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Although both angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs) are all suitable for the initiation of antihypertensive treatment, studies investigating efficacy and safety between ARBs and CCBs are limited, and there is no previous study comparing their clinical outcomes during long-term follow-up periods in real world setting. We compared cardiovascular (CV) events between ARBs and CCBs in 464,948 hypertensive adults using the Korean National Health Insurance Service database during a 3-year follow-up. The patients with hypertension without heart failure, ischemic heart disease, cerebrovascular disease, or peripheral artery disease were enrolled. The CV events between only single prescription of CCBs and ARBs were finally compared. The primary endpoint for this study was the first occurrence of a major adverse CV events, defined as the composite of all-cause death, cardiac death, nonfatal myocardial infarction, or nonfatal stroke. ARB was significantly more administered in male and patients with higher income, diabetes mellitus, chronic kidney diseases, and higher Charlson comorbidity index. The primary endpoints occurred in 10,526 patients (5.2%) in the ARB group and in 19,363 patients (7.3%) in the CCB group (p < 0.001) during a 3-year follow-up (HR 0.96, 95% CI 0.93–0.98). All the components of CV events including all-cause death, cardiac death, nonfatal myocardial infarction, and nonfatal stroke occurred more frequently in the CCB group. With multivariable models adjusting age, sex, income, diabetes, chronic kidney disease, and Charlson comorbidity index, the primary endpoints less frequently developed in the ARB group than in the CCB group (HR 0.957, 95% CI 0.933–0.983, p < 0.001). After the propensity-score matching, baseline characteristics were similar and still showed significantly better primary endpoints in ARB group than CCB group (5.3% vs. 5.8%, p < 0.001). In this nationwide population-based simple hypertension study, administration of ARBs showed superior protection against CV events than CCBs during a 3-year follow-up. Our results suggest that ARBs could be preferred over CCBs as the initial choice of antihypertensive treatment regardless of age in real-world practice.

The association of left ventricular ejection fraction (LVEF) with procedural and long-term outcomes after state-of-the-art percutaneous coronary intervention (PCI) of bifurcation lesions remains unsettled. A total of 5,333 patients who underwent contemporary coronary bifurcation PCI were included in the intercontinental retrospective combined insights from the unified RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) and COBIS (COronary BIfurcation Stenting) III bifurcation registries. Of 5,003 patients (93.8%) with known baseline LVEF, 244 (4.9%) had LVEF <40% (bifurcation with reduced ejection fraction [BIFrEF] group), 430 (8.6%) had LVEF 40% to 49% (bifurcation with mildly reduced ejection fraction [BIFmEF] group) and 4,329 (86.5%) had ejection fraction (EF) ≥50% (bifurcation with preserved ejection fraction [BIFpEF] group). The primary end point was the Kaplan-Meier estimate of major adverse cardiac events (MACEs) (a composite of all-cause death, myocardial infarction, and target vessel revascularization). Patients with BIFrEF had a more complex clinical profile and coronary anatomy. No difference in procedural (30 days) MACE was observed across EF categories, also after adjustment for in-study outcome predictors (BIFrEF vs BIFmEF: adjusted hazard ratio [adj-HR] 1.39, 95% confidence interval [CI] 0.37 to 5.21, p = 0.626; BIFrEF vs BIFpEF: adj-HR 1.11, 95% CI 0.25 to 2.87, p = 0.883; BIFmEF vs BIFpEF: adj-HR 0.81, 95% CI 0.29 to 2.27, p = 0.683). BIFrEF was independently associated with long-term MACE (median follow-up 21 months, interquartile range 10 to 21 months) than both BIFmEF (adj-HR 2.20, 95% CI 1.41 to 3.41, p <0.001) and BIFpEF (adj-HR 1.91, 95% CI 1.41 to 2.60, p <0.001) groups, although no difference was observed between BIFmEF and BIFpEF groups (adj-HR 0.87, 95% CI 0.61 to 1.24, p = 0.449). In conclusion, in patients who underwent PCI of a coronary bifurcation lesion according to contemporary clinical practice, reduced LVEF (<40%), although a strong predictor of long-term MACEs, does not affect procedural outcomes.

Identification of obstructive coronary artery disease (OCAD) in patients with chest pain is a clinical challenge. The value of corrected QT interval (QTc) for the prediction of OCAD has yet to be established. We consecutively enrolled 1741 patients with suspected angina. The presence of obstructive OCAD was defined as ≥ 50% diameter stenosis by coronary angiography. The pre-test probability was evaluated by combining QTc prolongation with the CAD Consortium clinical score (CAD2) and the updated Diamond-Forrester (UDF) score. OCAD was detected in 661 patients (38.0%). QTc was longer in patients with OCAD compared with those without OCAD (444 ± 34 vs. 429 ± 28 ms, p < 0.001). QTc was increased by the severity of OCAD (P < 0.001). QTc prolongation was associated with OCAD (odds ratio (OR), 2.27; 95% confidence interval (CI), 1.81–2.85). With QTc, the C-statistics increased significantly from 0.68 (95% CI 0.66–0.71) to 0.76 (95% CI 0.74–0.78) in the CAD2 and from 0.64 (95% CI 0.62–0.67) to 0.74 (95% CI 0.72–0.77) in the UDF score, respectively. QT prolongation predicted the presence of OCAD and the QTc improved model performance to predict OCAD compared with CAD2 or UDF scores in patients with suspected angina.

Combination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia. I-ROSETTE (Ildong ROSuvastatin & ezETimibe for hypercholesTElolemia) was an 8-week, double-blind, multicenter, Phase III randomized controlled trial conducted at 20 hospitals in the Republic of Korea. Patients with hypercholesterolemia who required medical treatment according to National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for participation in the study. Patients were randomly assigned to receive ezetimibe 10 mg/rosuvastatin 20 mg, ezetimibe 10 mg/rosuvastatin 10 mg, ezetimibe 10 mg/rosuvastatin 5 mg, rosuvastatin 20 mg, rosuvastatin 10 mg, or rosuvastatin 5 mg in a 1:1:1:1:1:1 ratio. The primary end point was the difference in the mean percent change from baseline in LDL-C level after 8 weeks of treatment between the ezetimibe/rosuvastatin and rosuvastatin treatment groups. All patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. Of 396 patients, 389 with efficacy data were analyzed. Baseline characteristics among 6 groups were similar. After 8 weeks of double-blind treatment, the percent changes in adjusted mean LDL-C levels at week 8 compared with baseline values were –57.0% (2.1%) and –44.4% (2.1%) in the total ezetimibe/rosuvastatin and total rosuvastatin groups, respectively (P < 0.001). The LDL-C–lowering efficacy of each of the ezetimibe/rosuvastatin combinations was superior to that of each of the respective doses of rosuvastatin. The mean percent change in LDL-C level in all ezetimibe/rosuvastatin combination groups was >50%. The number of patients who achieved target LDL-C levels at week 8 was significantly greater in the ezetimibe/rosuvastatin group (180 [92.3%] of 195 patients) than in the rosuvastatin monotherapy group (155 [79.9%] of 194 patients) (P < 0.001). There were no significant differences in the incidence of overall AEs, adverse drug reactions, and serious AEs; laboratory findings, including liver function test results and creatinine kinase levels, were comparable between groups. Fixed-dose combinations of ezetimibe/rosuvastatin significantly improved lipid profiles in patients with hypercholesterolemia compared with rosuvastatin monotherapy. All groups treated with rosuvastatin and ezetimibe reported a decrease in mean LDL-C level >50%. The safety and tolerability of ezetimibe/rosuvastatin therapy were comparable with those of rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT02749994.

Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed. In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete. Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference −0·78%; 90% CI −2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001). Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction. Hanmi Pharmaceutical.

Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34- mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34- mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.

Percutaneous coronary interventions performed at coronary bifurcations yield high rates of stent thrombosis (ST). The aim of the present study was to investigate the predictors of ST in contemporary coronary bifurcation percutaneous coronary interventions. We retrospectively investigated the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry on coronary bifurcations to assess the incidence and predictors of definite ST, which were the study primary endpoints. Predictors of ST among patients on dual antiplatelet therapy (DAPT) were also examined. A total of 5330 patients were included. After a mean 2-years follow-up, 64 (1.2%) patients experienced ST. 42 (65.6%) ST patients were on DAPT. At multivariable analysis, age (HR 1.02, CI 1.01 to 1.05, p = 0,027), smoking status (HR 2.57, CI 1.49 to 4.44, p = 0.001), chronic kidney disease (HR 2.26, CI 1.24 to 4.12, p = 0.007) and a 2-stent strategy (HR 2.38, CI 1.37 to 4.14, p = 0.002) were independent predictors of ST, whereas intracoronary imaging (HR 0.42, CI 0.23 to 0.78, p = 0.006) and final kissing balloon (FKB) (HR 0.48, CI 0.29 to 0.82, p = 0.007) were protective against ST. Among patients on DAPT, smoking status and a 2-stent strategy significantly increased the risk of ST, while intracoronary imaging and FKB reduced the risk. In conclusion, age, smoking status, chronic kidney disease and a 2-stent strategy were significant predictors of ST, whereas intracoronary imaging use and FKB had a protective effect. Only smoking status and a 2-stent strategy significantly predicted ST in DAPT subgroup, while intracoronary imaging and FKB had a protective role.

Optimal dual antiplatelet therapy (DAPT) duration for patients undergoing percutaneous coronary intervention (PCI) for coronary bifurcations is an unmet issue. The BIFURCAT registry was obtained by merging two registries on coronary bifurcations. Three groups were compared in a two-by-two fashion: short-term DAPT (≤ 6 months), intermediate-term DAPT (6-12 months) and extended DAPT (>12 months). Major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction (MI), target-lesion revascularization and stent thrombosis) were the primary endpoint. Single components of MACE were the secondary endpoints. Events were appraised according to the clinical presentation: chronic coronary syndrome (CCS) versus acute coronary syndrome (ACS). 5537 patients (3231 ACS, 2306 CCS) were included. After a median follow-up of 2.1 years (IQR 0.9-2.2), extended DAPT was associated with a lower incidence of MACE compared with intermediate-term DAPT (2.8% versus 3.4%, adjusted HR 0.23 [0.1-0.54], p <0.001), driven by a reduction of all-cause death in the ACS cohort. In the CCS cohort, an extended DAPT strategy was not associated with a reduced risk of MACE. In conclusion, among real-world patients receiving PCI for coronary bifurcation, an extended DAPT strategy was associated with a reduction of MACE in ACS but not in CCS patients.

We performed layer-specific strain analysis with speckle-tracking echocardiography to investigate the transmural difference of myocardial damage as the predicting factor for the viability of damaged myocardium in patients with ST segment elevation myocardial infarction (STEMI). We analysed patients with acute STEMI who had undergone primary percutaneous coronary intervention and echocardiography within 24 h from the intervention and 2 months after the event. Segmental strains of the left ventricular (LV) endocardium, myocardium, epicardium, and strain gradient (SG) between the endocardium and epicardium were evaluated. In 34 patients, 112 akinetic/dyskinetic and 94 hypokinetic segments were observed among 612 segments of the LV at baseline, and 65 akinetic/dyskinetic segments had viability. In our study, layer-specific strains were gradually deteriorated by their wall motion. SG was augmented in the hypokinetic segments where inhomogeneous wall motion impairment was progressed. SG in the akinetic/dyskinetic segments was different between the viable and non-viable myocardium and was maintained in viable segments. We therefore believe that significantly reduced SG is indicative of irreversible transmural damage in the acute stage of STEMI and can be suitably used as a parameter for predicting myocardial viability.

Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154–6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.