Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation.

INTRODUCTION: Risk factors of embolic stroke (ES) after atrial fibrillation (AF) ablation have not been fully elucidated especially among the Asian subjects, particularly regarding epicardial adipose tissue (EAT) in cardiac imaging. We aimed to assess the incidence of ES during a long-term follow-up period after AF ablation and to identify the risk factors associated with postablation ES, specifically focusing on EAT. METHODS AND RESULTS: We enrolled patients who experienced postablation ES and control subjects from a consortium of AF ablation registries from three institutes in Korea. EAT was assessed using multislice computed tomography before AF ablation. A total of 3464 patients who underwent AF ablation were recruited and followed-up. During a follow-up of 47.2 ± 36.4 months, ES occurred in 47 patients (1.36%) with a CHA2 DS2 -VASc score of 1.48 ± 1.39 and the overall annual incidence of ES was 0.34%. Compared with the control group (n = 190), the ES group showed significantly higher prior thromboembolism (TE) and AF recurrence rates, larger left atrium size, lower creatinine clearance rate (CCr), and greater total and peri-atrial EAT volume. Multivariate regression analysis demonstrated larger peri-atrial EAT volume (hazards ratio, 1.065; 95% confidence interval, 1.005-1.128), in addition to a prior history of TE and lower CCr, was independently associated with postablation ES. When a cut-off value of peri-atrial EAT volume of ≥20.15 mL was applied, patients with smaller peri-atrial EAT volume showed significantly higher ES-free survival. CONCLUSION: Larger peri-atrial EAT volume, in addition to prior TE and lower CCr, was independently associated with postablation ES regardless of AF recurrence and CHA2 DS2 -VASc score. (ClinicalTrials.gov number, NCT03479073).

Fractional Flow Reserve and Cardiac Events in Coronary Artery Disease: Data From a Prospective IRIS-FFR Registry (Interventional Cardiology Research Incooperation Society Fractional Flow Reserve).

BACKGROUND: We evaluated the prognosis of deferred and revascularized coronary stenoses after fractional flow reserve (FFR) measurement to assess its revascularization threshold in clinical practice. METHODS: The IRIS-FFR registry (Interventional Cardiology Research In-cooperation Society Fractional Flow Reserve) prospectively enrolled 5846 patients with ≥1coronary lesion with FFR measurement. Revascularization was deferred in 6468 lesions and performed in 2165 lesions after FFR assessment. The primary end point was major adverse cardiac events (cardiac death, myocardial infarction, and repeat revascularization) at a median follow-up of 1.9 years and analyzed on a per-lesion basis. A marginal Cox model accounted for correlated data in patients with multiple lesions, and a model to predict per-lesion outcomes was adjusted for confounding factors. RESULTS: For deferred lesions, the risk of major adverse cardiac events demonstrated a significant, inverse relationship with FFR (adjusted hazard ratio, 1.06; 95% confidence interval, 1.05-1.08; P<0.001). However, this relationship was not observed in revascularized lesions (adjusted hazard ratio, 1.00; 95% confidence interval, 0.98-1.02; P=0.70). For lesions with FFR ≥0.76, the risk of major adverse cardiac events was not significantly different between deferred and revascularized lesions. Conversely, in lesions with FFR ≤0.75, the risk of major adverse cardiac events was significantly lower in revascularized lesions than in deferred lesions (for FFR 0.71-0.75, adjusted hazard ratio, 0.47; 95% confidence interval, 0.24-0.89; P=0.021; for FFR ≤0.70, adjusted hazard ratio 0.47; 95% confidence interval, 0.26-0.84; P=0.012). CONCLUSIONS: This large, prospective registry showed that the FFR value was linearly associated with the risk of cardiac events in deferred lesions. In addition, revascularization for coronary artery stenosis with a low FFR (≤0.75) was associated with better outcomes than the deferral, whereas for a stenosis with a high FFR (≥0.76), medical treatment would be a reasonable and safe treatment strategy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01366404.

Treatment Strategies for Atrial Fibrillation With Left Ventricular Systolic Dysfunction　- Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) frequently coexists with heart failure (HF) with reduced ejection fraction (EF). This meta-analysis compared AF control strategies, that is, rhythm vs. rate, and catheter ablation (CA) vs. anti-arrhythmic drugs (AAD) in patients with AF combined with HF.Methods and Results:The MEDLINE, EMBASE, and CENTRAL databases were searched, and 13 articles from 11 randomized controlled trials with 5,256 patients were included in this meta-analysis. The outcomes were echocardiographic parameters (left ventricular EF, LVEF), left atrial (LA) size, and left ventricular end-systolic volume, LVESV), clinical outcomes (mortality, hospitalization, and thromboembolism), exercise capacity, and quality of life (QOL). In a random effects model, rhythm control was associated with higher LVEF, better exercise capacity, and better QOL than the rate control. When the 2 different rhythm control strategies were compared (CA vs. AAD), the CA group had significantly decreased LA size and LVESV, and improved LVEF and 6-min walk distance, but mortality, hospitalization, and thromboembolism rates were not different between the rhythm and rate control groups. CONCLUSIONS: In AF combined with HF, even though mortality, hospitalization and thromboembolism rates were similar, a rhythm control strategy was superior to rate control in terms of improvement in LVEF, exercise capacity, and QOL. In particular, the CA group was superior to the AAD group for reversal of cardiac remodeling.

Reverse Left Ventricular Remodelling in ST-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: Incidence, Predictors, and Impact on Outcome.

BACKGROUD: We investigated reverse left ventricular remodelling (r-LVR), defined as a reduction of >10% in left ventricular end-systolic volume (LVESV) during follow-up, in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: STEMI patients (n=1,237) undergoing PPCI with echocardiography at baseline and 6-month follow-up were classified into r-LVR (n=466) and no r-LVR groups (n=771). The primary outcome was composite major adverse cardiac events (MACE; all-cause death, myocardial infarction, any revascularisation). RESULTS: r-LVR occurred in 466 patients (37.7%) and was associated with maximum troponin, door-to-balloon time, direct arrival to PPCI-capable hospital, coronary disease extent, initial left ventricular ejection fraction (LVEF), and LVESV. After propensity score (PS)-matching, initial LVEF and LVESV remained significant. During a median 403-day follow-up, 2-year MACE occurred in 166 patients (13.4%); its frequency was similar between groups (entire cohort: 13.5% vs. 13.4%, p=0.247; PS-matched: 11.8% vs. 11.8%, p=0.987). Kaplan-Meier estimates showed that MACE-free survival was comparable between groups (entire cohort: 86.5% vs. 86.6%, log rank p=0.939; PS-matched: 88.2% vs. 88.2%, log rank p=0.867). In Cox proportional hazard analysis, r-LVR was not associated with MACE (entire cohort: hazard ratio [HR] 1.018, 95% confidential interval [CI] 0.675-1.534, p=0.934; PS-matched: HR 1.001, 95% CI 0.578-1.731, p=0.999). CONCLUSION: We identified independent predictors of r-LVR and showed that while r-LVR occurred in 38% of our patients, it was not associated with clinical outcomes.

Platelet reactivity and clinical outcomes in patients using CYP3A4-metabolized statins with clopidogrel in percutaneous coronary intervention.

Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel's anti-aggregatory effect on platelets. We aimed to assess the impact of concomitant CYP3A4-metabolized statin and clopidogrel use on antiplatelet activity and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We enrolled 1187 patients from the HOST-ASSURE trial with platelet reactivity unit (PRU) values at both baseline and 1 month. Patients were assigned to the CYP3A4-metabolized statin group (group A, n = 725) or non-CYP3A4-metabolized statin group (group B, n = 462) according to type of statin used. Co-primary outcomes were the differences between PRU at baseline and 1 month and the composite of cardiovascular death, recurrent myocardial infarction, stent thrombosis, revascularization, and cerebrovascular accident. We found that follow-up PRU values did not change in group A and decreased significantly in group B (mean difference: -15 ± 79, p < 0.001) in both the crude and matched cohorts. Patients with a high PRU value at baseline, irrespective of statin type, had a significant reduction in mean PRU difference (group A, -62 ± 78, p < 0.001; group B, -59 ± 69, p < 0.001) in both the crude and matched cohorts. The composite of clinical events did not differ between groups in either cohort. CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. However, they do not inhibit clopidogrel's antiplatelet effect in patients with high platelet reactivity or increase clinical events in patients following PCI.

Comparison of the axillary venous approach and subclavian venous approach for efficacy of permanent pacemaker implantation. 8-Year follow-up results.

BACKGROUND: Long-term data on lead complication rates are limited for both the axillary and subclavian venous approaches for permanent pacemaker implantation. METHODS AND RESULTS: We conducted a single-center, retrospective, nonrandomized comparison. We reviewed the patients who had consented to receiving a permanent pacemaker implant. A superficial landmark or radiographic contrast guiding was used for the axillary venous approach, whereas conventional landmarks were used for the subclavian venous approach. From January 1992 to December 2005, we analyzed 1,161 permanent pacemaker leads in 655 patients [subclavian venous approach (group I: 338 patients, 542 leads) and axillary venous approach (group II: 317 patients, 619 leads)]. Baseline characteristics of the patients did not differ. However, DDD-pacemakers and atrial leads were used more often in group II than in group I (94% vs. 62% and 49% vs. 40%, P<0.01). During the 8-year follow-up, lead complication rates were lower in group II (17 leads, 3%) than in group I (31 leads, 6%) (P=0.03), and group II had a better complication-free survival curve than group I with a 49% relative risk reduction in lead complication rates (hazard ratio =0.51; 95% confidence interval, 0.27-0.94; P=0.03). CONCLUSIONS: The axillary venous approach for permanent pacemaker implantation has better long-term efficacy and lower lead complication rates than the subclavian venous approach.

The effect of intracoronary administration of ergonovine on the contralateral coronary artery in a provocation test for the diagnosis of variant angina.

BACKGROUND: Little is known about the effects of selective intracoronary administration of ergonovine into a coronary artery on the artery on the other side. This study aimed to evaluate the effect of intracoronarily administered ergonovine on the contralateral coronary artery. SUBJECTS AND METHODS: From June 2011 to August 2013, coronary spasm provocation tests were performed in 85 consecutive patients using selective intracoronary administration of methylergometrine maleate (ER).The doses increased in a step-wise manner up to 60 µg for the left coronary artery (LCA) and up to 50 µg for the right coronary artery (RCA).The coronary artery diameters were measured and analysed by repeated-measures ANOVA. RESULTS: Twenty-four (28%) patients had a spasm-positive result. The mean diameter of the spasm segment in the contralateral artery decreased from 2.83 to 2.68 mm (5.1 ± 0.1% change, P < 0.001) in the negative spasm group and from 2.40 to 2.10 mm (11.1 ± 2.2% change, P = 0.001) in the positive spasm group. There were no serious procedure-related complications. CONCLUSIONS: Intracoronary administration of ER resulted in a statistically significant decrease of lumen diameter of the contralateral coronary artery. However, from the clinical perspective, the extent of the decrease was relatively small and the test may be conducted safely unless there is a significant coronary artery luminal narrowing.

Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. METHODS AND RESULTS: We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72-49.96; P=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60-2.47; P=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42-7.03; P=0.005) among diabetic patients. CONCLUSIONS: Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00698607.

Clinical outcome of unprotected left main coronary artery disease in patients with acute myocardial infarction.

The clinical outcome of patients with acute myocardial infarction (MI) with unprotected left main coronary artery (LMCA) stenosis is not fully understood. We sought to assess the outcomes of patients with acute MI who underwent percutaneous coronary intervention (PCI) for unprotected LMCA stenosis. A total of 587 patients enrolled in the Korea Acute Myocardial Infarction Registry with LMCA stenosis were analyzed. Patients with culprit LMCA had higher inhospital mortality than patients with non-culprit LMCA (16.0% versus 8.9%, P = 0.008), but had similar clinical outcomes during a 12-month follow-up. Compared to CABG, PCI using drug-eluting stents (DES) was more frequently performed with similar early and 12-month clinical outcomes. The efficacy of sirolimus-eluting stents, paclitaxel-eluting stents, and zotarolimus-eluting stents were comparable at 12-month clinical follow-up. Predictors of 12-month mortality included mechanical ventilation, cardiogenic shock, age > 65 years, and ejection fraction < 40%. Patients with acute MI and culprit LMCA have higher early mortality than patients with non-culprit LMCA. PCI with DES is frequently performed and the clinical outcome is similar between the 3 types of first-generation DES.

A Randomized, Multicenter, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Quadruple Combination of Amlodipine, Losartan, Rosuvastatin, and Ezetimibe in Patients with Concomitant Essential Hypertension and Dyslipidemia.

BACKGROUND: Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia. OBJECTIVE: We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia. METHODS: This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145 patients were randomized to receive A/L/R/E, A/L, or L/R/E. The primary endpoints were the average change in the low-density lipoprotein cholesterol (LDL-C) level in the A/L/R/E and A/L groups and the sitting systolic blood pressure (sitSBP) in the A/L/R/E and L/R/E groups. The numbers of patients with adverse drug reactions (ADRs) were compared as safety variables. RESULTS: The average percentage change in the LDL-C level as the least squares mean (LSM) from the baseline LDL-C level at the end of the 8-week treatment was - 59.0% in the A/L/R/E group and 0.2% in the A/L group (LSM difference - 59.2, 95% confidence interval [CI] - 68.1 to - 50.4; p < 0.0001). The average change in the sitSBP as the LSM was - 15.8 mmHg in the A/L/R/E group and -4.7 mmHg in the L/R/E group (LSM difference - 11.1, 95% CI - 16.8 to - 5.4; p = 0.0002). No ADRs occurred in the A/L/R/E group. CONCLUSIONS: A/L/R/E as an SPC could be an effective treatment for patients with hypertension and dyslipidemia without significant safety issues. CLINICAL TRIALS REGISTRATION: NCT04074551 (registered 30 August 2019).

Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study.

BACKGROUND: Treatment of critical limb ischemia (CLI) by bypass operation or percutaneous vascular intervention is occasionally difficult. The safety and efficacy of multiple intramuscular adipose tissue-derived mesenchymal stem cells (ATMSC) injections in CLI patients was determined in the study. METHODS AND RESULTS: The study included 15 male CLI patients with ischemic resting pain in 1 limb with/without non-healing ulcers and necrotic foot. ATMSC were isolated from adipose tissue of thromboangiitis obliterans (TAO) patients (B-ATMSC), diabetes patients (D-ATMSC), and healthy donors (control ATMSC). In a colony-forming unit assay, the stromal vascular fraction of TAO and diabetic patients yielded lesser colonies than that of healthy donors. D-ATMSC showed lower proliferation abilitythan B-ATMSC and control ATMSC, but they showed similar angiogenic factor expression with control ATMSC and B-ATMSC. Multiple intramuscular ATMSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSC implantation showed formation of numerous vascular collateral networks across affected arteries. CONCLUSIONS: Multiple intramuscular ATMSC injections might be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities.

Clinical outcomes of patients who received a lower dose of non-vitamin K antagonist oral anticoagulants for the medical management of acute pulmonary embolism.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are used to treat acute pulmonary embolism (PE). However, lower NOAC doses are often prescribed because of increased risk of NOAC complications. OBJECTIVE: We sought to determine the incidence and clinical outcomes of patients with acute provoked PE receiving lower NOAC doses. METHOD: 140 patients with acute PE with only NOACs used for medical management was enrolled and were followed up for 6 months. The composite primary endpoint was all-cause death, venous thromboembolism recurrence, and residual thrombus on follow-up computed tomography. RESULTS: Of the 140 patients, 99 (70.7%) received the standard NOAC dose and 41 (29.3%) received the lower dose. The crude incidences of the primary endpoint were 19 (19.2%) in patients who received the standard NOAC dose and 13 (31.7%) in those who received the lower dose. Compared with patients who received the standard dose, those who received the lower dose had no differences in the rate of primary endpoints (hazard ratio 1.140, 95% confidence interval 0.536-2.423, p = 0.733) during a median of 185 days. CONCLUSION: We found that up to 30% of patients received the lower dose of NOACs for acute PE in clinical practice. Clinical outcomes with appropriate underdoing of NOAC treated in acute PE might not increase compared to the standard NOAC doses.

Standard versus high loading doses of clopidogrel in Asian ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: insights from the Korea Acute Myocardial Infarction Registry.

BACKGROUND: The optimal loading dose of clopidogrel in Asian patients with ST-segment elevation myocardial infarction (STEMI) has not been fully investigated. We compared bleeding, vascular complications, and midterm outcomes of a 300-mg versus a 600-mg loading dose of clopidogrel in a large series of Korean patients with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 2,664 STEMI patients (age 61.96 ± 11.91 years, men 70.4%) who underwent primary PCI were enrolled in this study. The patients were divided into a standard loading dose group (300 mg; n = 1,447 patients) and a high loading dose group (600 mg; n = 1,217 patients). Bleeding and vascular complications, and in-hospital and clinical outcomes up to 12 months were compared between the 2 groups. RESULTS: In-hospital bleeding and vascular complications were similar between the 2 groups. There were no differences in bleeding and vascular complications and in 1- and 12-month clinical outcomes, including mortality, myocardial infarction, repeated PCI, and major adverse cardiac events, between the 2 groups. These findings were consistent even after the propensity score-matched analysis. CONCLUSIONS: The standard loading dose of clopidogrel may be as safe and similarly effective as the high loading dose in Asian STEMI patients undergoing primary PCI.

Comparison of paclitaxel-, sirolimus-, and zotarolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction and metabolic syndrome.

BACKGROUND: The purpose of the present study was to compare the efficacy and safety of paclitaxel-eluting stent (PES), sirolimus-eluting stent (SES), and zotarolimus-eluting stent (ZES) in primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI) with metabolic syndrome (MS). METHODS AND RESULTS: Using data from Korea Acute Myocardial Infarction Registry (KAMIR; November 2005-December 2007), a total of 1,768 MS patients with STEMI who underwent primary PCI were enrolled: The PES group was 634, SES group, 906, and ZES group, 228. The primary endpoint was major adverse cardiac event (all-cause death, re-myocardial infarction, target lesion revascularization) during 12 months follow-up. At 12 months, the cumulative incidence of primary endpoint in the PES, SES, and ZES groups was 10.9%, 9.1%, and 11.0%, respectively (P=0.086). Incidence of death, recurrent myocardial infarction, or target lesion revascularization did not differ among the 3 groups. There were 7 episodes of acute (0.3% in PES group, 0.4% in SES group, and 0.4% in ZES group, respectively, P=0.773) and 18 episodes of cumulative stent thrombosis including late stent thrombosis (0.9% in PES group, 1.0% in SES group, and 1.3% in ZES group, respectively, P=0.448). CONCLUSIONS: Implantation of SES, PES, and ZES in MS patients with STEMI undergoing primary PCI provided comparable clinical outcomes in patients enrolled in KAMIR.

Effectiveness of drug-eluting stents versus bare-metal stents in large coronary arteries in patients with acute myocardial infarction.

This study compared clinical outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in large coronary arteries in patients with acute myocardial infarction (MI). A total of 985 patients who underwent single-vessel percutaneous coronary intervention (PCI) in large coronary arteries (≥ 3.5 mm) in lesions < 25 mm were divided into DES group (n = 841) and BMS group (n = 144). Clinical outcomes during 12 months were compared. In-hospital outcome was similar between the groups. At six months, death/MI rate was not different. However, DES group had significantly lower rates of target-lesion revascularization (TLR) (1.7% vs 5.6%, P = 0.021), target-vessel revascularization (TVR) (2.2% vs 5.6%, P = 0.032), and total major adverse cardiac events (MACE) (3.4% vs 11.9%, P = 0.025). At 12 months, the rates of TLR and TVR remained lower in the DES group (2.5% vs 5.9%, P = 0.032 and 5.9% vs 3.1%, P = 0.041), but the rates of death/MI and total MACE were not statistically different. The use of DES in large vessels in the setting of acute MI is associated with lower need for repeat revascularization compared to BMS without compromising the overall safety over the course of one-year follow-up.

Temporal Trends of Bleeding Episodes during Half- vs. Standard-Dose Ticagrelor in Acute Coronary Syndrome Patients with Low Platelet Reactivity: A Randomized BLEEDING-ACS Trial.

To assess the temporal trends of bleeding episodes during half- vs. standard-dose ticagrelor in acute coronary syndrome (ACS) patients with low platelet reactivity (LPR) during standard-dose ticagrelor (90 mg bid). ACS Patients with LPR (<85 P2Y12 reaction units) (n = 122) were randomly assigned to receive either half-dose (45 mg bid) or standard-dose ticagrelor (90 mg bid). The primary endpoint was incidence of Bleeding Academic Research Consortium (BARC) bleeding at 1 week, 1, 3 and 6 months. Dyspnea and ischemic events were also evaluated. Bleeding episodes were most commonly observed at 1 month and then decreased over time. Half-dose ticagrelor did not reduce any BARC bleeding (odds ratio [OR] 0.900, 95% confidence interval [CI] 0.563-1.440, p = 0.661). However, serious bleeding (BARC type ≥2) occurred less often in half-dose ticagrelor (OR 0.284, 95% CI 0.088-0.921, p = 0.036). The rate of moderate-to-severe dyspnea was highest at 1 month, then decreased over time. Half-dose ticagrelor did not decrease moderate-to-severe dyspnea (Borg scale ≥ 3) (OR 1.066, 95% CI 0.322-3.530, p = 0.916). The risk of ischemic events was also similar between the groups. In conclusions, compared with standard-dose ticagrelor, half-dose ticagrelor reduced serious bleeding events during early period of dual-antiplatelet therapy in ACS patients with LPR; however, the risk of any bleeding events and dyspnea did not differ according to ticagrelor dose. Clinical registration: KCT0004640.

Clinical outcomes of endovascular treatment for ruptured thoracic aortic disease.

BACKGROUND/AIMS: Untreated rupture of the thoracic aorta is associated with a high mortality rate. We aimed to review the clinical results of endovascular treatment for ruptured thoracic aortic disease. METHODS: We retrospectively reviewed data on 37 patients (mean age, 67.0 ± 15.18 years) treated for ruptured thoracic aortic disease from January 2005 to May 2016. The median follow-up duration was 308 days (interquartile range, 61 to 1,036.5). The primary end-point of the study was the composite of death, secondary intervention, endoleak, and major stroke/paraplegia after endovascular treatment. RESULTS: The etiologies of ruptured thoracic aortic disease were aortic dissection (n = 11, 29.7%), intramural hematoma (n = 7, 18.9%), thoracic aortic aneurysm (n = 14, 37.8%), and traumatic aortic transection (n = 5, 13.5%). Three patients died within 24 hours of thoracic endovascular aortic repair, and one showed type I endoleak. The technical success rate was 89.2% (33/37). The in-hospital mortality rate was 13.5% (5/37); no deaths occurred during follow-up. The composite outcome rate during follow-up was 37.8% (14/37), comprising death (n = 5, 13.5%), secondary intervention (n = 5, 13.5%), endoleak (n = 5, 13.5%), and major stroke/paraplegia (n = 3, 8.1%). Left subclavian artery revascularization and proximal landing zone were not associated with the composite outcome. Low mean arterial pressure (MAP; ≤ 60 mmHg, [hazard ratio, 13.018; 95% confidence interval, 2.435 to 69.583, p = 0.003]) was the most significant predictor and high transfusion requirement in the first 24 hours was associated with event-free survival (log rank p = 0.018). CONCLUSION: Endovascular treatment achieves high technical success rates and acceptable clinical outcome. High transfusion volume and low MAP were associated with poor clinical outcomes.

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.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study.

PURPOSE: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FINDINGS: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p = 0.02) and triglycerides (-18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Whether triple antiplatelet therapy is superior or similar to dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention in the era of drug-eluting stents remains unclear. METHODS AND RESULTS: A total of 4203 ST-segment elevation myocardial infarction patients who underwent primary percutaneous coronary intervention with drug-eluting stents were analyzed retrospectively in the Korean Acute Myocardial Infarction Registry (KAMIR). They received either dual (aspirin plus clopidogrel; dual group; n=2569) or triple (aspirin plus clopidogrel plus cilostazol; triple group; n=1634) antiplatelet therapy. The triple group received additional cilostazol at least for 1 month. Various major adverse cardiac events at 8 months were compared between these 2 groups. Compared with the dual group, the triple group had a similar incidence of major bleeding events but a significantly lower incidence of in-hospital mortality. Clinical outcomes at 8 months showed that the triple group had significantly lower incidences of cardiac death (adjusted odds ratio, 0.52; 95% confidence interval, 0.32 to 0.84; P=0.007), total death (adjusted odds ratio, 0.60; 95% confidence interval, 0.41 to 0.89; P=0.010), and total major adverse cardiac events (adjusted odds ratio, 0.74; 95% confidence interval, 0.58 to 0.95; P=0.019) than the dual group. Subgroup analysis showed that older (>65 years old), female, and diabetic patients got more benefits from triple antiplatelet therapy than their counterparts who received dual antiplatelet therapy. CONCLUSIONS: Triple antiplatelet therapy seems to be superior to dual antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with drug-eluting stents. These results may provide the rationale for the use of triple antiplatelet therapy in these patients.