Korean Multicenter Registry of ELUVIA Stent for Femoropopliteal Artery Disease: K-ELUVIA Registry.

BACKGROUND AND OBJECTIVES: The K-ELUVIA study aimed to investigate the clinical effectiveness and safety of Eluvia™, a polymer-coated, paclitaxel-eluting stent, for femoropopliteal artery disease using data from a prospective Korean multicenter registry. METHODS: A total of 105 patients with femoropopliteal artery disease who received endovascular treatment (EVT) with Eluvia™ stents at 7 Korean sites were enrolled in a prospective cohort and followed for 2 years. The primary endpoint was the 2-year clinical patency. The secondary endpoint was 2-year freedom from clinically driven target lesion revascularization (TLR). RESULTS: Mean patient age was 68.2±10.4 years, and most patients (82.7%) were male. Mean lesion length was 168.3±117.6 mm. Chronic total occlusion was found in 57.7% of patients. Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) type C or D lesions were present in 46.1% of patients. Procedural success was achieved in 99.0% of patients. The clinical patency rate was 84.4% at 1 year after EVT and 76.3% at 2 years post-EVT. The freedom from TLR rate was 89.1% at 1 year after EVT and 79.1% at 2 years post-EVT. Chronic total occlusion (hazard ratio [HR], 3.53; 95% confidence interval [CI], 1.08-11.67; p=0.039) and smaller mean stent diameter (HR, 0.40; 95% CI, 0.16-0.98; p=0.044) were identified as independent predictors of loss of clinical patency at 2 years. CONCLUSIONS: The K-ELUVIA study demonstrated favorable 2-year clinical effectiveness and safety outcomes of Eluvia stent for femoropopliteal artery lesions in real-world practice.

Cardiogenic shock complicating acute myocardial infarction and multivessel disease: revascularization strategy according to ischemic territory.

INTRODUCTION AND OBJECTIVES: The association of revascularization strategy with clinical outcomes according to the ischemic territory of nonculprit lesion has not been documented in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). This study aimed to compare outcomes between culprit-only and immediate multivessel percutaneous coronary intervention (PCI) according to ischemic territory in patients with AMI-CS. METHODS: A total of 536 patients with AMI-CS and multivessel disease from the SMART-RESCUE registry were categorized according to ischemic territory (nonculprit left main/proximal left anterior descending artery [LM/pLAD] vs culprit LM/pLAD vs no LM/pLAD). The primary outcome was a patient-oriented composite endpoint (POCE) consisting of all-cause death, myocardial infarction, rehospitalization due to heart failure, or repeat revascularization at 1 year. RESULTS: Among the total population, 108 patients had nonculprit LM/pLAD, 228 patients had culprit LM/pLAD, and 200 patients had no LM/pLAD, with the risk of POCE being higher in patients with large ischemic territory lesions (53.6% vs 53.4% vs 39.6%; P = .02). Multivessel PCI was associated with a significantly lower risk of POCE compared with culprit-only PCI in patients with nonculprit LM/pLAD (40.7% vs 66.9%; HR, 0.52; 95%CI, 0.29-0.91; P=.02), but not in those with culprit LM/pLAD (P=.46) or no LM/pLAD (P=.47). A significant interaction existed between revascularization strategy and large nonculprit ischemic territory (P=.03). CONCLUSIONS: Large ischemic territory involvement was associated with worse clinical outcomes in patients with AMI-CS and multivessel disease. Immediate multivessel PCI might improve clinical outcomes in patients with a large nonculprit ischemic burden.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent: The SHARE Randomized Clinical Trial.

Importance: P2Y12 inhibitor monotherapy after dual antiplatelet therapy (DAPT; a P2Y12 inhibitor plus aspirin) for a brief duration has recently emerged as an attractive alternative for patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent. Objective: To investigate whether P2Y12 inhibitor monotherapy after 3 months of DAPT was noninferior to 12 months of DAPT following PCI with a drug-eluting stent. Design, Setting, and Participants: The Short-Term Dual Antiplatelet Therapy After Deployment of Bioabsorbable Polymer Everolimus-Eluting Stent (SHARE) open-label, noninferiority randomized clinical trial was conducted from December 15, 2017, through December 14, 2020. Final 1-year clinical follow-up was completed in January 2022. This study was a multicenter trial that was conducted at 20 hospitals in South Korea. Patients who underwent successful PCI with bioabsorbable polymer everolimus-eluting stents were enrolled. Interventions: Patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (n = 694) or 12 months of DAPT (n = 693). Main Outcomes and Measures: The primary outcome was a net adverse clinical event, a composite of major bleeding (based on Bleeding Academic Research Consortium type 3 or type 5 bleeding) and major adverse cardiac and cerebrovascular events (cardiac death, myocardial infarction, stent thrombosis, stroke, or ischemia-driven target lesion revascularization) between 3 and 12 months after the index PCI. The major secondary outcomes were major adverse cardiac and cerebrovascular events and major bleeding. The noninferiority margin was 3.0%. Results: Of the total 1452 eligible patients, 65 patients were excluded before the 3-month follow-up, and 1387 patients (mean [SD] age, 63.0 [10.7] years; 1055 men [76.1%]) were assigned to P2Y12 inhibitor monotherapy (n = 694) or DAPT (n = 693). Between 3 and 12 months of follow-up, the primary outcome (using Kaplan-Meier estimates) occurred in 9 patients (1.7%) in the P2Y12 inhibitor monotherapy group and in 16 patients (2.6%) in the DAPT group (absolute difference, -0.93 [1-sided 95% CI, -2.64 to 0.77] percentage points; P < .001 for noninferiority). For the major secondary outcomes (using Kaplan-Meier estimates), major adverse cardiac and cerebrovascular events occurred in 8 patients (1.5%) in the P2Y12 inhibitor monotherapy group and in 12 patients (2.0%) in the DAPT group (absolute difference, -0.49 [95% CI, -2.07 to 1.09] percentage points; P = .54). Major bleeding occurred in 1 patient (0.2%) in the P2Y12 inhibitor monotherapy group and in 5 patients (0.8%) in the DAPT group (absolute difference, -0.60 [95% CI, -1.33 to 0.12] percentage points; P = .10). Conclusions and Relevance: In patients with coronary artery disease undergoing PCI with the latest generation of drug-eluting stents, P2Y12 inhibitor monotherapy after 3-month DAPT was not inferior to 12-month DAPT for net adverse clinical events. Considering the study population and lower-than-expected event rates, further research is required in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT03447379.

Associations of combined polygenic risk score and glycemic status with atrial fibrillation, coronary artery disease and ischemic stroke.

BACKGROUND: It is unknown whether high hemoglobin A1c (HbA1c) is associated with increases in the risk of cardiovascular disease among individuals with elevated genetic susceptibility. We aimed to investigate the association between HbA1c and atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke according to the polygenic risk score (PRS). METHODS: The UK Biobank cohort included 502,442 participants aged 40-70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. This study included 305,605 unrelated individuals with available PRS and assessed new-onset AF, CAD, and ischemic stroke. The participants were divided into tertiles based on the validated PRS for each outcome. Within each PRS tertiles, the risks of incident events associated with HbA1c levels were investigated and compared with HbA1c < 5.7% and low PRS. Data were analyzed from November 2022 to May 2023. RESULTS: Of 305,605 individuals, 161,605 (52.9%) were female, and the mean (SD) age was 56.6 (8.1) years. During a median follow-up of 11.9 (interquartile range 11.1-12.6) years, the incidences of AF, CAD, and ischemic stroke were 4.6, 2.9 and 1.1 per 100 person-years, respectively. Compared to individuals with HbA1c < 5.7% and low PRS, individuals with HbA1c ≥ 6.5% and high PRS had a 2.67-times higher risk for AF (hazard ratio [HR], 2.67; 95% confidence interval (CI), 2.43-2.94), 5.71-times higher risk for CAD (HR, 5.71; 95% CI, 5.14-6.33) and 2.94-times higher risk for ischemic stroke (HR, 2.94; 95% CI, 2.47-3.50). In the restricted cubic spline models, while a U-shaped trend was observed between HbA1c and the risk of AF, dose-dependent increases were observed between HbA1c and the risk of CAD and ischemic stroke regardless PRS tertile. CONCLUSIONS: Our results suggest that the nature of the dose-dependent relationship between HbA1c levels and cardiovascular disease in individuals with different PRS is outcome-specific. This adds to the evidence that PRS may play a role together with glycemic status in the development of cardiovascular disease.

Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial.

BACKGROUND: Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome. METHODS: In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point. RESULTS: Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment-elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12-25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37-0.80]; P<0.001 for noninferiority; P=0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20-0.61]; P<0.001). CONCLUSIONS: This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non-high-risk patients, should be considered in interpreting the trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651.

Influence of early dose reduction of ticagrelor on clinical outcomes following percutaneous coronary intervention for complex lesions.

Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk.

Culprit-Only Versus Immediate Multivessel Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction Complicating Advanced Cardiogenic Shock Requiring Venoarterial-Extracorporeal Membrane Oxygenation.

Background Despite the benefit of culprit-only percutaneous coronary intervention (PCI) in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multi-vessel PCI in Cardiogenic Shock) trial, the optimal revascularization strategy for refractory cardiogenic shock (CS) requiring mechanical circulatory support devices remains controversial. This study aimed to compare clinical outcomes between the culprit-only and immediate multivessel PCI strategies in patients with acute myocardial infarction complicated by CS who underwent venoarterial-extracorporeal membrane oxygenation before revascularization. Methods and Results This study included patient-pooled data from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Devices for Korean Patients With Cardiogenic Shock) and SMC-ECMO (Samsung Medical Center-Extracorporeal Membrane Oxygenation) registries. A total of 315 patients with acute myocardial infarction with multivessel disease who underwent venoarterial-extracorporeal membrane oxygenation before revascularization attributable to refractory CS were included in this analysis. The study population was classified into culprit-only versus immediate multivessel PCI according to nonculprit lesion treatment strategies. The primary end point was 30-day mortality or renal-replacement therapy, and the key secondary end point was 12-month follow-up mortality. Among the study population, 175 (55.6%) underwent culprit-only PCI and 140 (44.4%) underwent immediate multivessel PCI. Compared with culprit-only PCI, immediate multivessel PCI was associated with significantly lower risks of 30-day mortality or renal-replacement therapy (68.0% versus 54.3%; P=0.018) and all-cause mortality during 12 months of follow-up (59.5% versus 47.5%; hazard ratio [HR], 0.689 [95% CI, 0.506-0.939]; P=0.018) in patients with acute myocardial infarction and CS who underwent venoarterial-extracorporeal membrane oxygenation before revascularization. These results were also consistent in the 99 pairs of propensity score-matched population (60.6% versus 43.6%; HR, 0.622 [95% CI, 0.420-0.922]; P=0.018). Conclusions Among patients with acute myocardial infarction with multivessel disease complicated by advanced CS requiring venoarterial-extracorporeal membrane oxygenation before revascularization, immediate multivessel PCI was associated with lower incidences of 30-day mortality or renal replacement therapy and 12-month follow-up mortality, compared with culprit-only PCI. Registration Information clinicaltrials.gov. Identifier: NCT02985008.

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.

A randomized, double-blind, multicenter, phase III study on the efficacy and safety of a combination treatment involving fimasartan, amlodipine, rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy.

BACKGROUND: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. METHODS: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. RESULTS: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions. CONCLUSIONS: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. TRIAL REGISTRATION: NCT03156842, Registered 17 May 2017.

Comparison of 6-Month and Prolonged Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with Biodegradable Polymer Everolimus-Eluting Stent.

Background: The optimal duration of dual antiplatelet therapy (DAPT) after biodegradable-polymer (BP) everolimus-eluting stent (EES) implantation remains uncertain. Methods: This study analyzed 793 patients who underwent percutaneous coronary intervention (PCI) with BP-EES in 10 cardiovascular centers in Korea between July 2016 and January 2018. Using the prescription data at 6 months post-PCI, we divided these patients into two groups, namely, short-DAPT and prolonged-DAPT groups, which underwent DAPT for 6 and > 6 months of PCI, respectively. The primary endpoint, which included mortality, myocardial infarction, or target-vessel revascularization at 2 years, was compared by propensity score (PS) matching between the two groups. Results: Out of the 793 patients, 283 matched pairs were identified by PS matching. Out of this matched population, 405 (71.6%) patients had an acute coronary syndrome. The primary endpoint did not differ in 2 years between the short-DAPT and prolonged-DAPT groups (7.5% vs. 8.3%; hazard ratio, 0.87; 95% confidential interval, 0.47-1.60; P = 0.648). Likewise, no difference was found regarding mortality, cardiac mortality, myocardial infarction, target-lesion failure, target-vessel failure, and bleeding events defined by the Bleeding Academic Research Consortium and Thrombolysis In the Myocardial Infarction classification. Meanwhile, one patient in the short-DAPT group had definite stent thrombosis at 364 days post-PCI. Subgroup analysis showed that several anatomical and procedural factors were not significantly related to DAPT duration. Most patients (77.4%) in both groups were prescribed clopidogrel at discharge. Conclusions: In real-world patients undergoing PCI with BP-EES, the ischemic and bleeding endpoints demonstrated no difference between 6-month and prolonged (>6 months) DAPT.

Effects of high-intensity statin combined with telmisartan versus amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease patients with impaired fasting glucose: A randomized multicenter trial.

BACKGROUND: There is lacking evidence that telmisartan can improve insulin resistance in patients on high-intensity statins. This study compared the effects of telmisartan and amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease (ASCVD) patients with impaired fasting glucose (IFG) requiring high-intensity rosuvastatin therapy. METHODS: Ninety-nine patients were randomly assigned to 2 groups [telmisartan-statin group (n=48) and amlodipine-statin group (n=51)] as add-on therapy to high-intensity rosuvastatin therapy (20 mg). The primary endpoint was to assess insulin resistance using the homeostatic model assessment (HOMA-IR) value at week 24. The secondary endpoint was the change in glucose metabolism indices from baseline to week 24. RESULTS: The HOMA-IR at week 24 (2.4 [interquartile range, 1.8-3.8] versus 2.7 [1.7-3.7]; P = .809) and changes in the HOMA-IR from baseline to week 24 (-7.0 [-29.0 to 21.0] versus -5.5 [-53.3 to 27.3]; P = .539) were not significantly different between 2 groups. However, the fasting glucose level at week 24 was significantly lower in the telmisartan-statin group than in the amlodipine-statin group (107.7 ± 13.4 mg/dL versus 113.3 ± 12.4 mg/dL; P = .039) and significantly decreased in the telmisartan-statin group (-3.2 ± 8.6% versus 3.8 ± 13.2%; P = .003). The proportion of patients with fasting glucose ≥100 mg/dL (71.1% versus 89.6%; P = .047) or new-onset diabetes mellitus (12.5% versus 31.4%, P = .044) at week 24 was also significantly lower in the telmisartan-statin group than in the amlodipine-statin group. CONCLUSION: In comparison to amlodipine, telmisartan did not decrease the HOMA-IR. However, telmisartan preserved insulin secretion, led to a regression from IFG to euglycemia and prevented new-onset diabetes mellitus in ASCVD patients with IFG requiring high-intensity statins.

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.

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.

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.

Effects of Fixed-dose Combination of Low-intensity Rosuvastatin and Ezetimibe Versus Moderate-intensity Rosuvastatin Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia: A Randomized, Double-blind, Multicenter, Phase III Study.

PURPOSE: We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. FINDINGS: Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p<0.0001), R2.5 group (-32.6±15.1%, p<0.0001), and R5 group (-38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups. IMPLICATIONS: Fixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349.

Relationship between health-related quality of life and blood pressure control in patients with uncontrolled hypertension.

We sought to investigate the psychosocial characteristics of patients with uncontrolled hypertension and examine factors that influence blood pressure (BP) control. A total of 1011 patients with uncontrolled hypertension were enrolled in 13 tertiary hospitals. Uncontrolled hypertension was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg despite on antihypertensive therapy. Socio-demographics, anthropometrics, behavioral risk factors, medication pattern, adherence, and measures of health-related quality of life (HRQoL; EuroQol 5D visual analog scale [EQ-5D VAS]) were assessed at baseline and during follow-up visits (3 and 6 months). Patients were divided into 2 groups based on BP control status at 6 months (controlled group [n = 532] vs uncontrolled group [n = 367]). There were no differences in clinical characteristics except the proportion of smokers and baseline BP between patients with controlled BP and uncontrolled BP. At 6 months, the adherence of antihypertensive medication did not differ between the groups but the proportion of combination therapy with ≥3 antihypertensives was significantly higher in patients with uncontrolled BP. EQ-5D VAS at follow-up was significantly lower in patients with uncontrolled BP despite similar baseline values. Multivariate logistic regression analysis revealed that EQ-5D VAS at follow-up significantly correlated with BP control. Patients with worse HRQoL had higher Charlson Comorbidity Index and higher proportion of taking ≥3 antihypertensives, but medication adherence was similar to those with better HRQoL. These findings suggest that along with pharmacologic intervention of hypertension, management of comorbid conditions or psychological support might be helpful for optimizing BP control in patients with uncontrolled hypertension.

Determinants and Clinical Outcomes of Extended Dual Antiplatelet Therapy over 3 Years after Drug-Eluting Stent Implantation: A Retrospective Analysis.

PURPOSE: Although current guidelines recommend the administration of dual antiplatelet therapy (DAPT) for up to 12 months after the implantation of a drug-eluting stent (DES), extended DAPT is frequently used in real-world practice. MATERIALS AND METHODS: From the Korean Multicenter Angioplasty Team registry, we identified a total of 1414 patients who used DAPT for >3 years after DES implantation (extended-DAPT group) and conducted a landmark analysis at 36 months after the index procedure. We evaluated the determinants for and long-term outcomes of extended DAPT and compared the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stent thrombosis, and stroke, between the extended-DAPT group and the guideline-DAPT group [DAPT <1 year after DES implantation (n=1273)]. RESULTS: Multivariate analysis indicated the occurrence of acute coronary syndrome as the most significant clinical determinant of the use of extended DAPT. Bifurcation, stent diameter ≤3.0 mm, total stented length ≥28 mm, and use of first-generation DESs were also significant angiographic and procedural determinants. MACCE rates were similar between the extended-DAPT group and the guideline-DAPT group in crude analysis [hazard ratio (HR), 1.08; 95% confidence interval (CI), 0.69-1.68; p=0.739] and after propensity matching (HR, 1.22; 95% CI, 0.72-2.07; p=0.453). Major bleeding rates were comparable between the two groups. CONCLUSION: In patients undergoing percutaneous coronary intervention, indefinite use of DAPT does not show superior outcomes to those of guideline-DAPT. Major bleeding rates are also similar.