Comparative effectiveness of moderate-intensity statin with ezetimibe therapy versus high-intensity statin monotherapy in patients with acute coronary syndrome: a nationwide cohort study.

The long-term outcome of first-line moderate-intensity statin with ezetimibe combination therapy for secondary prevention after percutaneous coronary intervention in patients with acute coronary syndrome (ACS) compared to high-intensity statin monotherapy remains elusive. The objective of this study was to compare the effectiveness of moderate-intensity statin and ezetimibe combination therapy with high-intensity statin monotherapy. We conducted a nationwide, population-based, retrospective, cohort study of patients with ACS from 2013 to 2019. The patients using combination therapy were matched (1:1) to those using monotherapy. The primary outcome was a composite of myocardial infarction, stroke and all-cause mortality. We estimated the hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards regression. After propensity score matching, 10,723 pairs were selected. Men accounted for 70% of the patients and 37% aged > 70 years. The primary endpoint occurred in 1297 patients (12.1%) in the combination group and in 1426 patients (13.3%) in the monotherapy group, and decreased risk (HR 0.85, 95% CI 0.78-0.92, P < 0.001) in the combination group. Among the patients with ACS, moderate-intensity statin with ezetimibe combination therapy was associated with decreased risk of adverse cardiovascular outcomes compared with high-intensity statin monotherapy in a nationwide population-based study representing routine clinical practice.

Trends in emergency department visits for emergency care-sensitive conditions before and during the COVID-19 pandemic: a nationwide study in Korea, 2019-2021.

OBJECTIVE: Emergency care systems worldwide have been significantly affected by the COVID-19 pandemic. This study investigated the trend of emergency department (ED) visits for emergency care-sensitive conditions (ECSCs) in Korea before and during the pandemic. METHODS: We performed a longitudinal study using the national ED database in Korea from January 2019 to December 2021. We calculated the number and incidence rate of visits for ECSCs per 100,000 ED visits, and the incidence rate ratio of 2021 relative to the value in 2019. The selected ECSCs were intracranial injury, ischemic heart disease, stroke, and cardiac arrest. RESULTS: The number of ED visits for all causes decreased by about 23% during the pandemic. The number of ED visits for intracranial injuries decreased from 166,695 in 2019 to 133,226 in 2020 and then increased to 145,165 in 2021. The number of ED visits for ischemic heart disease and stroke decreased in 2020 but increased to 2019 levels in 2021. In contrast, the number of ED visits for cardiac arrest increased from 23,903 in 2019 to 24,344 in 2020 and to 27,027 in 2021. The incidence rate and incidence rate ratio of these four ECSCs increased from 2019 to 2021, suggesting increasing relative proportions of ECSCs in total ED visits. CONCLUSION: During the COVID-19 pandemic, the number of cardiac arrests seen in the EDs increased, but that of other ECSCs decreased. The decrease in ED visits for ECSCs was not as pronounced as the decrease in ED visits for all causes during the pandemic. Further studies are needed to determine clinical outcomes in patients with ECSC during the pandemic.

Impact of Concomitant Use of Proton Pump Inhibitors and Clopidogrel on Recurrent Stroke and Myocardial Infarction.

BACKGROUND/AIMS: Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). METHODS: This study used two databases for two different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS data base converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study based on large-scale propensity score matching. RESULTS: In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1216 patients with history of MI within1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 (95% confidence interval (CI); 1.83-2.38); the RR showed an increasing trend parallel to the time from the beginning of PPI co-prescription. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group (Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, p = 0.04). The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, p = 0.23). The impact of individual PPIs on stroke and MI showed different patterns. CONCLUSIONS: A PPI co-prescription >4 weeks with clopidogrel was associated with hospitalization of recurrent stroke within 1 year of initial diagnosis; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.

Trends in emergency department visits for suicide attempts before and during the COVID-19 pandemic in Korea: A nationwide study, 2016-2021.

BACKGROUND: There is increasing concern that the effects of the COVID-19 pandemic will result in excess suicides by increasing known risk factors, such as suicide attempts. However, evidence on the long-term impacts of COVID-19 on suicide attempts is lacking. We aimed to assess the short- and long-term effects of the COVID-19 pandemic on patients with suicide attempts in emergency departments (EDs) and to evaluate age- and sex-specific differences. METHOD: We conducted nationwide cross-sectional study among patients with suicide attempts in the ED from 2016 to 2021. The trend test were used to determine whether study subjects were affected by changes in ED visits for suicide attempts. We estimated the average annual percentage change (APC) stratified by sex and age groups. RESULTS: The number of ED visits related to suicide attempts increased from 27,581 in 2016 to 37,719 in 2021. In particular, it decreased immediately after the COVID-19 pandemic but increased again in 2021. We identified that the average APC increased by 6.8 % overall, 1.6 % among males, and 10.8 % among females. Moreover, the APC of trend sharply increased in patients aged 10s and 20s. The in-hospital mortality was 3.6 % for females, compared to 9.5 % for males, which showed sex differences. LIMITATIONS: This study was limited to confirming causal relationship based on a descriptive study. CONCLUSIONS: The incidence of suicide attempts in ED has increased in Korea. In particular, there was a sharp increase among women, adolescents and young adults. Patient-tailored treatment and preventive medical system for suicide attempts is important.

Potentially avoidable hospitalizations for older patients transferred from long-term care hospitals: a nationwide cross-sectional analysis of potential healthcare consequences.

Multiple chronic disorders and disabilities among older patients in long term care hospitals (LTCH) tends to increase the healthcare burden by causing overcrowding, particularly in emergency departments. Therefore, access to timely and adequate healthcare for LTCH patients is an increasingly important issue, and potentially avoidable hospitalizations (PAHs) and hospitalizations during non-office hours can result as indicators of emergency department overcrowding. The study aimed to evaluate PAHs and hospitalizations during non-office hours in emergency departments for older patients transferred from LTCH compared to patients living at home. We performed a cross-sectional study using the National Emergency Department Information System database from January 2018 to December 2019, in South Korea, with older patients (≥ 65 years) who visited nationwide emergency departments. Adjusted odds ratio (aOR) and 95% confidence interval (CI) for indicators of overcrowding as PAHs and hospitalizations during non-office hours were calculated by logistic regression. Among the 2,177,663 older patients who visited the emergency departments, 98,434 patients were living in LTCH and 2,079,229 patients were living at home. The older patients living in LTCH was associated with PAHs (aOR: 1.90, 95% CI 1.87-1.94) and hospitalizations during non-office hours (aOR: 1.76, 95% CI 1.73-1.78). LTCH patients showed more hospital visits, extended stay in the emergency department, greater prevalence of chronic diseases, greater rates of transfer as well as higher admission rates and mortality as compared to the patients living at home. The LTCH older patients were associated with the indicators of emergency department overcrowding, which impacts health care quality in hospitals. Introduction of policy and training programs for LTCH staff are recommended to manage vulnerable groups in advance.

The impact of COVID-19 on the patterns of emergency department visits among pediatric patients.

OBJECTIVES: This study aimed to investigate the patterns of pediatric patients visiting emergency departments (EDs) before and after the COVID-19 pandemic and evaluate the interactive effect between the COVID-19 outbreak and age groups. METHODS: We performed a cross-sectional study using the nationwide emergency patient database in Korea from January 2019 to December 2020. Pediatric patients (≤18 years) who visited all 402 nationwide EDs were included. The age- and sex-standardized incidence rates of pediatric ED visits per 1,000,000 person-days were calculated, and the incidence rate ratio (IRR) was calculated. The adjusted odds ratio (aOR) and 95% confidence interval (CI) of in-hospital mortality were calculated by a multivariable logistic regression. RESULTS: Among 2,808,756 patients, 1,835,045 (65.3%) patients visited before COVID-19, and 973,711 (34.7%) patients visited after the COVID-19 period. The standardized incidence rates of ED visits per 1,000,000 person-days were 589.3 in the before COVID-19 group and 326.9 in the after COVID-19 group (IRR (95% CI): 0.55 (0.53-0.58)). By diagnosis, the IRRs (95% CI) of mental health disorders (0.84 (0.42-1.65)) and self-harm or suicidal attempts (0.99 (0.38-2.59) were not significant, while the incidence rate of infectious disease was significantly decreased (0.48 (0.42-0.54)). The aOR (95% CI) of in-hospital mortality after COVID-19 was 1.58 (1.44-1.73) compared to that before COVID-19. CONCLUSIONS: During the COVID-19 pandemic, the incidence of pediatric ED visits decreased, and these effects differed by age group. Age-specific policies are needed to ensure that children receive the care they need at the right time.

Comparison of risk of cardiovascular disease related adverse events between selective serotonin reuptake inhibitor users and serotonin norepinephrine reuptake inhibitor users in Korean adult patients with depression: retrospective cohort study.

Serotonin norepinephrine reuptake inhibitor (SNRI) has been increasingly administered, but the associated cardiovascular disease (CVD) related adverse events risk is not clearly understood. So, we conducted a cohort study to identified CVD-related adverse events risk of SNRI comparing to selective serotonin reuptake inhibitor (SSRI). We used Korea Health Insurance Review and Assessment data. During the period from April 2009 to March 2011, patients who were prescribed SSRI or SNRI for depression, who were followed up till March 2018, were the subjects. Hemorrhagic stroke, ischemic stroke, and myocardial infarction were selected as the outcomes. High-dimensional propensity scores were used to adjust the unmeasured confounders. the cox proportional hazard model was used for the statistical analysis. A total of 1,016,136 patients diagnosed with depression over the age of 20 were screened and there were 64,739 SSRI users and 3,711 SNRI users in the group of patients. The adjusted hazard ratio did not differ between the two groups, but the subgroup analysis according to comorbidities showed a high risk of hemorrhagic stroke in SNRI users with hypertension or diabetes mellitus.

Signals of Adverse Drug Reactions of Paliperidone Compared to Other Atypical Antipsychotics Using the Korean Adverse Event Reporting System Database.

BACKGROUND AND OBJECTIVES: Schizophrenia is a severe public health problem and one of the top ten causes of disability, affecting about 1.1% of the world's population. Paliperidone is a new atypical antipsychotic used to treat schizophrenia. Several case reports about unexpected adverse drug reactions of paliperidone have been consistently reported around the world. The purpose of this study was to detect signals of adverse events (AEs) after paliperidone treatment using the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System database (KIDS-KD). METHODS: We applied data-mining techniques based on a disproportionality analysis to KIDS-KD consisting of spontaneously reported AE reports related to atypical antipsychotics between January 2009 and December 2018. We calculated three data-mining indices of paliperidone compared to all other atypical antipsychotics. We defined signals that satisfied all three criteria of the indices. We checked if the signals identified were included in the drug labels for South Korea, the USA, the UK, Japan, Germany, and France. RESULTS: The total number of suspected AE reports related to all atypical antipsychotics in the KIDS-KD from January 2009 to December 2018 was 43,970. Among those, the number of AE reports related to paliperidone was 9453. Overall, 13 signals such as seborrhea, hallucination, obesity, gingivitis, and intervertebral disorder were classified into newly detected meaningful signals. CONCLUSION: We detected new AE signals of paliperidone that were not listed on the drug labels of six countries, and many that were related to psychotic symptoms, metabolic problems, and endocrine disorders.

Conducting and Reporting a Clinical Research Using Korean Healthcare Claims Database.

An increasing number of studies are using healthcare claims databases to assess healthcare intervention utilization patterns or outcomes in real-world clinical settings. However, methodological issues affecting study design or data analysis can make conducting and reporting these types of studies difficult. This review presents an overview of the types of information contained in claims data, describes some advantages and limitations of using claims data for research purposes, and outlines steps for utilizing the Korea Health Insurance Review and Assessment and National Health Insurance Service databases. The study also reviews epidemiological approaches utilizing healthcare claims databases (including cross-sectional, case-control, case-crossover, and cohort designs) with respect to protocol development, analysis, and reporting of results, and introduces relevant guidelines and checklists, including the Guidelines for Good Pharmacoepidemiology Practices, the Strengthening the Reporting of Observational Studies in Epidemiology checklist, and the Risk of Bias in Nonrandomized Studies of Interventions tool.

Duloxetine and cardiovascular adverse events: A systematic review and meta-analysis.

Duloxetine has been increasingly administered, but the associated cardiovascular adverse event risk is not clearly understood. Therefore, we identified the association between duloxetine and cardiovascular adverse events through an analysis of heart rate and blood pressure change. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and psycINFO in June 2019. The title, abstract, and full text were checked in order to obtain articles. A meta-analysis was conducted with random effect model and quality of articles was evaluated using Cochrane Risk of Bias 2.0. The manuscript has been written according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) harm checklist. A total of 4009 studies were screened by the title and abstract. After reviewing 186 full texts, 17 studies were finally selected for the meta-analysis. Nine of the 17 studied duloxetine given for mood disorders and 8 for pain control. The duration of 14 studies was under 13 weeks. Cardiovascular adverse events (hypertension, myocardial infarction, transient ischemic attack, tachycardia atrial fibrillation, and cerebrovascular accident) were reported. The meta-analysis demonstrated that duloxetine increased heart rate by 2.22 beats/min (95% confidence intervals [CIs]: 1.53, 2.91) and diastolic blood pressure by 0.82 mmHg (95% CI: 0.17, 1.47). Our findings may be the signal for the safety of cardiovascular disease for short-term use of duloxetine. Well-designed pharmaco-epidemiological studies evaluating the causal relationship between long-term use of duloxetine and cardiovascular disease is still necessary.

Comparison of bleeding risks among non-vitamin K antagonist oral anticoagulants using the Korea adverse event reporting system database.

BACKGROUND: In order to ensure safer use of non-vitamin K antagonist oral anticoagulants (NOACs), continuously detecting unexpected adverse drug reactions (ADRs) after market approval is necessary. METHODS: We performed disproportionality analysis to evaluate association between ADRs and NOACs including apixaban, dabigatran, and rivaroxaban using data from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System database (KIDS-KD) between 2012 and 2016. There was no significant signal other than bleeding when considering quantity, signal strength, seriousness, and causality. In order to evaluate the NOAC reports about bleeding, we selected 62 WHO-ART diagnostic codes associated with bleeding. Among the 26 codes that referred to major bleeding, 18 codes referred to gastrointestinal bleeding and 8 were referred to intracranial bleeding. We evaluated the significance of the signals using reporting odds ratios (RORs) adjusted for age and sex. RESULTS: Treatments with apixaban, dabigatran, and rivaroxaban were associated with 1989, 1668, and 2960 adverse events, respectively. Any type of bleeding with apixaban, dabigatran, rivaroxaban, and warfarin was reported in 174 (8.8%), 209 (12.5%), 523 (17.8%), and 620 (9.5%) events, respectively. For any bleeding, adjusted RORs of apixaban, dabigatran, and rivaroxaban were 0.99 [95% confidence interval (CI): 0.83-1.17], 1.47 (95% CI: 1.25-1.75), and 2.48 (95% CI: 2.16-2.84), respectively. With respect to major bleeding, the adjusted RORs of apixaban, dabigatran, and rivaroxaban were 1.08 (95% CI: 0.82-1.41), 1.46 (95% CI: 1.10-1.90), and 1.82 (95% CI: 1.43-2.32), respectively. CONCLUSION: Rivaroxaban might have stronger association with bleeding than apixaban and dabigatran.

Fluoxetine and Risk of Bleeding in Patients Aged 60 Years and Older Using the Korea Adverse Event Reporting System Database: A Case/Noncase Study.

BACKGROUND: Depression, the leading cause of nonfatal disease burden, has a strong correlation with suicide and affects approximately 7% of the general elderly population. Adverse drug reactions in older patients are particularly important because of reduced drug metabolism, polypharmacy, drug-drug interactions, and drug-disease interactions. Fluoxetine is the first representative selective serotonin reuptake inhibitor but is associated with the possibility of hemorrhage based on its mechanism of action. Serious cases of gastrointestinal bleeding and cerebral hemorrhage have been reported, raising concerns about the safety of this drug. METHODS: We detected signals of bleeding risk associated with fluoxetine in an elderly population using the Korea Adverse Event Reporting System database. Reporting odds ratios and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 16,517 adverse events related to antidepressants were reported. The reporting odds ratios for fluoxetine were 2.34 (95% CI, 1.03-5.34) for total bleeding, 4.41 (95% CI, 1.60-12.15) for major bleeding, 2.06 (95% CI, 0.28-15.03) for gastrointestinal bleeding, and 6.12 (95% CI, 2.14-22.60) for brain hemorrhage compared with those of all other antidepressants. CONCLUSIONS: We detected safety signals with total bleeding, major bleeding, and brain hemorrhage related to fluoxetine. For patients with a high risk of bleeding, such as the elderly population, prescribing antidepressants other than fluoxetine can be considered. The results of this study provide preliminary evidence of a relationship between fluoxetine and hemorrhage but have wide 95% CIs. Further pharmacoepidemiological studies will be needed to confirm the risk of bleeding associated with fluoxetine.

Impact of the Health Insurance Coverage Policy on Oral Anticoagulant Prescription among Patients with Atrial Fibrillation in Korea from 2014 to 2016.

BACKGROUND: To evaluate oral anticoagulant (OAC) utilization in patients with atrial fibrillation after the changes in the health insurance coverage policy in July 2015. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Samples (HIRA-NPS) between 2014 and 2016. The HIRA-NPS, including approximately 1.4 million individuals, is a stratified random sample of 3% of the entire Korean population using 16 age groups and 2 sex groups. The HIRA-NPS comprises personal and medical information such as surgical or medical treatment provided, diagnoses, age, sex, region of medical institution, and clinician characteristics. The studied drugs included non-vitamin K antagonist OACs (NOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban, and were compared with warfarin. We analyzed drug utilization pattern under three aspects: person, time, and place. RESULTS: The number of patients with atrial fibrillation who were prescribed OACs was 3,114, 3,954, and 4,828; and the proportions of prescribed NOACs to total OACs were 5.1%, 36.2%, and 60.8% in 2014, 2015, and 2016, respectively. The growth rate of OACs prescription increased from 61.4 patients/quarter before June 2015 to 147.7 patients/quarter thereafter. These changes were predominantly in elderly individuals aged more than 70 years. The proportion of NOACs to OACs showed significant regional difference. CONCLUSION: The change of health insurance coverage policy substantially influenced OACs prescription pattern in whole Korean region. But the impact has been significantly different among regions and age groups, which provides the evidence for developing standard clinical practice guideline on OACs use.

Data-mining for detecting signals of adverse drug reactions of fluoxetine using the Korea Adverse Event Reporting System (KAERS) database.

Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database. We defined signals in this study by the reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) indices. The KAERS database included 860,224 AE reports, among which 866 reports contained fluoxetine. We compared the labels of fluoxetine among the United States, UK, Germany, France, China, and Korea. Some of the signals, including emotional lability, myositis, spinal stenosis, paradoxical drug reaction, drug dependence, extrapyramidal disorder, adrenal insufficiency, and intracranial hemorrhage, were not labeled in the six countries. In conclusion, we identified new signals that were not known at the time of market approval. However, certain factors should be required for signal evaluation, such as clinical significance, preventability, and causality of the detected signals.