive therapeutic approach for the treatment of alcoholic liver disease.

Objectives The goal of this study was to evaluate whether the beneficial effect of use of intravascular ultrasound (IVUS) is sustained for long-term follow-up. Background The use of IVUS promoted favorable 1-year clinical outcome in the IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) trial. It is not known, however, whether this effect is sustained for long-term follow-up. Methods The IVUS-XPL trial randomized 1,400 patients with long coronary lesions (implanted stent length ≥28 mm) to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. Five-year clinical outcomes were investigated in patients who completed the original trial. The primary outcome was the composite of major adverse cardiac events, including cardiac death, target lesion–related myocardial infarction, or ischemia-driven target lesion revascularization at 5 years, analyzed by intention-to-treat. Results Five-year follow-up was completed in 1,183 patients (85%). Major adverse cardiac events at 5 years occurred in 36 patients (5.6%) receiving IVUS guidance and in 70 patients (10.7%) receiving angiographic guidance (hazard ratio: 0.50; 95% confidence interval: 0.34 to 0.75; p = 0.001). The difference was driven mainly by a lower risk for target lesion revascularization (31 [4.8%] vs. 55 [8.4%]; hazard ratio: 0.54; 95% confidence interval: 0.33 to 0.89; p = 0.007). By landmark analysis, major adverse cardiac events between 1 and 5 years occurred in 17 patients (2.8%) receiving IVUS guidance and in 31 patients (5.2%) receiving angiographic guidance (hazard ratio: 0.53; 95% confidence interval: 0.29 to 0.95; p = 0.031). Conclusions Compared with angiography-guided stent implantation, IVUS-guided stent implantation resulted in a significantly lower rate of major adverse cardiac events up to 5 years. Sustained 5-year clinical benefits resulted from both within 1 year and from 1 to 5 years post-implantation. (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions [IVUS-XPL Study]: Retrospective and Prospective Follow-Up Study; NCT03866486)

Objectives Portal vein thrombosis is not uncommon in liver cirrhosis patients. Previously, portal vein throm-bosis had been considered as a contraindication to liver transplant because of technical challenges for adequate restoration of portal inflow followed by high morbidity and mortality. However, alternative options for portal vein thrombosis during liver transplant have been introduced, and portal vein thrombosis is now no longer considered as an absolute contraindication for liver transplant. Herein, we introduce our ex-periences and outcomes of liver transplant for patients with portal vein thrombosis. Materials and methods Between March 2014 and June 2018, 65 patients underwent liver transplant at our institution, with 13 (20%) having portal vein thrombosis preoperatively. The characteristics and management of these patients were reviewed retrospectively, and outcomes were compared with those of patients without portal vein thrombosis. Results The type of portal vein thrombosis included Yerdel grade 1 in 7 patients (53.8%), grade 2 in 4 patients (30.8%), grade 3 in 1 patient (7.7%), and grade 4 in 1 patient (7.7%). For restoration of portal inflow, eversion thrombectomy was performed in 11 patients (84.6%), renoportal bypass in 1 patient (7.7%) with grade 4 portal vein thrombosis, and superior mesenteric vein jump graft in 1 patient (7.7%) with grade 2 portal vein thrombosis. There was no portal vein-related morbidity except for 1 patient who needed portal vein stent because of stricture. Outcomes after liver transplant were comparable among patients with and without portal vein thrombosis. Conclusions Although the surgical procedure has a technical complexity, liver transplant is no longer a contraindication for patients with portal vein thrombosis because of various alternative options, allowing similar outcomes among patients with and without portal vein thrombosis.

Because available data are limited, we compared the 2-year clinical outcomes among different reperfusion strategies (culprit-only percutaneous coronary intervention (C-PCI), multivessel PCI (M-PCI), complete revascularization (CR) and incomplete revascularization (IR)) of multivessel disease (MVD) undergoing newer-generation drug-eluting stent implantation in patients with non-ST-elevation myocardial infarction (NSTEMI) and chronic kidney disease (CKD). In this nonrandomized, multicenter, retrospective cohort study, a total of 1042 patients (C-PCI, n = 470, M-PCI, n = 572, CR, n = 432, IR, n = 140) were recruited from the Korea Acute Myocardial Infarction Registry (KAMIR) and evaluated. The primary outcome was the occurrence of major adverse cardiac events, defined as all-cause death, recurrent myocardial infarction and any repeat coronary revascularization. The secondary outcome was probable or definite stent thrombosis. During the 2-year follow-up period, the cumulative incidences of the primary (C-PCI vs. M-PCI, adjusted hazard ratio (aHR), 1.020, p = 0.924, CR vs. IR, aHR, 1.012, p = 0.967, C-PCI vs. CR, aHR, 1.042, p = 0.863, or C-PCI vs. IR, aHR, 1.060, p = 0.844) and secondary outcomes were statistically insignificant in the four comparison groups. In the contemporary newer-generation DES era, C-PCI may be a better reperfusion option for patients with NSTEMI with MVD and CKD rather than M-PCI, including CR and IR, with regard to the procedure time and the risk of contrast-induced nephropathy. However, further well-designed, large-scale randomized studies are warranted to confirm these results.

Background: Because limited data are available, the present study investigated 2-year major clinical outcomes after angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) therapy in patients with acute myocardial infarction (AMI) and prediabetes after successful implantation of newer-generation drug-eluting stents (DESs). Methods: Overall, 2932 patients with AMI and prediabetes were classified into two groups — the ACEIs group (n = 2059) and the ARBs group (n = 873). The primary endpoint was the occurrence of patient-oriented composite outcome (POCO), defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat revascularization. The secondary endpoint was definite or probable stent thrombosis (ST). Results: The cumulative incidences of POCO (adjusted hazard ratio [aHR]: 1.020; 95% confidence interval [CI]: 0.740–1.404; p = 0.906), all-cause death (aHR: 1.394; 95% CI: 0.803–2.419; p = 0.238), Re-MI (aHR: 1.210; 95% CI: 0.626–2.340; p = 0.570), any repeat revascularization (aHR: 1.150; 95% CI: 0.713–1.855; p = 0.568), and ST (aHR: 1.736; 95% CI: 0.445–6.766; p = 0.427) were similar between the groups. These results were confirmed after propensity score-adjusted analysis. Conclusions: In this study, patients with AMI and prediabetes who received ACEIs or ARBs showed comparable clinical outcomes during the 2-year follow-up period.

Although liquid biopsy of blood is useful for cancer diagnosis and prediction of prognosis, diagnostic and prognostic value of ctDNA in bile fluid for BTCs are not clear yet. To determine whether liquid biopsy for circulating tumor DNA (ctDNA) can replace tissue biopsy when assessing somatic mutations in biliary tract cancers (BTCs). Bile samples were obtained from 42 patients with BTC. Matched formalin-fixed paraffin-embedded (FFPE) samples were obtained from 20 of these patients and matched plasma samples from 16 of them. Droplet digital PCR (ddPCR) was used for detection KRAS somatic mutation. KRAS mutations were identified in the bile ctDNA of 20 of 42 (48%) patients. Patients with mutant KRAS showed significantly worse survival than those with wild-type KRAS (2-year survival rates: 0% vs. 55.5%, respectively, p = 0.018). There was 80.0% mutational concordance between the paired bile ctDNA and FFPE samples, and 42.9% between the plasma and FFPE samples. On transcriptomic sequencing of one set of paired bile and FFPE samples, expression level of KRAS-associated signaling oncogenes in the bile and tissue samples showed a strong positive correlation (r = 0.991, p &lt, 0.001). Liquid biopsy of bile reliably detect mutational variants within the bile ctDNA of BTC patients. These results suggest that bile is an effective biopsy fluid for ctDNA analysis.

We investigated the 2-year efficacy of statin treatment according to baseline renal function in patients with acute myocardial infarction (AMI) not requiring dialysis undergoing newer-generation drug-eluting stent (DES) implantation. A total of 18,875 AMI patients were classified into group A (statin users, n = 16,055) and group B (statin nonusers, n = 2820). According to the baseline estimated glomerular filtration rate (eGFR, ≥90, 60–89, 30–59 and &lt, 30 mL/min/1.73 m2), these two groups were sub-classified into groups A1, A2, A3 and A4 and groups B1, B2, B3 and B4. The major adverse cardiac events (MACE), defined as all-cause death, recurrent MI (re-MI) and any repeat revascularization, were evaluated. The MACE (group A1 vs. B1, p = 0.002, group A2 vs. B2, p = 0.007, group A3 vs. B3, p &lt, 0.001, group A4 vs. B4, p &lt, 0.001), all-cause death (p = 0.006, p &lt, 0.001, p &lt, 0.001, respectively) and cardiac death (p = 0.004, p &lt, 0.001, respectively) rates were significantly higher in statin nonusers than those in statin users. Despite the beneficial effects of statin treatment, the MACE (group A1 vs. A2 vs. A3 vs. A4: 5.2%, 6.4%, 10.1% and 18.5%, respectively), all-cause mortality (0.9%, 1.8%, 4.6% and 12.9%, respectively) and cardiac death (0.4%, 1.0%, 2.6% and 6.8%, respectively) rates were significantly increased as eGFR decreased in group A. These results may be related to the peculiar characteristics of chronic kidney disease, including increased vascular calcification and traditional or nontraditional cardiovascular risk factors. In the era of newer-generation DESs, although statin treatment was effective in reducing mortality, this beneficial effect was diminished in accordance with the deterioration of baseline renal function.

Background Comparative studies regarding the long-term clinical outcomes of statin intensity between acute myocardial infarction (AMI) patients with prediabetes and those with type 2 diabetes mellitus (T2DM), after successful implantation of newer-generation drug-eluting stents (DES) with statin treatment, are limited. We compared the 2-year clinical outcomes between these patients. Methods A total of 11,612 AMI patients were classified as statin users (n = 9893) and non-users (n = 1719). Thereafter, statin users were further divided into high-intensity (n = 2984) or low-moderate-intensity statin (n = 6909) treatment groups. Those in these two groups were further classified into patients with normoglycemia, prediabetes, and T2DM. The major outcomes were the occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat coronary revascularization. Results After adjusting for both high-intensity and low-moderate-intensity statin users, the cumulative incidences of MACE (p = 0.737, p = 0.062, respectively), all-cause death, Re-MI, and any repeat revascularization were similar between the prediabetes and T2DM groups. In the total study population, both high-intensity and low-moderate-intensity statin treatments showed comparable results. However, in the patients who enrolled after October 2012, the cumulative incidences of MACE (aHR 1.533; 95% CI 1.144–2.053; p = 0.004) and any repeat revascularization (aHR, 1.587; 95% CI 1.026–2.456; p = 0.038) were significantly lower in high-intensity statin users than in low-moderate intensity statin users. The beneficial effects of high-intensity compared to low-moderate-intensity statin therapy were more apparent in the normoglycemia group than hyperglycemia group, as it reduced the cumulative incidences of MACE (aHR 1.903; 95% CI 1.203–3.010; p = 0.006) and any repeat revascularization (aHR 3.248; 95% CI 1.539–6.854; p = 0.002). Conclusions In this retrospective registry study, prediabetes and T2DM groups showed comparable clinical outcomes, after administering both high-intensity and low-moderate-intensity statin treatments. However, these results are likely to be clearly proved by further studies, especially in patients with AMI who are being treated in contemporary practice. Trial registration Retrospectively registered.

Hypertension and diabetes mellitus (DM) are major risk factors for the cardiovascular disease. In this retrospective cohort study, we compared the long-term clinical outcomes between antecedent hypertension and DM in acute myocardial infarction (AMI) patients after stent implantation.A total of 32 938 eligible AMI patients were enrolled and divided into the four groups according to the presence or absence of hypertension and DM (hypertension -/DM -[group A, 13 773 patients], hypertension +/DM -[group B, 10 395 patients], hypertension -/DM + [group C, 3050 patients], and hypertension +/DM + [group D, 5720 patients]). The clinical endpoint was the cumulative incidence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (Re-MI) and any repeat revascularization during the 2-year follow-up period.After adjustment, the cumulative incidence of MACEs (adjusted hazard ratio [aHR], 1.232; 95% confidence interval [CI], 0.982-1.567; P = .071), all-cause death, and e-MI Re-MI were similar between the group B and C. However, the cumulative incidences of any repeat revascularization (aHR, 1.438; 95% CI, 1.062-1.997; P = .007), target lesion revascularization (TLR) (aHR, 2.467; 95% CI, 1.552-3.922; P .001), and target vessel revascularization (TVR) (aHR, 1.671; 95% CI, 1.256-2.222; P .001) were significantly higher in group C compared with group B.This large number of a nonrandomized and multicenter cohort study clearly demonstrated the detrimental impacts of the hypertension and diabetes on long-term clinical outcomes. Moreover, higher incidence of repeat revascularization after PCI in diabetic AMI patients a major concern until recently.背景: 高血压和糖尿病(diabetes mellitus, DM)是心血管疾病的主要危险因素。在这项回顾性队列研究中, 我们比较了高血压和DM患者在因急性心肌梗死(acute myocardial infarction, AMI)接受支架置入术后的长期临床结局。 方法: 共入选了32 938名符合条件的AMI患者, 根据有无高血压和DM分为4组(高血压−/DM−[A组, 13 773例患者]；高血压+/DM−[B组, 10 395例患者]；高血压−/DM+[C组, 3050例患者]；以及高血压+/DM+[D组, 5720例患者])。临床终点为2年随访期间的主要不良心血管事件[MACEs, 定义全因死亡、复发性心肌梗死(Re-MI)和任何再次血运重建术]的累计发生率。 结果: 经过校正后, 发现B组C组之间的MACEs(校正后风险比[aHR], 1.232；95%置信区间[CI], 0.982-1.567；P=0.071)、全因死亡和e-MI Re-MI的累积发生率均相似。然而, 与B组相比, C组的任何再次血运重建术(aHR, 1.438；95% CI, 1.062-1.997；P=0.007)、靶病变血运重建术(target lesion revascularization, TLR)(aHR, 2.467；95% CI, 1.552-3.922；P0.001)以及靶血管血运重建术(target vessel revascularization, TVR)(aHR, 1.671；95% CI, 1.256-2.222；P0.001)的累积发生率均显著更高。 结论: 这项大型的非随机、多中心队列研究明确显示了高血压和糖尿病对长期临床结局的不利影响。此外, 糖尿病AMI患者接受PCI术后需要再次血运重建术的可能性更高, 这一点直到最近才引起关注。.

Dyslipidemia-induced atherosclerosis, which has a risk of high morbidity and mortality, can be alleviated by metabolic activation associated with mitochondrial function. The effect of dichloroacetate (DCA), a general pyruvate dehydrogenase kinase (PDK) inhibitor, on in vivo energy expenditure in ApoE−/− mice fed a western diet (WD) has not yet been investigated. WD-fed ApoE−/− mice developed atherosclerotic plaques and hyperlipidemia along with obesity, which were significantly ameliorated by DCA administration. Increased oxygen consumption was associated with heat production in the DCA-treated group, with no change in food intake or physical activity compared with those of the control. These processes were correlated with the increased gene expression of Dio2 and Ucp-1, which represents brown adipose tissue (BAT) activation, in both WD-induced atherosclerosis and high-fat-induced obesity models. In addition, we found that DCA stimulated hepatic fibroblast growth factor 21 (Fgf21) mRNA expression, which might be important for lowering lipid levels and insulin sensitization via BAT activation, in a dose- and time-dependent manner associated with serum FGF21 levels. Interestingly, Fgf21 mRNA expression was mediated in an AMP-activated protein kinase (AMPK)-dependent manner within several minutes after DCA treatment independent of peroxisome proliferator-activated receptor alpha (PPARα). Taken together, the results suggest that enhanced glucose oxidation by DCA protects against atherosclerosis by inducing hepatic FGF21 expression and BAT activation, resulting in augmented energy expenditure for heat generation., Atherosclerosis: Expending surplus energy on cardiovascular health A compound that shifts cellular energy consumption into inflation confers effective protection against cardiovascular diseases. Elevated lipid put people at risk of atherosclerosis and coronary artery disease, but new findings from researchers led by In-Kyu Lee at Kyungpook National University in Daegu, South Korea reveal a potential strategy for preventing such accumulation. They have demonstrated that a small molecule called dichloroacetate targeting for mitochondrial respiration boosts metabolic activity and impedes atherosclerosis progression in a experimental animal model fed Western diets. Dichloroacetate might work by stimulating signals that activate brown adipose tissue, a type of fat that burns excess nutrients for energy rather than storing them. These signaling pathways have been linked to other aspects of obesity and cardiovascular disease, suggesting dichloroacetate may be a promising drug candidate.

Although molecular characterization of iCCA has been studied recently, integrative analysis of molecular and clinical characterization has not been fully established. If molecular features of iCCA can be predicted based on clinical findings, we can approach to distinguish targeted treatment. We analyzed RNA sequencing data annotated with clinicopathologic data to clarify molecular-specific clinical features and to evaluate potential therapies for molecular subtypes. We performed next-generation RNA sequencing of 30 surgically resected iCCA from Korean patients and the clinicopathologic features were analyzed. The RNA sequences from 32 iCCA resected from US patients were used for validation. Patients were grouped into two subclasses on the basis of unsupervised clustering, which showed a difference in 5-year survival rates (48.5% vs 14.2%, p = 0.007) and similar survival outcome in the US samples. In subclass B (poor prognosis), both data sets were similar in higher carcinoembryonic antigen and cancer antigen 19-9 levels, underlying cholangitis, and bile duct-type pathology; in subclass A (better prognosis), there was more frequent viral hepatitis and cholangiolar-type pathology. On pathway analysis, subclass A had enriched liver-related signatures. Subclass B had enriched inflammation-related and TP53 pathways, with more frequent KRAS mutations. CCA cell lines with similar gene expression patterns of subclass A were sensitive to gemcitabine. Two molecular subtypes of iCCA with distinct clinicopathological differences were identified. Knowledge of clinical and pathologic characteristics can predict molecular subtypes, and knowledge of different subtype signaling pathways may lead to more rational, targeted approaches to treatment.

Background and aims There are limited data comparing clinical outcomes among new-generation drug-eluting stents (DES) in ST-segment elevation myocardial infarction (STEMI) patients with multivessel coronary artery disease (MVD) who underwent primary percutaneous coronary intervention (PCI) with culprit-only or multivessel PCI. We investigated 1-year clinical outcomes between biodegradable-polymer (BP)-coated biolimus-eluting stent (BES) and durable-polymer (DP)-coated DES in STEMI patients with MVD who underwent two different reperfusion strategies. Methods A total of 4255 patients were enrolled and divided into two groups, a culprit-only (n = 2571, BP- [n = 264] or DP-DES [n = 2307]) or a multivessel PCI group (n = 1684, BP- [n = 145] or DP-DES [n = 1539]). The primary endpoint was major adverse cardiac events (MACE) defined as all-cause death, recurrent myocardial infarction (re-MI), and total repeat revascularization. The secondary endpoint was the incidence of definite or probable stent thrombosis (ST). Results BP-BES and DP-DES showed a similar 1-year adjusted hazard ratio (HR) for MACE (culprit-only, adjusted hazard ratio [HR], 1.114; p = 0.740; multivessel, HR, 0.564; p = 0.167) and ST (culprit-only, HR, 1.110, p = 0.891; multivessel, HR, 0.375; p = 0.402). The adjusted HR for all-cause death, re-MI, and repeat revascularization were similar between the two groups. In the total population, the culprit-only PCI group showed a higher incidence of total repeat revascularization than the multivessel PCI group. Conclusions BP-BES and DP-DES showed comparable safety and efficacy in STEMI patients with MVD who underwent primary PCI with two different reperfusion strategies during a 1-year follow-up period.

Data concerning the clinical impact of combination therapy with β-blockers (BBs) + angiotensin-converting enzyme inhibitors (ACEIs) compared with BBs + angiotensin-receptor blockers (ARBs) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) are limited. We compared the clinical outcomes at 2 years between these two combination therapies. We enrolled 23,978 patients with AMI who underwent successful PCI with DES between January 2005 and June 2015 from the Korea AMI Registry (KAMIR) and divided them into the two groups: BB + ACEI (n = 17,310) and BB + ARB (n = 6668). The primary endpoint was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR. The secondary endpoints were the cumulative incidences of individual components of MACE and target vessel failure (TVF), a composite of death related to the target vessel, re-MI, or clinically driven TVR. The relative risk of MACE was higher in the BB + ARB group than in the BB + ACEI group after propensity score-matched (PSM) analysis (hazard ratio [HR] 1.204; 95% confidence interval [CI] 1.057–1.370; p = 0.005). The relative risks of all-cause death (HR 1.435 [95% CI 1.117–1.845]; p = 0.005), cardiac death (HR 1.733 [95% CI 1.253–2.396]; p = 0.001), TVR (HR 1.437 [95% CI 1.157–1.784]; p = 0.001), and TVF (HR 1.231 [95% CI 1.065–1.424]; p = 0.005) were also higher in the BB + ARB group after PSM. The BB + ACEI group demonstrated reduced cumulative incidences of MACE, all-cause death, cardiac death, TVR, and TVF compared with the BB + ARB group in patients with AMI who underwent successful PCI with DES during a 2-year follow-up period.

We compared the clinical impact of renin-angiotensin system inhibitors (RASI) on long-term clinical outcomes between ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) after successful percutaneous coronary intervention (PCI) with drug eluting stents (DES) because of the paucity of published data.A total of 24,960 acute myocardial infarction (AMI) patients who underwent PCI with DES and were prescribed the RASI were enrolled and divided into two groups, the STEMI group (n = 14,061) and the NSTEMI group (n = 10,899). The clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, cardiac death (CD), recurrent myocardial infarction (re-MI), total coronary revascularization (target lesion revascularization [TLR], target vessel revascularization [TVR], non-TVR) during 2 years.After propensity score-matched (PSM) analysis, two PSM groups (6762 pairs, n = 13,524, C-statistic = 0.682) were generated. All-cause death (hazard ratio [HR], 1.386; 95% confidence interval [CI], 1.114-1.725; p = 0.003) and CD (HR, 1.358; 95% CI, 1.041-1.770; p = 0.024) rates were significantly higher in NSTEMI patients. However, the incidence of MACE, re-MI, total revascularization, TLR, TVR, non-TVR was not significantly different between the two groups. In addition, old age (≥65years), decreased left ventricular ejection fraction (50%), hypertension, creatine kinase isoenzyme level, cardiogenic shock, cardiopulmonary resuscitation on admission, and PCI within 24 h were common significant independent risk factors of all-cause death and CD.The mortality reduction capability of RASI was more prominent in the STEMI patients compared with the NSTEMI patients.

Background The comparative clinical outcomes between prediabetes and type 2 diabetes mellitus (T2DM) in older adults with AMI in the era of newer-generation drug-eluting stents (DES) are limited. We investigated the 2-year clinical outcomes of these patients. Methods A total of 5492 AMI patients aged ≥65 years were classified into three groups according to their glycemic status: normoglycemia (group A: 1193), prediabetes (group B: 1696), and T2DM (group C: 2603). The primary outcome was the occurrence of major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization. The secondary outcome was stent thrombosis (ST). Results The primary and secondary outcomes cumulative incidences were similar between the prediabetes and T2DM groups. In both the prediabetes and T2DM groups, the cumulative incidences of MACE (adjusted hazard ratio [aHR]: 1.373; p = 0.020 and aHR: 1.479; p = 0.002, respectively) and all-cause death or MI (aHR: 1.436; p = 0.022 and aHR: 1.647; p = 0.001, respectively) were significantly higher than those in the normoglycemia group. Additionally, the cumulative incidence of all-cause death in the T2DM group was significantly higher than that in the normoglycemia group (aHR, 1.666; p = 0.003). Conclusions In this retrospective study, despite the 2-year clinical outcomes of the patients with prediabetes and T2DM in the older adults were worse than those in the normoglycemia group; they were similar between the prediabetes and T2DM groups. Hence, comparable treatment strategies should be strengthened between prediabetes and T2DM in older adults with AMI. Trial registration Retrospectively registered.

Background: We compared the 2-year clinical outcomes between prediabetes and type 2 diabetes mellitus (T2DM) according to the pre-percutaneous coronary intervention (PCI) thrombolysis in myocardial infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction. Methods: Overall, 6448 STEMI patients were divided into two groups: pre-PCI TIMI 0/1 group ( n = 4854) and pre-PCI TIMI 2/3 group ( n = 1594). They were further divided into patients with normoglycemia, prediabetes, and T2DM. The major endpoint was major adverse cardiac events (MACEs), defined as all-cause death, recurrent myocardial infarction, or any repeat revascularization. Results: In the pre-PCI TIMI 0/1 group, all-cause death rate was higher in both prediabetes (adjusted hazard ratio [aHR]: 1.633, p = 0.045) and T2DM (aHR: 2.064, p = 0.002) groups than in the normoglycemia group. In the pre-PCI TIMI 2/3 group, any repeat revascularization rate was also higher in both prediabetes (aHR: 2.511, p = 0.039) and T2DM (aHR: 3.156, p = 0.009) than normoglycemia. In each group (pre-PCI TIMI 0/1 or 2/3), the MACEs and all other clinical outcomes rates were similar between the prediabetes and T2DM groups. Conclusions: Prediabetes showed comparable worse clinical outcomes to those of T2DM regardless of the pre-PCI TIMI flow grade.

Objectives Although drug-coated balloons (DCBs) are established for de-novo lesions in small coronary arteries, the impact of DCB treatment according to the reference vessel diameter (RVD) remains poorly defined. This study aimed to evaluate the angiographic and long-term clinical outcomes of DCB treatment for de-novo coronary lesions according to RVD. Methods and results A total of 227 patients were retrospectively enrolled and stratified according to an RVD >2.5 mm [nonsmall vessel disease (NSVD) group, n = 100] and ≤2.5 mm [small vessel disease (SVD) group, n = 127]. The primary endpoint was late lumen loss (LLL) at a 6-month follow-up, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization and target vessel thrombosis). The LLL among the 206 patients (90.8%) returning for scheduled angiography at 6 month was similar (NSVD, 0.03 ± 0.22 mm vs. SVD, 0.06 ± 0.25 mm; P = 0.384). TVF was also comparable in both groups at a median follow-up of 3.4 years (NSVD, 7.0 vs. SVD, 7.9 %; P = 0.596). At baseline, there were numerically more dissections in the SVD group compared to the NSVD group (47.2 vs. 35.0 %; P = 0.064); however, most of these had disappeared in both groups at a 6-month follow-up. In a multivariable analysis, the presence of dissection was not associated with LLL or TVF in either group. Conclusions The safety and efficacy of DCB treatment for de-novo coronary lesions, in terms of LLL and TVF, was unrelated to RVD.

Because of a paucity of published data, we compared the 2-year major clinical outcomes between pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade 0/1 (pre-TIMI flow grade [pre-TIMI] 0/1) group and pre-PCI TIMI flow grade 2/3 (pre-TIMI 2/3) group in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent successful implantation of newer-generation drug-eluting stent. A total of 7506 NSTEMI patients were divided into 2 groups: pre-TIMI 0/1 group (n = 3157) and pre-TIMI 2/3 group (n = 4349). The primary outcome was major adverse cardiac events defined as all-cause death, recurrent myocardial infarction, or any repeat revascularization. The secondary outcome was stent thrombosis (ST). After propensity score-matched (PSM) analysis, 2 PSM groups (2473 pairs, n = 4946, C-statistic = 0.684) were generated. Major adverse cardiac events (hazard ration [HR], 1.294; 95% confidence interval [CI]: 1.065–1.572; P = .009), all-cause death (HR, 1.559, P = .003), cardiac death (HR: 1.641, P = .005), and all-cause death or MI (HR: 1.531, P = .001) rates were significantly higher in the pre-TIMI 0/1 group than in the pre-TIMI 2/3 group. Moreover, these differences were more prominent during the first 1 month after the index PCI. However, the cumulative incidences of recurrent myocardial infarction, any revascularization, and ST were similar between the 2 groups. Among a contemporary cohort of NSTEMI, these data suggest that the presence of a pre-PCI patency of the infarct-related artery showed better mortality reduction capacity than those with a lack of patency.

Introduction. Biolimus-eluting stents (BES) are known to be superior to bare-metal stents. This study aims to evaluate the safety and efficacy of BES compared to other drug-eluting stents (DES) based on big data from the Korea Acute Myocardial Infarction Registry (KAMIR). Methods. The study analyzed a total of 9,759 acute myocardial infarction (AMI) patients who underwent percutaneous coronary intervention (PCI) with DES. Total death, cardiac death, recurrent MI, revascularization, stent thrombosis, target lesion failure (TLF, composite of cardiac death, recurrent myocardial infarction (MI), and target lesion revascularization), and major adverse cardiac events (MACE, composite of total death, recurrent MI, and revascularization) were analyzed in patients with AMI up to three years. Study populations were divided into BES (n = 2,020), everolimus-eluting stents (EES, n = 5,293), and zotarolimus-eluting stents (ZES, n = 2,446) groups. Results. To adjust baseline potential confounders, an inverse probability weighting (IPTW) analysis was performed. After IPTW, at three years, total death (7.2%, 8.6%, and 9.5%, P < 0.001 ), cardiac death (4.1%, 5.3%, and 6.6%, P < 0.001 ), recurrent MI (1.6%, 2.6%, and 3.2%, P < 0.001 ), TLF (6.5%, 8.1%, and 9.1%, P < 0.001 ), and MACE (15.8%, 17.5%, and 18.2%, P < 0.001 ) were lowest in the BES group compared with the other DES groups in AMI patients. During the 3-year clinical follow-up, the BES group showed better outcomes of MACE (hazard ratio (HR), 0.773; 95% confidence interval (CI), 0.676–0.884; P < 0.001 ), TLF (HR, 0.659; 95% CI, 0.538–0.808; P < 0.001 ), total death (HR, 0.687; 95% CI, 0.566–0.835; P < 0.001 ), and cardiac death (HR,0.593; 95% CI, 0.462–0.541; P < 0.001 ) than the EES groups. Conclusions. In this study, BES was superior to EES or ZES in reducing total death, cardiac death, TLF, and MACE in AMI patients.

Long-term clinical outcomes in patients with acute myocardial infarction (AMI) and prediabetes or diabetes who received &szlig, blockers (BB) and renin&ndash, angiotensin system inhibitor (RASI) therapy after successful newer-generation drug-eluting stent (DES) implantation are limited. We compared the two-year clinical outcomes in such patients. A total of 9466 patients with AMI in the Korea AMI Registry were classified into six groups according to their glycemic status and presence or absence of BB + RASI therapy: normoglycemia and BB + RASI users (n = 2217) or nonusers (n = 243), prediabetes and BB + RASI users (n = 2601) or nonusers (n = 306), and diabetes and BB + RASI users (n = 3682) or nonusers (n = 417). The primary endpoint was major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat revascularization, and the secondary endpoint was the cumulative incidence of hospitalization for heart failure (HHF). In patients with BB + RASI, despite similar primary and secondary clinical points between the prediabetes and diabetes groups, the cumulative incidence of Re-MI (adjusted hazard ratio: 1.660, 95% confidence interval: 1.000&ndash, 2.755, p = 0.020) was higher in the diabetes group than in the prediabetes group. In all three different glycemic groups, BB + RASI users showed reduced MACEs, cardiac death, and HHF compared to those of BB + RASI nonusers. In this retrospective observational registry study, BB + RASI therapy showed comparable clinical outcomes except for Re-MI between prediabetes and diabetes in patients with AMI during a two-year follow-up period.

Elderly patients treated with percutaneous coronary intervention (PCI) have a higher risk of both ischemic and bleeding complications than younger patients. However, few studies have reported how genetic information of elderly patients treated with PCI affects clinical outcomes. We investigated the impact of genetic variants on clinical outcomes in elderly patients. Correlations between single-nucleotide polymorphisms (CYP2C19 and P2Y12 receptor gene G52T polymorphism) and clinical outcomes were analyzed in 811 elderly patients (≥75 years of age) from a prospective multicenter registry. The primary endpoint was a composite of myocardial infarction and death. Secondary endpoints were an individual event of death, cardiac death, myocardial infarction, stent thrombosis, target lesion revascularization, stroke, and major bleeding (Bleeding Academic Research Consortium ≥3). Regarding CYP2C19, patients with poor metabolizers had a significantly higher risk for the primary endpoint (hazard ratio [HR] 2.43; 95% confidence interval [95% CI] 1.12-5.24; p=0.024) and secondary endpoints (death and cardiac death). Regarding P2Y12 G52T, the TT group had a significantly higher occurrence of major bleeding than the other groups (HR 3.87; 95% CI 1.41-10.68; p=0.009). In conclusion, poor metabolizers of CYP2C19 and TT groups of P2Y12 G52T may be significant predictors of poor clinical outcomes in elderly patients.

Background: T2 gallbladder cancer (GBC) is subdivided into T2a and T2b by the American Joint Committee on Cancer (AJCC) 8th edition. However, there is a lack of evidence for the prognostic significance of tumor location and validation with large-scale studies is needed. The aims of this study were to investigate the clinical features and clinical outcomes of T2 GBC according to tumor location and determine the prognostic significance of tumor location and an appropriate surgical strategy. Methods: Between 2000 and 2014 the Korea Tumor Registry System Biliary Pancreas (KOTUS-BP) database was used to identify and enroll a total 707 patients with pathologically diagnosed T2 GBC who underwent curative resection. Clinicopathological findings and long-term follow-up results were analyzed. Results: The incidence of lymph node metastasis in T2b was significantly higher than that of T2a tumors (37.9% vs. 29.5%, p = 0.032). The 5-year disease-specific survival of T2a was better than that of T2b tumors (74.8% vs. 65.4%, p = 0.019). There was no significant survival difference in T2a between extended cholecystectomy and simple cholecystectomy with lymph node dissection (81.8% vs. 73.7%, p = 0.361). However, there was a better survival trend for T2b tumor after extended cholecystectomy (71.7% vs. 59.3%, p = 0.057). Adjuvant chemotherapy was associated with improved survival for patients with lymph node metastasis in T2a (72.1% vs. 56.9, p = 0.022) and in T2b (68.2 vs. 48.5, p &lt, 0.001). Multivariate analysis revealed that lymph node metastasis was the only significant poor prognostic factor (Hazard ratio 3.222, 95% confidential interval 1.960&ndash, 4.489, 0.001). Conclusions: For T2 GBC, tumor location was not an independent prognostic factor. Lymph node metastasis was a significant poor prognostic factor and adjuvant chemotherapy should be considered for the patients with lymph node metastasis.

Studies comparing long-term clinical outcomes of statin treatment between acute myocardial infarction (AMI) patients with prediabetes and those with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) with the newer-generation drug-eluting stents (DESs) are limited. We compared 2-year clinical outcomes between these patients.A total of 11,962 AMI patients were classified as statin users (n = 10,243) and statin nonusers (n = 1719). Thereafter, statin users and nonusers were further divided into the normoglycemia, prediabetes, and T2DM groups. The major outcome was the occurrence of major adverse cardiac event (MACE) defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat coronary revascularization.After statin treatment, the cumulative incidences of MACE (P = .314), all-cause death, cardiac death (CD), Re-MI, and any repeat revascularization were similar between the prediabetes and T2DM groups. However, the cumulative incidences of MACE (P = .025) and all-cause death (P = .038) in the prediabetes group and those of MACE (P = .001), all-cause death (P = .009), and CD (P = .048) in the T2DM group were significantly higher than those in the normoglycemia group. Moreover, in all the 3 glycemic groups, the cumulative incidences of MACE, all-cause death, and CD were significantly higher among statin nonusers than among statin users.This study revealed that AMI patients with prediabetes had worse clinical outcomes than those with normoglycemia and comparable to those with T2DM after 2-year statin treatment. However, further studies are warranted to confirm the current findings.

To evaluate clinical implication of prediabetes, we compared a 2-year major clinical outcome including patient-oriented composite outcomes (POCOs), stent thrombosis (ST), and stroke between prediabetes and diabetes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). A total of 4097 patients with STEMI and MVD (normoglycemia [group A: 1001], prediabetes [group B: 1518], and diabetes [group C: 1578]) who received drug-eluting stents were evaluated. Patient-oriented composite outcomes were defined as all-cause death, recurrent myocardial infarction (MI), or any repeat revascularization. The cumulative incidences of POCOs, ST, and stroke were similar between groups B and C. The cumulative incidences of all-cause death (adjusted hazard ratio [aHR]: 1.483; 95% CI: 1.027-2.143; P = .036) and all-cause death or MI (aHR: 1.429, 95% CI: 1.034-1.974; P = .031) were higher in group B than in group A. The cumulative incidences of all-cause death (aHR: 1.563; 95% CI: 1.089-2.243; P = .015), cardiac death (aHR: 1.661; 95% CI: 1.123-2.457; P = .011), and all-cause death or MI were higher in group C than in group A. In conclusion, prediabetes could potentially have a similar impact as diabetes on major clinical outcomes in patients with STEMI and MVD.

We investigated the effects of stent generation on 2-year clinical outcomes between prediabetes and diabetes patients after acute myocardial infarction (AMI). A total of 13,895 AMI patients were classified into normoglycemia (group A: 3673), prediabetes (group B: 5205), and diabetes (group C: 5017). Thereafter, all three groups were further divided into first-generation (1G)-drug-eluting stent (DES) and second-generation (2G)-DES groups. Patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcome. Stent thrombosis (ST) was the secondary outcome. In both prediabetes and diabetes groups, the cumulative incidences of POCOs, any repeat revascularization, and ST were higher in the 1G-DES than that in the 2G-DES. In the diabetes group, all-cause death and cardiac death rates were higher in the 1G-DES than that in the 2G-DES. In both stent generations, the cumulative incidence of POCOs was similar between the prediabetes and diabetes groups. However, in the 2G-DES group, the cumulative incidences of Re-MI and all-cause death or MI were significantly higher in the diabetes group than that in the prediabetes group. To conclude, 2G-DES was more effective than 1G-DES in reducing the primary and secondary outcomes for both prediabetes and diabetes groups.

This study investigated the impacts of renin–angiotensin system inhibitors (RASIs) on 2-year clinical outcomes in diabetes and dyslipidemic acute myocardial infarction (AMI) patients after a successful percutaneous coronary intervention (PCI) using newer-generation drug-eluting stents (DESs). A total of 16,997 AMI patients were enrolled, and divided into four groups based on the presence or absence of diabetes and dyslipidemia as follows: diabetes –/dyslipidemia –(group A, 11,132 patients), diabetes +/dyslipidemia – (group B, 3,860 patients), diabetes –/dyslipidemia + (group C, 1,328 patients), and diabetes +/dyslipidemia + (group D, 677 patients). The clinical endpoint was the occurrence of major adverse cardiac events (MACEs), the composite of total death, recurrent myocardial infarction (re-MI), and any repeat revascularization, including target lesion revascularization (TLR), target vessel revascularization (TVR), and non-target vessel revascularization (non-TVR). After RASIs therapy, the cumulative incidences of MACEs (adjusted hazard ratio [aHR], 1.330; 95% confidence interval [CI], 1.022–1.732; P = .034), any repeat revascularization (aHR, 1.584; 95% CI, 1.092–2.298; P = .015), TLR, and TVR were significantly higher in group B than group C. However, the cumulative incidences of all-cause death, cardiac death, re-MI, and non-TVR were similar in groups B and C. In this study, under the newer-generation DESs era, repeat revascularization rate reduction benefit of RASIs therapy in diabetic AMI patients was lesser than that in dyslipidemic AMI patients. However, larger randomized controlled studies are needed to confirm these results in the future.

Background: Limited data are available comparing the combined effects of statins and renin–angiotensin system inhibitor (RASI) between patients with ST-segment elevation myocardial infarction (STEMI) and those with non-STEMI (NSTEMI). We compared the effects of statins combined with RASI in STEMI and NSTEMI patients after stent implantation during a long-term follow-up period. Methods: A total of 21,890 acute myocardial infarction (AMI) patients who underwent successful stent implantation and who received statins with RASI were enrolled. They were separated into the STEMI group (n = 12,490) and the NSTEMI group (n = 9400). The major clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization. Results: Two propensity score-matched (PSM) groups (5891 pairs, n = 11782, C-statistic = 0.821) were generated. Even though the cumulative incidences of MACE, re-MI, total repeat revascularization were similar between the two groups, the cumulative incidences of all-cause death (hazard ratio [HR] 1.407; 95% confidence interval [CI] 1.106–1.790; p = 0.005) and cardiac death (HR 1.311; 95% CI 1.983–1.749; p = 0.046) were significantly higher in the NSTEMI group. Conclusions: In this study, statin with RASI combination therapy was more beneficial to the STEMI patients than to the NSTEMI patients in reducing all-cause death and cardiac death.

Background: Previous work has highlighted the importance of the neutrophil-to-lymphocyte ratio (NLR) and the difference in the ward-to-catheterization laboratory systolic blood pressure (ΔSBP) in prognostic stratification after acute coronary syndrome. However, there is paucity of data regarding the added value of combining these two variables to predict 5-year major clinical outcomes after percutaneous coronary intervention. Methods: A total of 1188 patients were classified into four groups according to the NLR and ΔSBP (high vs. low) using cutoffs derived from an analysis of receiver operating characteristic curves. A NLR > 3.0 and a ΔSBP > 25 mmHg were considered high values. The primary endpoint was the composite of all-cause death, cardiac death, and non-fatal myocardial infarction. The secondary endpoint was the composite of target lesion revascularization, target vessel revascularization, and incidence of cerebrovascular accidents. Results: The incidence of the primary endpoint was significantly higher in the high NLR and ΔSBP group than in the other three groups (2.2% vs. 4.7% vs. 4.3% vs. 13.2%, p < 0.001). The incidence of the secondary endpoint was similar among the four groups. Incorporation of high NLR and high ΔSBP into a model with conventional and meaningful clinical and procedural risk factors increased the C-statistics in predicting the primary endpoint (0.575 to 0.635, p = 0.002). Conclusions: The power to predict the primary endpoint after drug-eluting stent implantation at the 5-year follow-up was improved by combining NLR and ΔSBP.

Clinical benefits of bioresorbable vascular scaffold (BVS) implantation for long coronary lesions were not sufficiently evaluated. The efficacy and safety of BVS and metallic everolimus-eluting stent (EES) were compared for the treatment of long coronary narrowings. A total of 341 patients with diffuse long lesions (requiring device length ≥28 mm) were randomized to receive either BVS (n = 171) or EES (n = 170) implantation. The primary endpoint was major adverse cardiovascular events which included death from cardiac cause, myocardial infarction, device thrombosis, or ischemia-driven target-lesion revascularization at 12 months. The trial was terminated early because the manufacturer stopped supplying BVS. The mean lesion length was 32.2 ± 13.1 mm in the BVS group and 35.3 ± 13.0 mm in the EES group. The 12-month follow-up was completed in 332 patients (97.4%). At 12 months, the primary endpoint events occurred in 2 patients (1.2%) in the BVS group and in 4 patients (2.4%) in the EES group (hazard ratio = 0.49, 95% confidence interval = 0.09 to 2.67, p = 0.398). Definite or probable device thrombosis occurred in 1 patient (0.6%) in the BVS group and 1 patient (0.6%) in the EES group (hazard ratio = 1.00, 95% confidence interval = 0.06 to 15.94, p = 0.998). In conclusion, in patients with long native coronary artery disease, significant differences between BVS and EES were not observed regarding the primary composite endpoint of death from cardiac cause, myocardial infarction, device thrombosis, or target-lesion revascularization at 12 months. However, due to the early termination of this trial and a low number of events, the results cannot be considered clinically relevant (clinicalTrials.gov Identifier: NCT02796157 ).

Objective. To compare major clinical outcomes after successful percutaneous coronary intervention (PCI) with first-generation (1G) drug-eluting stents (DES) and second-generation (2G) DES in patients with acute myocardial infarction (AMI) and prediabetes. Background. Patients with prediabetes are associated with an increased incidence of coronary artery disease. The relative superiority of 1G- and 2G-DES in these patients is not well established. Methods. A total of 4997 patients with AMI and prediabetes were divided into two groups: the 1D-DES group (n = 726) and the 2G-DES group (n = 4271). The primary outcomes were the patient-oriented composite outcomes (POCOs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any disease revascularization at 2-year follow-up. The secondary outcome was probable or definite stent thrombosis (ST). Results. After propensity score-matching (PSM) analysis, two PSM groups (698 pairs, n = 1396, C-statistics = 0.725) were generated. The cumulative incidence rates of POCOs (hazard ratio (HR): 1.467; 95% confidence interval (CI): 1.068–2.015; p=0.018), any disease revascularization (HR: 2.259; 95% CI: 1.397–3.654; p=0.001), and ST (HR: 4.361; 95% CI: 1.243–15.30; p=0.021) in the 1G-DES group were significantly higher than those in the 2G-DES group. However, the cumulative incidence rates of all-cause death, cardiac death, and Re-MI were similar between the two groups. Conclusions. In patients with AMI and prediabetes, 2G-DES implantation was more efficacious than 1G-DES implantation over a 2-year follow-up period. However, further studies are needed to confirm these results.

Objective There is a scarcity of comparative studies between Endeavor Resolute®-zotarolimus-eluting stent (R-ZES) and Resolute Integrity®-ZES (I-ZES) during long-term follow-up periods. Although the stent alloy and the polymer of these two ZESs are similar, the platform and the design of these two stents are different. This study was conducted to compare the efficacy and safety of these two different ZESs in the all-comer Korean patients who underwent percutaneous coronary intervention (PCI) during a 3-year follow-up period. Methods This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. In this single-center, retrospective, and all-comer patients' cohort study, a total of 889 patients who underwent PCI with R-ZES (n=394) or I-ZES (n=495) were enrolled. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, nonfatal myocardial infarction (MI), any repeat revascularization including target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR, and the secondary endpoint was stent thrombosis (ST) at 3 years. Results To adjust for any potential confounders, the propensity score-adjusted multivariable analysis was performed using the logistic regression model (C-statistics=0.689). The cumulative incidence rates of MACEs [adjusted hazard ratio (aHR), 1.341; 95% confidence interval (CI), 0.615-2.922; p=0.461], all-cause death, nonfatal MI, any repeat revascularization, and ST (aHR, 2.090; 95% CI, 0.163-26.77; p=0.571) were similar between the two groups during the 3-year follow-up period. Conclusion R-ZES and I-ZES demonstrated comparable efficacy and safety after PCI during a 3-year follow-up period. However, these results can perhaps be more precisely defined by other large and long-term follow-up studies in the future. (Anatol J Cardiol 2020; 23: 268-76).

Background Limited studies focused on long-term outcomes of statin therapy in patients with acute myocardial infarction (AMI) with or without dyslipidemia after percutaneous coronary intervention (PCI) in the era of new-generation drug-eluting stents (DES). We thought to investigate 2-year clinical outcomes of statin therapy in these patients. Methods A total of 18,137 eligible AMI patients (from the Korea AMI Registry [KAMIR]) were finally enrolled and divided into four groups according to the presence or absence of dyslipidemia and statin therapy (dyslipidemia+/statin- [group A, 309 patients], dyslipidemia+/statin+ [group B, 2094 patients], dyslipidemia-/statin- [group C, 672 patients], dyslipidemia-/statin+ [group D, 15062 patients]). The primary outcome was major adverse cardiac event (MACE) defined as all-cause death, myocardial infarction (MI) and revascularization. Results During the 2-year follow-up period, the cumulative incidence of MACE in the group A was higher than the group B (adjusted hazard ratio [HR], 2.207; 95% confidence interval (CI), 1.098-3.743; p = .024) and the group D (adjusted HR, 2.110; 95% CI, 1.240-3.593, p = .006). This significantly increased incidence of MACE caused by the higher cumulative incidences of all-cause death and cardiac death (CD) in the group A compared with groups B and D. However, the cumulative incidences of MI and revascularization were not significantly different among these four groups. Conclusion Statin therapy demonstrated significantly reduced incidences of MACE, all-cause death and CD compared with non-users after PCI in AMI patients with or without dyslipidemia during 2-year follow-up period in the era of new-generation DES.

Aim To investigate the comparative effectiveness of renin-angiotensin system inhibitor (RASI) therapy on major clinical outcomes in patients with acute myocardial infarction (AMI) and prediabetes or diabetes after successful percutaneous coronary intervention (PCI) with newer-generation drug-eluting stents (DESs). Methods A total of 11,962 patients with AMI were divided into six groups according to glycemic status and the presence or absence of RASI therapy: normoglycemia (n = 3,080; RASI+ [n = 2,496], RASI− [n = 584]), prediabetes (n = 3,709; RASI+ [n = 2,944], RASI− [n = 765]), and diabetes (n = 5,173; RASI+ [n = 4,133], RASI− [n = 1,040]). The major endpoint was major adverse cardiac events (MACEs), defined as all-cause death, recurrent myocardial infarction (re-MI), or any repeat revascularization. Results After adjustment, in RASI users, the cumulative incidence of re-MI of the diabetes group was significantly higher than that of the prediabetes group (aHR, 1.999; 95% CI, 1.153–3.467; p = 0.014). However, the cumulative incidences of MACEs, all-cause death, and any repeat revascularization were similar between the two groups during a 2-year follow-up period. Conclusions In the era of newer-generation DESs, RASI therapy did not reduce re-MI in patients with AMI and diabetes in this study.

There are limited data comparing the clinical outcomes among new-generation drug-eluting stents (DES) in acute myocardial infarction (AMI) patients with dyslipidemia after percutaneous coronary intervention (PCI). We thought to investigate 2-year clinical outcomes among durable-polymer (DP)-coated stents [zotarolimus eluting (ZES) and everolimus eluting (EES)] and biodegradable-polymer (BP)-coated biolimus-eluting stent (BES) in dyslipidemic AMI patients after PCI. Finally, a total 2403 enrolled patients were divided into ZES (n = 953), EES (n = 1145) or BES (n = 305) group. The primary endpoint was major adverse cardiac events (MACE) defined as total death (TD), cardiac death (CD), myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and non-TVR. The secondary endpoint was the incidence of definite or probable stent thrombosis (ST). The 2-year adjusted hazard ratio (HR) of MACE for ZES vs. EES [HR, 1.066; 95% confidence interval (CI) 0.752-1.511; p = 0.720], ZES vs. BES (HR 0.933; 95% CI 0.565-1.541; p = 0.786), EES vs. BES (HR 1.876; 95% CI 0.535-1.436; p = 0.600) and ZES/EES vs. BES (HR 0.929; 95% CI 0.591-1.462; p = 0.751) was similar. The cumulative incidences of ST were comparable (ZES vs. EES vs. BES = 1.1% vs. 0.9% vs. 1.1%, p = 0.675) and adjusted HR was not different. In addition, the 2-year adjusted HR of TD, CD, MI, TLR, TVR, and non-TVR was similar. The AMI patients with dyslipidemia receiving ZES, EES, or BES after PCI showed comparable safety and efficacy during 2-year follow-up periods. Therefore, DP-DES or BP-DES is equally acceptable in dyslipidemic AMI patients during PCI.

Upon liver intoxication with malnutrition or high-fat diet feeding, fibrinogen is synthesized by hepatocytes and secreted into the blood in human and mouse. Its primary function is to occlude blood vessels upon damage and thereby stop excessive bleeding. High fibrinogen levels may contribute to the development of pathological thrombosis, which is one mechanism linking fatty liver disease with cardiovascular disease. Our previous results present ERRγ as key regulator of hepatocytic fibrinogen gene expression in human. In a therapeutic approach, we now tested ERRγ inverse agonist GSK5182 as regulator of fibrinogen levels in mouse hyperfibrinogenemia caused by diet-induced obesity and in mouse hepatocytes. ACEA, a CB1R agonist, up-regulated transcription of mouse fibrinogen via induction of ERRγ, whereas knockdown of ERRγ attenuated the effect of ACEA (10 µM) on fibrinogen expression in AML12 mouse hepatocytes. Deletion analyses of the mouse fibrinogen γ (FGG) gene promoter and ChIP assays revealed binding sites for ERRγ on the mouse FGG promoter. ACEA or adenovirus ERRγ injection induced FGA, FGB and FGG mRNA and protein expression in mouse liver, while ERRγ knockdown with Ad-shERRγ attenuated ACEA-mediated induction of fibrinogen gene expression. Moreover, mice maintained on a high-fat diet (HFD) expressed higher levels of fibrinogen, whereas cannabinoid receptor type 1 (CB1R)-KO mice fed an HFD had nearly normal fibrinogen levels. Finally, GSK5182 (40 mg/kg) strongly inhibits the ACEA (10 mg/kg) or HFD-mediated induction of fibrinogen level in mice. Taken together, targeting ERRγ with its inverse agonist GSK5182 represents a promising therapeutic strategy for ameliorating hyperfibrinogenemia.