Clinical safety and effectiveness of the Genoss drug-eluting stent in real-world clinical practice.

BACKGROUND/AIMS: The Genoss DES™ is a novel, biodegradable, polymer-coated, sirolimus-eluting stent with a cobalt- chromium stent platform and thin strut. Although the safety and effectiveness of this stent have been previously investigated, real-world clinical outcomes data are lacking. Therefore, the aim of this prospective, multicenter trial was to evaluate the clinical safety and effectiveness of the Genoss DES™ in all-comer patients undergoing percutaneous coronary intervention. METHODS: The Genoss DES registry is a prospective, single-arm, observational trial for evaluation of clinical outcomes after Genoss DES™ implantation in all-comer patients undergoing percutaneous coronary intervention from 17 sites in South Korea. The primary endpoint was a device-oriented composite outcome of cardiac death, target vessel-related myocardial infarction (MI), and clinically driven target lesion revascularization (TLR) at 12 months. RESULTS: A total of 1,999 patients (66.4 ± 11.1 years of age; 72.8% male) were analyzed. At baseline, 62.8% and 36.7% of patients had hypertension and diabetes, respectively. The implanted stent number, diameter, and length per patient were 1.5 ± 0.8, 3.1 ± 0.5 mm, and 37.0 ± 25.0 mm, respectively. The primary endpoint occurred in 1.8% patients, with a cardiac death rate of 1.1%, target vessel-related MI rate of 0.2%, and clinically driven TLR rate of 0.8%. CONCLUSION: In this real-world registry, the Genoss DES™ demonstrated excellent safety and effectiveness at 12 months among all-comer patients undergoing percutaneous coronary intervention. These findings suggest that the Genoss DES™ may be a viable treatment option for patients with coronary artery disease.

Perioperative Antiplatelet Strategy in Patients Undergoing Noncardiac Surgery Within One Year After Percutaneous Coronary Intervention.

BACKGROUND: The optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. METHODS: Patients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. RESULTS: Among 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). CONCLUSIONS: The APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.

Tratamiento antiagregante plaquetario doble tras la intervención coronaria percutánea del tronco coronario izquierdo / Dual antiplatelet therapy after percutaneous coronary intervention for left main coronary artery disease

Introducción y objetivos Son escasos los datos sobre la duración y el impacto pronóstico del tratamiento antiagregante plaquetario doble (TAPD) tras una intervención coronaria percutánea (ICP) del tronco coronario izquierdo (TCI) con stents farmacoactivos de segunda generación. El objetivo de este estudio es investigar los patrones de prescripción y el efecto pronóstico a largo plazo de la duración del TAPD en pacientes sometidos a ICP del TCI con stents farmacoactivos segunda generación. Métodos A partir de los datos individuales de los registros IRIS-MAIN y KOMATE, se incluyó a 1.827 pacientes sometidos a ICP del TCI con stents farmacoactivos de segunda generación de los que hubiese información válida sobre la duración del TAPD. El objetivo de eficacia fue la aparición de eventos cardiovasculares adversos mayores (MACE) (un combinado de muerte cardiaca, infarto de miocardio y trombosis del stent) y el de seguridad fue la presencia de hemorragia mayor según TIMI. Resultados Las duraciones del TAPD fueron <6 meses (n=273), de 6-12 meses (n=477), de 12-24 meses (n=637) y ≥ 24 meses (n=440). La mediana de la duración del seguimiento fue de 3,9 [intervalo intercuartílico, 3,01-5,00] años. El TAPD prolongado se asoció con menor incidencia de MACE. En el análisis de puntuación de propensión multigrupo, las HR ajustadas de los MACE fueron significativamente mayores con los TAPD de menos de 6 meses y de 6-12 meses (HR=4,51; IC95%, 2,96-6,88) frente al TAPD de 12-24 meses (HR=1,92; IC95%, 1,23-3,00). No hubo diferencias en la HR de hemorragia mayor entre los grupos evaluados. Conclusiones La duración del TAPD tras la ICP para la enfermedad del TCI es muy variable. Aunque debe considerarse en función de la situación clínica de cada paciente, un TAPD de menos de 12 meses se asoció con mayor incidencia de MACE (AU)

Introduction and objectives There are scarce data on the optimal duration and prognostic impact of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with second-generation drug-eluting stents for left main coronary artery (LMCA) disease. The aim of this study was to investigate the practice pattern and long-term prognostic effect of DAPT duration in patients undergoing PCI with second-generation drug-eluting stents for LMCA disease. Methods Using individual patient-level data from the IRIS-MAIN and KOMATE registries, 1827 patients undergoing PCI with second-generation drug-eluting stents for LMCA disease with valid information on DAPT duration were included. The efficacy outcome was major adverse cardiovascular events (MACE, a composite of cardiac death, myocardial infarction, and stent thrombosis) and the safety outcome was TIMI major bleeding. Results DAPT duration was <6 months (n=273), 6 to 12 months (n=477), 12 to 24 months (n=637), and ≥ 24 months (n=440). The median follow-up duration was 3.9 [interquartile range, 3.01-5.00] years. Prolonged DAPT duration was associated with lower incidences of MACE. In multigroup propensity score analysis, adjusted HR for MACE were significantly higher for DAPT <6 months and DAPT 6 to 12 months than for DAPT 12 to 24 months (HR, 4.51; 95%CI, 2.96-6.88 and HR 1.92; 95%CI, 1.23-3.00). There was no difference in HR for major bleeding among the assessed groups. Conclusions DAPT duration following PCI for LMCA disease is highly variable. Although the duration of DAPT should be considered in the context of the clinical situation of each patient, <12 months of DAPT was associated with higher incidence of MACE. Registration identifiers: NCT01341327; NCT03908463 (AU)

Dual antiplatelet therapy after percutaneous coronary intervention for left main coronary artery disease.

INTRODUCTION AND OBJECTIVES: There are scarce data on the optimal duration and prognostic impact of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with second-generation drug-eluting stents for left main coronary artery (LMCA) disease. The aim of this study was to investigate the practice pattern and long-term prognostic effect of DAPT duration in patients undergoing PCI with second-generation drug-eluting stents for LMCA disease. METHODS: Using individual patient-level data from the IRIS-MAIN and KOMATE registries, 1827 patients undergoing PCI with second-generation drug-eluting stents for LMCA disease with valid information on DAPT duration were included. The efficacy outcome was major adverse cardiovascular events (MACE, a composite of cardiac death, myocardial infarction, and stent thrombosis) and the safety outcome was TIMI major bleeding. RESULTS: DAPT duration was <6 months (n=273), 6 to 12 months (n=477), 12 to 24 months (n=637), and ≥ 24 months (n=440). The median follow-up duration was 3.9 [interquartile range, 3.01-5.00] years. Prolonged DAPT duration was associated with lower incidences of MACE. In multigroup propensity score analysis, adjusted HR for MACE were significantly higher for DAPT <6 months and DAPT 6 to 12 months than for DAPT 12 to 24 months (HR, 4.51; 95%CI, 2.96-6.88 and HR 1.92; 95%CI, 1.23-3.00). There was no difference in HR for major bleeding among the assessed groups. CONCLUSIONS: DAPT duration following PCI for LMCA disease is highly variable. Although the duration of DAPT should be considered in the context of the clinical situation of each patient, <12 months of DAPT was associated with higher incidence of MACE. Registration identifiers: NCT01341327; NCT03908463.

Machine learning models of clinically relevant biomarkers for the prediction of stable obstructive coronary artery disease.

Background: In patients with suspected obstructive coronary artery disease (CAD), evaluation using a pre-test probability model is the key element for diagnosis; however, its accuracy is controversial. This study aimed to develop machine learning (ML) models using clinically relevant biomarkers to predict the presence of stable obstructive CAD and to compare ML models with an established pre-test probability of CAD models. Methods: Eight machine learning models for prediction of obstructive CAD were trained on a cohort of 1,312 patients [randomly split into the training (80%) and internal validation sets (20%)]. Twelve clinical and blood biomarker features assessed on admission were used to inform the models. We compared the best-performing ML model and established the pre-test probability of CAD (updated Diamond-Forrester and CAD consortium) models. Results: The CatBoost algorithm model showed the best performance (area under the receiver operating characteristics, AUROC, 0.796, and 95% confidence interval, CI, 0.740-0.853; Matthews correlation coefficient, MCC, 0.448) compared to the seven other algorithms. The CatBoost algorithm model improved risk prediction compared with the CAD consortium clinical model (AUROC 0.727; 95% CI 0.664-0.789; MCC 0.313). The accuracy of the ML model was 74.6%. Age, sex, hypertension, high-sensitivity cardiac troponin T, hemoglobin A1c, triglyceride, and high-density lipoprotein cholesterol levels contributed most to obstructive CAD prediction. Conclusion: The ML models using clinically relevant biomarkers provided high accuracy for stable obstructive CAD prediction. In real-world practice, employing such an approach could improve discrimination of patients with suspected obstructive CAD and help select appropriate non-invasive testing for ischemia.

Impact of the Obesity Paradox Between Sexes on In-Hospital Mortality in Cardiogenic Shock: A Retrospective Cohort Study.

Background Several studies have shown that obesity is associated with better outcomes in patients with cardiogenic shock (CS). Although this phenomenon, the "obesity paradox," reportedly manifests differently based on sex in other disease entities, it has not yet been investigated in patients with CS. Methods and Results A total of 1227 patients with CS from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) registry in Korea were analyzed. The study population was classified into obese and nonobese groups according to Asian Pacific criteria (BMI ≥25.0 kg/m2 for obese). The clinical impact of obesity on in-hospital mortality according to sex was analyzed using logistic regression analysis and restricted cubic spline curves. The in-hospital mortality rate was significantly lower in obese men than nonobese men (34.2% versus 24.1%, respectively; P=0.004), while the difference was not significant in women (37.3% versus 35.8%, respectively; P=0.884). As a continuous variable, higher BMI showed a protective effect in men; conversely, BMI was not associated with clinical outcomes in women. Compared with patients with normal weight, obesity was associated with a decreased risk of in-hospital death in men (multivariable-adjusted odds ratio [OR], 0.63; CI, 0.43-0.92 [P=0.016]), but not in women (multivariable-adjusted OR, 0.94; 95% CI, 0.55-1.61 [P=0.828]). The interaction P value for the association between BMI and sex was 0.023. Conclusions The obesity paradox exists and apparently occurs in men among patients with CS. The differential effect of BMI on in-hospital mortality was observed according to sex. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Association of Light-Intensity Physical Activity With Mortality in the Older Population: A Nationwide Cohort Study.

Background: There is a paucity of information about mortality related to light-intensity physical activity (LPA) in the older population. We examine the associations between physical activity and mortality, focusing on the effect of light-intensity physical activity and the dose-response relationship between physical activity and mortality. Methods: We analyzed a total of 58,537 participants aged ≥ 65 years (mean age, 73.9 ± 5.8 years; male, 36.0%) in the Korean National Health Insurance Service database between 2009 and 2012. The Date of the end of follow-up was December 31, 2013. Individuals were divided into four categories according to physical activity intensity: totally sedentary (43.3%), LPA only (35.8%), LPA and moderate- to vigorous-intensity physical activity (MVPA) (16.3%), MVPA only (4.5%). Physical activity was quantified using standardized self-reported questionnaires which composed of the duration and frequency of physical activity. Results: During a mean follow-up of 39.6 ± 14.0 months, 5,651 (9.7%) deaths occurred. Compared with totally sedentary individuals, those in the LPA only, LPA and MVPA, and MVPA only groups showed 26% [hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.68-0.82], 27% (HR 0.73, 95% CI 0.63-0.84), and 34% (HR 0.66, 95% CI 0.54-0.79) lower all-cause mortality risk, showing an inverse relationship between physical activity intensity and mortality risk. In contrast, the LPA only, LPA and MVPA, and MVPA only groups represented a stronger inverse association with CV mortality (LPA: HR 0.76, 95% CI 0.62-0.92; LPA with MVPA: HR 0.74, 95% CI 0.55-0.999; MVPA, HR 0.57, 95% CI 0.37-0.87). Among participants performing LPA alone, participants performing less than the recommended dose of physical activity had lower all-cause mortality than those with sedentary activity (1-249 MET-min/week: HR 0.74, 95% CI 0.67-0.82, 250-499 MET-min/week: HR 0.65, 95% CI 0.59-0.72). Conclusion: Physical activity, even low doses of LPA, was associated with reduced mortality risk in the elderly population. This study may motivate sedentary individuals to engage in any physical activity for mortality benefits.

Prognostic Impact of Plasma Glucose on Patients With Cardiogenic Shock With or Without Diabetes Mellitus from the SMART RESCUE Trial.

Although the presence of hyperglycemia has been shown to affect the clinical outcome of patients with cardiogenic shock, the extent of hyperglycemia and its association with prognosis have not been fully addressed in a large population. A total of 1,177 consecutive patients with cardiogenic shock were enrolled from January 2014 to December 2018 at 12 hospitals in South Korea. The primary outcome was in-hospital mortality. Patients were divided into 4 groups according to their initial plasma glucose level in patients with diabetes mellitus (DM) (n = 752) and patients without DM (n=425); group 1 (≤8 mmol/L or 144 mg/100 ml), group 2 (8 to 12 mmol/L or 144 to 216 mg/100 ml), group 3 (12 to 16 mmol/L or 216 to 288 mg/100 ml), and group 4 (≥16 mmol/L or 288 mg/100 ml). The groups with higher admission plasma glucose were associated with lower systolic blood pressure and higher lactic acid levels in patients with and without DM. In-hospital mortality increased in groups with higher admission plasma glucose level in patients without DM (group 1:24.2%, group 2: 28.6%, group 3: 38.1%, group 4: 49.0%, p <0.01), whereas in patients with DM, mortality and admission plasma glucose level showed no significant association (group 1: 45%, group 2: 35.4%, group 3: 33.3%, group 4: 43.1%, p = 0.26). Even after multivariate analysis, high plasma glucose was an independent predictor of in-hospital mortality in patients without DM. In patients with cardiogenic shock, plasma glucose obtained at admission was associated with in-hospital mortality in patients without DM.

Ticagrelor Monotherapy After 3-Month Dual Antiplatelet Therapy in Acute Coronary Syndrome by High Bleeding Risk: The Subanalysis From the TICO Trial.

BACKGROUND AND OBJECTIVES: Identifying patients with high bleeding risk (HBR) is important when making decisions for antiplatelet therapy strategy. This study evaluated the impact of ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT) according to HBR in acute coronary syndrome (ACS) patients treated with drug eluting stents (DESs). METHODS: In this post-hoc analysis of the TICO trial, HBR was defined by 2 approaches: meeting Academic Research Consortium for HBR (ARC-HBR) criteria or Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent DAPT (PRECISE-DAPT) score ≥25. The primary outcome was a 3-12 months net adverse clinical event (composite of major bleeding and adverse cardiac and cerebrovascular events). RESULTS: Of the 2,980 patients without adverse events during the first 3 months after DES implantation, 453 (15.2%) were HBR by ARC-HBR criteria and 504 (16.9%) were HBR by PRECISE-DAPT score. The primary outcome rate was higher in HBR versus non-HBR patients (by ARC-HBR criteria: hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.76-4.69; p<0.001; by PRECISE-DAPT score: HR, 3.09; 95% CI, 1.92-4.98; p<0.001). Ticagrelor monotherapy after 3-month DAPT was associated with lower primary outcome rate than ticagrelor-based 12-month DAPT regardless of HBR by ARC-HBR criteria, with similar magnitudes of therapy effect for HBR and non-HBR patients (p-interaction=0.400). Results were consistent by PRECISE-DAPT score (p-interaction=0.178). CONCLUSIONS: In ACS patients treated with DESs, ticagrelor monotherapy after 3-month DAPT was associated with lower rate of adverse clinical outcomes regardless of HBR, with similar magnitudes of therapy effect between HBR and non-HBR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02494895.

Association of proteinuria and incident atrial fibrillation in patients with diabetes mellitus: a population-based senior cohort study.

Diabetes mellitus (DM) is considered an independent risk factor for atrial fibrillation (AF). The excess risk in relation to the presence of proteinuria has not been well elucidated. Our aim was to determine the association between the incidence of AF and proteinuria in diabetic population. A total of 240,499 individuals aged ≥ 60 years from the Korea National Health Insurance Service-Senior cohort from 2004 to 2014 were included. 4.2% of individuals with DM and 3.7% of controls were diagnosed with AF during a median follow-up period of 7.2 years. Amongst controls (participants without proteinuria and DM), DM only, proteinuria only, and DM with proteinuria groups, the crude incidences of AF were 0.58, 0.70, 0.96, 1.24 per 100 person-years respectively. Compared with controls, the weighted risk of AF was increased by 11% (hazard ratio = 1.11, 95% confidence interval = 1.02-1.20, P = .001), 48% (hazard ratio = 1.48, 95% confidence interval = 1.30-1.69, P < .001), and 66% (hazard ratio = 1.66, 95% confidence interval = 1.26-2.18, P < .001) in the DM only, proteinuria only, and DM with proteinuria groups, respectively (P for trend < .001). Degree of proteinuria in diabetic patients was associated with a significantly higher rate of incident AF in dose dependent manner. Thus, assessing proteinuria by a simple urine dipstick test could provide a useful adjunct to risk assessment for AF in elderly population with DM.

Clinical Characteristics and Predictors of In-Hospital Mortality in Patients With Cardiogenic Shock: Results From the RESCUE Registry.

BACKGROUND: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS. METHODS: The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality. RESULTS: In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and nonischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intraaortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multivariable analysis, age ≥70years (odds ratio [OR], 2.73 [95% CI, 1.89-3.94], P<0.001), body mass index <25 kg/m2 (OR, 1.52 [95% CI, 1.08-2.16], P=0.017), cardiac arrest at presentation (OR, 2.16 [95% CI, 1.44-3.23], P<0.001), vasoactive-inotrope score >80 (OR, 3.55 [95% CI, 2.54-4.95], P<0.001), requiring continuous renal replacement therapy (OR, 4.14 [95% CI, 2.88-5.95], P<0.001), mechanical ventilator (OR, 3.17 [95% CI, 2.16-4.63], P<0.001), intraaortic balloon pump (OR, 1.55 [95% CI, 1.07-2.24], P=0.020), and extracorporeal membrane oxygenator (OR, 1.85 [95% CI, 1.25-2.76], P=0.002) were independent predictors for in-hospital mortality. CONCLUSIONS: The in-hospital mortality of patients with CS remains high despite the high utilization of mechanical circulatory support. Age, low body mass index, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure requiring various support devices were poor prognostic factors for in-hospital mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Consensus Decision-Making for the Management of Antiplatelet Therapy before Non-Cardiac Surgery in Patients Who Underwent Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents: A Cohort Study.

Background Although antiplatelet therapy (APT) has been recommended to balance ischemic-bleeding risks, it has been left to an individualized decision-making based on physicians' perspectives before non-cardiac surgery. The study aimed to assess the advantages of a consensus among physicians, surgeons, and anesthesiologists on continuation and regimen of preoperative APT in patients with coronary drug-eluting stents. Methods and Results A total of 3582 adult patients undergoing non-cardiac surgery after percutaneous coronary intervention with second-generation stents was retrospectively included from a multicenter cohort. Physicians determined whether APT should be continued or discontinued for a recommended period before non-cardiac surgery. There were 3103 patients who complied with a consensus decision. Arbitrary APT, not based on a consensus decision, was associated with urgent surgery, high bleeding risk of surgery, female sex, and dual APT at the time of preoperative evaluation. Arbitrary APT independently increased the net clinical adverse event (adjusted odds ratio [ORadj], 1.98; 95% CI, 1.98-3.11), major adverse cardiac event (ORadj, 3.11; 95% CI, 1.31-7.34), and major bleeding (ORadj, 2.34; 95% CI, 1.45-3.76) risks. The association was consistently noted, irrespective of the surgical risks, recommendations, and practice on discontinuation of APT. Conclusions Most patients were treated in agreement with a consensus decision about preoperative APT based on a referral system among physicians, surgeons, and anesthesiologists. The risk of perioperative adverse events increased if complying with a consensus decision was failed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03908463.

Ticagrelor Monotherapy Versus Ticagrelor With Aspirin in Patients With ST-Segment Elevation Myocardial Infarction.

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).

Differential Prognostic Implications of Vasoactive Inotropic Score for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock According to Use of Mechanical Circulatory Support.

OBJECTIVES: To identify whether the prognostic implications of Vasoactive Inotropic Score according to use of mechanical circulatory support differ in the treatment of acute myocardial infarction complicated by cardiogenic shock. DESIGN: A multicenter retrospective and prospective observational cohort study. SETTING/PATIENT: The REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy registry includes 1,247 patients with cardiogenic shock from 12 centers in Korea. A total of 836 patients with acute myocardial infarction complicated by cardiogenic shock were finally selected, and the study population was stratified by quartiles of Vasoactive Inotropic Score (< 10, 10-30, 30-90, and > 90) for the present study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was in-hospital mortality and secondary endpoint was follow-up mortality. Among the study population, 326 patients (39.0%) received medical treatment alone, 218 (26.1%) received intra-aortic balloon pump, and 292 (34.9%) received extracorporeal membrane oxygenation. In-hospital mortality occurred in 305 patients (36.5%) and was significantly higher in patients with higher Vasoactive Inotropic Score (15.6%, 20.8%, 40.2%, and 67.3%, for < 10, 10-30, 30-90, and > 90; p < 0.001). Vasoactive Inotropic Score showed better ability to predict in-hospital mortality in acute myocardial infarction patients with cardiogenic shock who received medical treatment alone (area under the curve: 0.797; 95% CI, 0.728-0.865) than in those who received intra-aortic balloon pump (area under the curve, 0.704; 95% CI, 0.625-0.783) or extracorporeal membrane oxygenation (area under the curve, 0.644; 95% CI, 0.580-0.709). The best cutoff value of Vasoactive Inotropic Score for the prediction of in-hospital mortality also differed according to the use of mechanical circulatory support (16.5, 40.1, and 84.0 for medical treatment alone, intra-aortic balloon pump, and extracorporeal membrane oxygenation, respectively). There was a significant interaction between Vasoactive Inotropic Score as a continuous value and the use of mechanical circulatory support including intra-aortic balloon pump (interaction-p = 0.006) and extracorporeal membrane oxygenation (interaction-p < 0.001) for all-cause mortality during follow-up. CONCLUSIONS: High Vasoactive Inotropic Score was associated with significantly higher in-hospital and follow-up mortality in patients with acute myocardial infarction complicated by cardiogenic shock. The predictive value of Vasoactive Inotropic Score for mortality was significantly higher in acute myocardial infarction patients with cardiogenic shock treated by medical treatment alone than in those treated by mechanical circulatory support such as intra-aortic balloon pump or extracorporeal membrane oxygenation.

Optimal Duration for Dual Antiplatelet Therapy After Left Main Coronary Artery Stenting.

BACKGROUND: Coronary interventions using drug-eluting stents (DESs) of left main coronary artery (LMCA) lesions have shown favorable clinical outcomes. However, duration of dual antiplatelet therapy (DAPT) after LMCA interventions has not yet been investigated.Methods and Results:From a multicenter Korean Multicenter Angioplasty Team (KOMATE) registry, 1,004 patients who received DES implantations for LMCA lesions and did not experience major adverse cardiovascular events (including major bleeding) for 1 year after coronary intervention were analyzed. Patients were divided into 2 groups; DAPT ≤12 (n=503) and >12 months (n=501). The primary endpoint was number of net clinical adverse events (NACEs), composite of cardiac deaths, myocardial infarctions, stent thrombosis and major bleeding events. During a 4.5-year follow-up period after LMCA interventions, the DAPT >12 months group showed a lower NACE rate than the DAPT ≤12 months group (adjusted-HR 0.53 [0.29-0.99], P=0.045). For patients who maintained DAPT >12 months, rate of cardiac deaths, myocardial infarctions, and stent thrombosis events were lower than in patients who had DAPT ≤12 months (adjusted-HR 0.35 [0.17-0.73], P=0.005) without increased major bleeding (P=0.402). CONCLUSIONS: For patients who can continue DAPT without major bleeding events, prolonged DAPT (>12 months) after LMCA stenting demonstrated better long-term efficacy outcomes than DAPT ≤12 months with comparable safety.

Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial.

Importance: Discontinuing aspirin after short-term dual antiplatelet therapy (DAPT) was evaluated as a bleeding reduction strategy. However, the strategy of ticagrelor monotherapy has not been exclusively evaluated in patients with acute coronary syndromes (ACS). Objective: To determine whether switching to ticagrelor monotherapy after 3 months of DAPT reduces net adverse clinical events compared with ticagrelor-based 12-month DAPT in patients with ACS treated with drug-eluting stents. Design, Setting, and Participants: A randomized multicenter trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea. Follow-up was completed in October 2019. Interventions: Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529). Main Outcomes and Measures: The primary outcome was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization). Prespecified secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events. Results: Among 3056 patients who were randomized (mean age, 61 years; 628 women [20%]; 36% ST-elevation myocardial infarction), 2978 patients (97.4%) completed the trial. The primary outcome occurred in 59 patients (3.9%) receiving ticagrelor monotherapy after 3-month DAPT and in 89 patients (5.9%) receiving ticagrelor-based 12-month DAPT (absolute difference, -1.98% [95% CI, -3.50% to -0.45%]; hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.92]; P = .01). Of 10 prespecified secondary outcomes, 8 showed no significant difference. Major bleeding occurred in 1.7% of patients with ticagrelor monotherapy after 3-month DAPT and in 3.0% of patients with ticagrelor-based 12-month DAPT (HR, 0.56 [95% CI, 0.34 to 0.91]; P = .02). The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the ticagrelor monotherapy after 3-month DAPT group (2.3%) vs the ticagrelor-based 12-month DAPT group (3.4%) (HR, 0.69 [95% CI, 0.45 to 1.06]; P = .09). Conclusions and Relevance: Among patients with acute coronary syndromes treated with drug-eluting stents, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year. The study population and lower than expected event rates should be considered in interpreting the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02494895.

Resuscitative endovascular balloon occlusion of the aorta for retroperitoneal hemorrhage and shock after ipsilateral antegrade angioplasty with vascular closure device.

Percutaneous intervention is widely used to treat peripheral vascular disease. Ipsilateral antegrade femoral arterial access for femoropopliteal disease provides a mechanical advantage with regard to wire and stent control; however, it is associated with vascular complications and significant morbidity and mortality secondary to retroperitoneal hemorrhage from a high puncture site or vascular closure device (VCD) failure. Currently, resuscitative endovascular balloon occlusion of the aorta (REBOA) is performed as damage control surgery in patients with non-compressible torso hemorrhage. We describe a patient with hemorrhagic shock secondary to VCD failure, who was successfully treated by REBOA as damage control surgery. To our knowledge, this is the first reported case in the English literature of successful REBOA in a patient with hemorrhagic shock secondary to VCD failure.

Patterns of Antiplatelet Therapy During Noncardiac Surgery in Patients With Second-Generation Drug-Eluting Stents.

Background Continuing antiplatelet therapy (APT) has been generally recommended during noncardiac surgery, but it is uncertain if preoperative discontinuation of APT has been avoided or harmful in patients with second-generation drug-eluting coronary stents. Methods and Results Patients undergoing noncardiac surgery after second-generation drug-eluting coronary stent implantation were assessed in a multicenter cohort in Korea. Net adverse clinical events within 30 days postoperatively, defined as all-cause death, major adverse cardiac events, and major bleeding, were evaluated. Of 3582 eligible patients, 49% patients discontinued APT during noncardiac surgery. The incidence of net adverse clinical events was comparable between patients with continuation versus discontinuation (4.1% versus 3.4%; P=0.257) of APT during noncardiac surgery. Perioperative discontinuation of APT did not impact on net adverse clinical events (adjusted hazard ratio [HR], 1.00; 95% CI, 0.69-1.44; P=0.995). In subgroup analysis, patients undergoing intra-abdominal surgery were exposed to less risk of major bleeding by discontinuing APT (adjusted HR, 0.26; 95% CI, 0.08-0.91; P=0.035). Prolonged discontinuation of APT for ≥9 days was associated with higher risk of a major adverse cardiac event compared with continuing APT (adjusted HR, 3.38; 95% CI, 1.36-8.38; P=0.009). Conclusions APT was discontinued preoperatively in almost half of patients with second-generation drug-eluting coronary stents. Our explorative analysis showed that there was no significant impact of discontinuing APT on the risk of perioperative adverse events except that discontinuing APT may be associated with decreased hemorrhagic risk in patients undergoing intra-abdominal surgery. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03908463.

Mitochondrial Quality Control in the Heart: New Drug Targets for Cardiovascular Disease.

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.