Background/Aims: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. Methods: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. Results: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. Conclusions In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation in vitro and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the in vitro and in vivo data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.
Animals ; Antibodies, Neutralizing* ; Cell Line ; Cell Proliferation ; Glioblastoma ; Half-Life ; Hepatocyte Growth Factor ; Heterografts ; Humans* ; In Vitro Techniques ; Macaca fascicularis ; Mice ; Mice, Nude ; Pharmacokinetics ; Phosphorylation ; Phosphotransferases ; Toxicokinetics

BACKGROUND AND OBJECTIVES: This study aims to investigate the clinical features, angiographic findings, and outcomes of younger Korean ST-segment elevation myocardial infarction (STEMI) patients. SUBJECTS AND METHODS: We analyzed major adverse cardiac events (MACE) in the Korea Acute Myocardial Infarction Registry from November 2005 to October 2010. The registered patients were divided into two groups; young age group (<65 years) and old age group (> or =65 years). RESULTS: The young age group included 5281 patients (age, 53+/-7.8 years), and the old age group included 4896 patients (age, 74.3+/-6.5 years). Male gender, smoking, family history, dyslipidemia, and metabolic syndrome were more frequently observed in the young age group than in the old age group (89.5% vs. 59.3%, p<0.001; 77.3% vs. 47.2%, p<0.001; 11% vs. 4.6%, p<0.001; 11.2% vs. 7.7%, p<0.001; 67.6% vs. 62.9%, p<0.001). Most of the young Korean adults with STEMI complained of typical chest pain (89.8%), and they had a shorter symptom-to-door time (12+/-53.2 hours vs. 17.3+/-132 hours, p=0.010). The young age group showed a favorable prognosis, which was represented by the MACE, compared with the old age group at one month (1.8% vs. 2.8%, p=0.028), six months (6.8% vs. 8.2%, p<0.001), and twelve months (10.1% vs. 11.9%, p=0.025). However, there was no significant difference in the adjusted MACE rate at one month {hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.60-1.51, p=0.828} and twelve months (HR 0.86, 95% CI 0.68-1.10, p=0.233). CONCLUSION: Younger Korean adults with STEMI have clinical outcomes similar to old aged patients, and therefore, they should be treated intensively like the elderly patients.
Adult* ; Aged ; Chest Pain ; Dyslipidemias ; Humans ; Korea ; Male ; Myocardial Infarction* ; Prognosis ; Smoke ; Smoking ; Young Adult

BACKGROUND/AIMS: To determine which drug-eluting stents are more effective in acute myocardial infarction (MI) patients with chronic kidney disease (CKD). METHODS: This study included a total of 3,566 acute MI survivors with CKD from the Korea Acute Myocardial Infarction Registry who were treated with stenting and followed up for 12 months: 1,845 patients who received sirolimus-eluting stents (SES), 1,356 who received paclitaxel-eluting stents (PES), and 365 who received zotarolimus-eluting stents (ZES). CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 calculated by the modification of diet in renal disease method. RESULTS: At the 12-month follow-up, patients receiving ZES demonstrated a higher incidence (14.8%) of major adverse cardiac events (MACEs) compared to those receiving SES (10.1%) and PES (12%, p = 0.019). The ZES patients also had a higher incidence (3.9%) of target lesion revascularization (TLR) compared to those receiving SES (1.5%) and PES (2.4%, p = 0.011). After adjusting for confounding factors, ZES was associated with a higher incidence of MACE and TLR than SES (adjusted hazard ratio [HR], 0.623; 95% confidence interval [CI], 0.442 to 0.879; p = 0.007; adjusted HR, 0.350; 95% CI, 0.165 to 0.743; p = 0.006, respectively), and with a higher rate of TLR than PES (adjusted HR, 0.471; 95% CI, 0.223 to 0.997; p = 0.049). CONCLUSIONS: Our findings suggest that ZES is less effective than SES and PES in terms of 12-month TLR, and has a higher incidence of MACE due to a higher TLR rate compared with SES, in acute MI patients with CKD.
Aged ; *Drug-Eluting Stents/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction/*etiology/mortality/*therapy ; Paclitaxel/administration & dosage ; Prospective Studies ; Registries ; Renal Insufficiency, Chronic/*complications ; Republic of Korea/epidemiology ; Sirolimus/administration & dosage/analogs & derivatives

BACKGROUND AND OBJECTIVES: Prehypertension according to JNC7 is common and is associated with increased vascular mortality. The importance of management in high-normal blood pressure (BP) is underemphasized. SUBJECTS AND METHODS: We analyzed major adverse cardiac events (MACEs) in the Korea Acute Myocardial Infarction Registry in normal BP (group I) and high-normal BP (group II) patients. RESULTS: Among 14871 patients, 159 (61+/-12.3 years, 122 males) satisfied the study indication. Six-month and one-year clinical follow-up rate was 88.9% and 85.8%, respectively. Group I had 78 patients (60.9+/-12.4 years). Group II had 81 patients (61.6+/-12.5 years). Demographics of patients were not different between groups. Treatment strategy was not different. Initial Thrombolysis in Myocardial Infarction flow grade 0 was less frequent in group II (n=32, 47.1%) than in group I (n=16, 21.9%) (p=0.001). Successful intervention rate was not different between group II (93.8%) and group I (97.1%) (p=0.590). Six-month MACE occurred in 3 patients in group I (4.4%) and 10 in group II (15.6%) (p=0.031). Compared with normal BP, the odds ratio for patients with high-normal BP was 1.147 (p=0.045, 95% confidence interval 1.011-1.402) for 6-month MACE. CONCLUSION: Even though high-normal BP patients had a better baseline clinical status, the prognosis was poorer than patients with normal BP. Therapeutic BP target goal for the patients with acute myocardial infarction should be <140/90 mm Hg, which is recommended in JNC7.
Blood Pressure ; Demography ; Emergencies ; Follow-Up Studies ; Humans ; Korea ; Myocardial Infarction ; Odds Ratio ; Prehypertension ; Prognosis

BACKGROUND: The aim of the present study was to determine the population-based prevalence of diabetes mellitus (DM) and prediabetes in a rural district of Daegu City, Korea. METHODS: Between August and November 2003, a community-based health survey of adults aged 20 years and older was performed in the rural district of Dalseong-gun in Daegu City. A total of 1,806 of all eligible individuals agreed to participate. Fasting plasma glucose was measured in all participants. Two hour oral glucose tolerance was measured in the 1,773 participants for whom there was neither an established diagnosis of DM nor evidence of DM according to fasting glucose levels. The prevalence of DM and prediabetes was determined according to the 2003 criteria of the American Diabetes Association. Subjects with prediabetes were classified into one of three categories of glucose intolerance: isolated impaired fasting glucose (IFG); isolated impaired glucose tolerance (IGT); or combined IFG and IGT. RESULTS: The prevalence of DM was 12.2%. The highest prevalence rates were observed in subjects in their seventies. A total of 34.7% of all subjects who were assigned a diagnosis of DM in the present study had not been diagnosed previously. The prevalence of prediabetes was 22.7%. The highest prevalence rates were observed in subjects in their fifties. CONCLUSION: The present study identified prevalence rates of 12.2% for DM (age-standardized prevalence rate [ASR], 6.8%), and 22.7% for prediabetes (ASR 18.5%). These results emphasize the need for community health promotion strategies to prevent or delay the onset of DM in individuals with prediabetes.
Adult ; Aged ; Diabetes Mellitus ; Fasting ; Glucose ; Glucose Tolerance Test ; Health Promotion ; Health Surveys ; Humans ; Korea ; Plasma ; Prediabetic State ; Prevalence

BACKGROUND AND OBJECTIVES: In patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, complete revascularization (CR) for non-culprit lesions is not routinely recommended. The aim of this study was to compare the clinical outcomes of multivessel compared with infarct-related artery (IRA)-only revascularization in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. SUBJECTS AND METHODS: From the Korean Acute Myocardial Infarction Registry (KAMIR) database, 1,094 STEMI patients with multivessel disease who underwent primary PCI with drug-eluting stents were enrolled in this study. The patients were divided into two groups: culprit-vessel-only revascularization (COR, n=827) group; multivessel revascularization, including non-IRA (MVR, n=267) group. The primary endpoint of this study included major adverse cardiac events (MACEs), such as death, myocardial infarction, or target or nontarget lesion revascularization at one year. RESULTS: There was no difference in clinical characteristics between the two groups. During the one-year follow-up, 102 (15.2%) patients in the COR group and 32 (14.2%) in the MVR group experienced at least one MACE (p=0.330). There were no differences between the two groups in terms of rates of death, myocardial infarction, or revascularization (2.1% vs. 2.0%, 0.7% vs. 0.8%, and 11.7% vs. 10.1%, respectively; p=0.822, 0.910, and 0.301, respectively). The MACE rate was higher in the incompletely revascularized patients than in the completely revascularized patients (15% vs. 9.5%, p=0.039), and the difference was attributable to a higher rate of nontarget vessel revascularization (8.6% vs. 1.8%, p=0.002). CONCLUSION: Although multivessel angioplasty during primary PCI for STEMI did not reduce the MACE rate compared with culprit-vessel-only PCI, CR was associated with a lower rate of repeat revascularization after multivessel PCI.
Angioplasty ; Arteries ; Coronary Artery Disease ; Drug-Eluting Stents ; Follow-Up Studies ; Glycosaminoglycans ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention

The Thrombolysis in Myocardial Infarction (TIMI) risk score (TRS) has proven value in predicting prognosis in unstable angina/non ST-elevation myocardial infarction (NSTEMI) as well as in ST-elevation myocardial infarction. The TRS system has little implication, however, in the extent of myocardial damage in high-risk patients with NSTEMI. A total of 1621 patients (63.6+/-12.2 years; 1043 males) with NSTEMI were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR). We analyzed the risk for major adverse cardiac events (MACE) during a 6-month follow-up period. The TRS system showed good correlation with MACE for patients in the low and intermediate groups but had poor correlation when the high-risk group was included (p=0.128). The MACE rate was 3.8% for TRS 1, 9.4% for TRS 2, 10.7% for TRS 3, and 12.3% for TRS 4 (HR=1.29, p=0.026). Among the biomarkers and clinical risk factors, elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) (HR=2.61, p=0.001) and Killip class above III showed good correlation with MACE (HR=0.302, p<0.001). Therefore, we revised an alternative clinical scoring system by including these two variables that reflect left ventricular dysfunction: age > 65 years, history of ischemic heart disease, Killip class above III, and elevated pro-BNP levels above the 75th percentile. This modified scoring system, when tested for validity, showed good predictive value for MACE (HR=1.64, p<0.001). Compared with the traditional TRS, the novel alternative scoring system based on age, history of ischemic heart disease, Killip class, and NT-proBNP showed a better predictive value for 6-month MACE in high-risk patients with NSTEMI.
Angina, Unstable ; Biomarkers ; Follow-Up Studies ; Humans ; Korea ; Myocardial Infarction ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; Risk Factors

PURPOSE: There is still debate about the timing of revascularization in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI). We analyzed the long-term clinical outcomes of the timing of revascularization in patients with acute NSTEMI obtained from the Korea Acute Myocardial Infarction Registry (KAMIR). MATERIALS AND METHODS: 2,845 patients with acute NSTEMI (65.6 +/- 12.5 years, 1,836 males) who were enrolled in KAMIR were included in the present study. The therapeutic strategy of NSTEMI was categorized into early invasive (within 48 hours, 65.8 +/- 12.6 years, 856 males) and late invasive treatment (65.3 +/- 12.1 years, 979 males). The initial- and long-term clinical outcomes were compared between two groups according to the level of Thrombolysis In Myocardial Infarction (TIMI) risk score. RESULTS: There were significant differences in-hospital mortality and the incidence of major adverse cardiac events during one-year clinical follow-up between two groups (2.1% vs. 4.8%, p < 0.001, 10.0% vs. 13.5%, p = 0.004, respectively). According to the TIMI risk score, there was no significant difference of long-term clinical outcomes in patients with low to moderate TIMI risk score, but significant difference in patients with high TIMI risk score (> or = 5 points). Conclusions: The old age, high Killip class, low ejection fraction, high TIMI risk score, and late invasive treatment strategy are the independent predictors for the long-term clinical outcomes in patients with NSTEMI.
Age Factors ; Aged ; Angioplasty, Transluminal, Percutaneous Coronary ; Female ; Fibrinolytic Agents/*therapeutic use ; Hemodynamics/drug effects ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction/*drug therapy/pathology/therapy ; Prospective Studies ; Thrombolytic Therapy/*methods

We sought to determine the prevalence of metabolic syndrome (MS) in patients with acute myocardial infarction and its effect on clinical outcomes. Employing data from the Korea Acute Myocardial Infarction Registry, a total of 1,990 patients suffered from acute ST-elevation myocardial infarction (STEMI) between November 2005 and December 2006 were categorized according to the National Cholesterol Education Program-Adult Treatment Panel III criteria of MS. Primary study outcomes included major adverse cardiac events (MACE) during one-year follow-up. Patients were grouped based on existence of MS: group I: MS (n=1,182, 777 men, 62.8+/-12.3 yr); group II: Non-MS (n=808, 675 men, 64.2+/-13.1 yr). Group I showed lower left ventricular ejection fraction (LVEF) (P=0.005). There were no differences between two groups in the coronary angiographic findings except for multivessel involvement (P=0.01). The incidence of in-hospital death was higher in group I than in group II (P=0.047), but the rates of composite MACE during one-year clinical follow-up showed no significant differences. Multivariate analysis showed that low LVEF, old age, MS, low high density lipoprotein cholesterol and multivessel involvement were associated with high in-hospital death rate. In conclusion, MS is an important predictor for in-hospital death in patients with STEMI.
Acute Disease ; Age Factors ; Aged ; C-Reactive Protein/analysis ; Cholesterol, LDL/blood ; Coronary Angiography ; Female ; Humans ; Male ; Metabolic Syndrome X/*complications/epidemiology ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction/*complications/mortality/therapy ; Predictive Value of Tests ; Prognosis ; Treatment Outcome ; Ventricular Dysfunction, Left/complications/physiopathology