1.Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
Jung-Joon CHA ; Soon Jun HONG ; Subin LIM ; Ju Hyeon KIM ; Hyung Joon JOO ; Jae Hyoung PARK ; Cheol Woong YU ; Do-Sun LIM ; Jang Young KIM ; Jin-Ok JEONG ; Jeong-Hun SHIN ; Chi Young SHIM ; Jong-Young LEE ; Young-Hyo LIM ; Sung Ha PARK ; Eun Joo CHO ; Hasung KIM ; Jungkuk LEE ; Ki-Chul SUNG ;
Korean Circulation Journal 2024;54(9):534-544
Background and Objectives:
Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middleaged patients when compared with statin monotherapy.
Methods:
Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.
Results:
The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs.10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980–1.064; p=0.309).Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460–0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.
Conclusions
Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
2.Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
Jung-Joon CHA ; Soon Jun HONG ; Subin LIM ; Ju Hyeon KIM ; Hyung Joon JOO ; Jae Hyoung PARK ; Cheol Woong YU ; Do-Sun LIM ; Jang Young KIM ; Jin-Ok JEONG ; Jeong-Hun SHIN ; Chi Young SHIM ; Jong-Young LEE ; Young-Hyo LIM ; Sung Ha PARK ; Eun Joo CHO ; Hasung KIM ; Jungkuk LEE ; Ki-Chul SUNG ;
Korean Circulation Journal 2024;54(9):534-544
Background and Objectives:
Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middleaged patients when compared with statin monotherapy.
Methods:
Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.
Results:
The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs.10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980–1.064; p=0.309).Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460–0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.
Conclusions
Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
3.Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
Jung-Joon CHA ; Soon Jun HONG ; Subin LIM ; Ju Hyeon KIM ; Hyung Joon JOO ; Jae Hyoung PARK ; Cheol Woong YU ; Do-Sun LIM ; Jang Young KIM ; Jin-Ok JEONG ; Jeong-Hun SHIN ; Chi Young SHIM ; Jong-Young LEE ; Young-Hyo LIM ; Sung Ha PARK ; Eun Joo CHO ; Hasung KIM ; Jungkuk LEE ; Ki-Chul SUNG ;
Korean Circulation Journal 2024;54(9):534-544
Background and Objectives:
Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middleaged patients when compared with statin monotherapy.
Methods:
Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.
Results:
The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs.10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980–1.064; p=0.309).Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460–0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.
Conclusions
Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
4.Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
Jung-Joon CHA ; Soon Jun HONG ; Subin LIM ; Ju Hyeon KIM ; Hyung Joon JOO ; Jae Hyoung PARK ; Cheol Woong YU ; Do-Sun LIM ; Jang Young KIM ; Jin-Ok JEONG ; Jeong-Hun SHIN ; Chi Young SHIM ; Jong-Young LEE ; Young-Hyo LIM ; Sung Ha PARK ; Eun Joo CHO ; Hasung KIM ; Jungkuk LEE ; Ki-Chul SUNG ;
Korean Circulation Journal 2024;54(9):534-544
Background and Objectives:
Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middleaged patients when compared with statin monotherapy.
Methods:
Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years.
Results:
The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs.10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980–1.064; p=0.309).Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460–0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups.
Conclusions
Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.
5.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
6.Effect of the human papillomavirus vaccine on the risk of genital warts: a nationwide cohort study of Korean adolescent girls
Jaeyoung CHO ; Eun Mi KIM ; Jihye KIM ; Ju-Young SHIN ; Eui Hyeok KIM ; Jong Heon PARK ; Seunghyun Lewis KWON ; Geun-Yong KWON ; Soon-Ae SHIN ; Jaiyong KIM
Epidemiology and Health 2024;46(1):e2024040-
OBJECTIVES:
The purpose of this study was to assess the effectiveness of human papillomavirus (HPV) vaccination administered to adolescent girls through Korea’s National Immunization Program.
METHODS:
This retrospective cohort study included patients who were 12-13 years old, whether vaccinated or unvaccinated, between July 2016 and December 2017. The incidence of genital warts (GWs) was monitored through 2021. Time-stratified hazard ratios (HRs) were estimated, adjusting for birth year, socioeconomic status, and the level of urbanization of the region, and were presented with 95% confidence intervals (CIs). Data were sourced from the Immunization Registry Integration System, linked with the National Health Information Database.
RESULTS:
The study included 332,062 adolescent girls, with an average follow-up period of approximately 4.6 years. Except for the first year, the HRs for the vaccinated group were lower than those for the unvaccinated group. The HRs for specific cut-off years were as follows: year 2, 0.62 (95% CI, 0.31 to 1.13); year 3, 0.58 (95% CI, 0.35 to 0.96); and year 4 and beyond, 0.39 (95% CI, 0.28 to 0.52).
CONCLUSIONS
Our findings indicate that HPV vaccination was associated with a reduction in the risk of GWs among adolescent girls. Notably, this reduction became significant as the incidence of GWs increased with age.
7.Clinical Practice Guideline for Percutaneous Endoscopic Gastrostomy
Chung Hyun TAE ; Ju Yup LEE ; Moon Kyung JOO ; Chan Hyuk PARK ; Eun Jeong GONG ; Cheol Min SHIN ; Hyun LIM ; Hyuk Soon CHOI ; Miyoung CHOI ; Sang Hoon KIM ; Chul-Hyun LIM ; Jeong-Sik BYEON ; Ki-Nam SHIM ; Geun Am SONG ; Moon Sung LEE ; Jong-Jae PARK ; Oh Young LEE ;
Gut and Liver 2024;18(1):10-26
With an aging population, the number of patients with difficulty swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. Long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach, aided endoscopically, which may be an alternative to a nasogastric tube when enteral nutritional is required for 4 weeks or more. This paper is the first Korean clinical guideline for PEG. It was developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tubes removal for PEG based on the currently available clinical evidence.
8.The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study
Byung-Wook KIM ; Jong Jae PARK ; Hee Seok MOON ; Wan Sik LEE ; Ki-Nam SHIM ; Gwang Ho BAIK ; Yun Jeong LIM ; Hang Lak LEE ; Young Hoon YOUN ; Jun Chul PARK ; In-Kyung SUNG ; Hyunsoo CHUNG ; Jeong Seop MOON ; Gwang Ha KIM ; Su Jin HONG ; Hyuk Soon CHOI
Gut and Liver 2024;18(2):257-264
Background/Aims:
Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases.This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers.
Methods:
Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed.
Results:
One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups.
Conclusions
Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.
9.Energy Metabolism in Human Pluripotent Stem and Differentiated Cells Compared Using a Seahorse XF96 Extracellular Flux Analyzer
Hyun Kyu KIM ; Yena SONG ; Minji KYE ; Byeongho YU ; Sang Beom PARK ; Ji Hyeon KIM ; Sung-Hwan MOON ; Hyungkyu CHOI ; Jong-Seok MOON ; Jae Sang OH ; Man Ryul LEE
International Journal of Stem Cells 2024;17(2):194-203
Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2∼4 and 2∼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.
10.Therapeutic Outcomes and Electrophysiological Biomarkers in Anti-Myelin-Associated Glycoprotein Neuropathy:A Multicenter Cohort Study in South Korea
Young Gi MIN ; Hee-Jo HAN ; Ha Young SHIN ; Jong-Gyu BAEK ; Jun-Soon KIM ; Kyung-Seok PARK ; Seol-Hee BAEK ; Ilhan YOO ; So-Young HUH ; Young Nam KWON ; Seok-Jin CHOI ; Sung-Min KIM ; Yoon-Ho HONG ; Jung-Joon SUNG
Journal of Clinical Neurology 2024;20(1):50-58
Background:
and Purpose Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management.
Methods:
This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases.
Results:
The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792).
Conclusions
Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

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