Comparison of heart failure risk and medical costs between patients with type 2 diabetes mellitus treated with dapagliflozin and dipeptidyl peptidase-4 inhibitors: a nationwide population-based cohort study.

BACKGROUND: Dapagliflozin is one of the novel glucose-lowering agents, which has recently been reported to reduce the risk of hospitalization for heart failure (hHF). The present study aimed to compare the differences between the risk of hHF after using dapagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as second-line drugs for the treatment of type 2 diabetes mellitus using the latest nationwide population data in Korea. Additionally, we aimed to examine the impact of clinical outcomes on direct medical costs in the two groups. METHODS: The present population-based, retrospective cohort study was conducted using the nationwide claims data between September 01, 2014 and June 30, 2018. New users of dapagliflozin and DPP-4i were identified from the database and the differences in patients' characteristics between the two groups were analyzed using propensity score-weighted analysis. Cox proportional hazards regression analysis was used to estimate the risk of hHF. A simple model was used for the estimation of direct medical costs for 3 years. RESULTS: In total, 23,147 patients in the dapagliflozin group and 237,187 patients in the DPP-4i group were selected for the analysis. The incidence rates of hHF were 3.86 and 6.79 per 1000 person-years in the dapagliflozin and DPP-4i groups, respectively. In the entire study population, the hazard ratio for hHF in the dapagliflozin group compared to the DPP-4i group was 0.58 (95% confidence interval 0.46-0.74), with 0.55 (95% confidence interval 0.41-0.74) among patients with underlying cardiovascular disease and 0.66 (95% confidence interval 0.46-0.95) among patients without underlying cardiovascular disease. The direct medical costs were $57,787 lower in the dapagliflozin group than in the DPP-4i group for 3 years. CONCLUSIONS: This study showed that dapagliflozin lowers the risk for hHF and subsequently reduces direct medical costs compared to DPP-4i. The protective effect against hHF was more evident among patients with underlying cardiovascular disease.

Efficacy and safety of clopidogrel versus prasugrel and ticagrelor for coronary artery disease treatment in patients with CYP2C19 LoF alleles: a systemic review and meta-analysis.

AIM: We performed a systematic review and meta-analysis to compare the efficacy and safety of ticagrelor and prasugrel with those of clopidogrel in CYP2C19 reduced-metabolizers. METHODS: PubMed, Cochrane and Web of Science were systematically searched for randomized controlled trials or cohort studies up to January 2020. The primary endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, all-cause death, myocardial infarction (MI), stent thrombosis and stroke. The secondary endpoint was bleeding. Pooled effects were measured by relative risk (RR) with 95% confidence intervals (CIs). Publication bias was evaluated with Egger's regression test and adjusted by trim and fill method. RESULTS: Twelve studies comprising 5829 CV patients with CYP2C19 loss-of-function alleles were included. Patients who received ticagrelor or prasugrel showed a lower risk of MACE than those who received clopidogrel (RR 0.524; 95% CI: 0.375, 0.731). The former also had lower risks of CV death (RR 0.409; 95% CI: 0.177, 0.946), all-cause death (RR 0.441; 95% CI: 0.263, 0.739), MI (RR 0.554; 95% CI: 0.414, 0.741) and stent thrombosis (RR 0.587; 95% CI: 0.348, 0.988) than the latter patient group. The risk of stroke was not significantly different between patients receiving the alternatives and those receiving clopidogrel (RR 0.605; 95% CI: 0.257, 1.425). Major and minor bleeding risk was not significantly different between patients treated with alternatives and clopidogrel (RR 1.019; 95% CI: 0.827, 1.260 and RR 1.235; 95% CI: 0.581, 2.628, respectively). CONCLUSION: CYP2C19 reduced-metabolizers can expect better clinical outcome on using prasugrel or ticagrelor rather than clopidogrel.

Dipeptidyl peptidase-4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: A nationwide population-based cohort study.

AIMS: To evaluate the real-world effect of dipeptidyl peptidase-4 inhibitor (DPP4i) on the incidence of autoimmune diseases (AD), including rheumatoid arthritis (RA), inflammatory bowel diseases, multiple sclerosis and systemic lupus erythematosus. METHODS: We identified new users of DPP4i (n = 497 619) or non-DPP4i (n = 643 165) oral combination therapy between 1 January 2011 and 30 June 2015 among patients with type 2 diabetes mellitus in the Korean national health insurance claims database. Patients were followed from the date of initiation of combination therapy until AD outcome, censoring for treatment discontinuation or switching, death or end of study (31 August 2016). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for RA, inflammatory bowel diseases, other AD (multiple sclerosis and systemic lupus erythematosus), and the composite of all outcomes were estimated using propensity score (PS)-adjusted Cox model. RESULTS: In the PS-weighted and PS-matched analysis, the risk of incident RA was decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.67 [95% CI 0.49-0.92] and aHR 0.72 [95% CI 0.51-1.01], respectively). In both analyses, the risk of incident composite AD was also decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.82 [95% CI 0.68-0.99] and aHR 0.76 [95% CI 0.62-0.93], respectively). CONCLUSIONS: In this large population-based cohort study, upfront DPP4i combination therapy was associated with a lower risk of composite AD compared with initial non-DPP4i combination therapy.

Smartphone addiction risk and daytime sleepiness in Korean adolescents.

AIM: Smartphone overuse can cause not only mobility problems in the wrists, fingers and neck but also interference with sleep habits. However, research on smartphone addiction and sleep disturbances is scarce. Therefore, we aimed to investigate daytime sleepiness in association with smartphone addiction risk in Korean adolescents. METHODS: A cross-sectional survey method was used in this study. The Pediatric Daytime Sleepiness Scale was used to assess daytime sleepiness, and the Korean Smartphone Addiction Proneness Scale index was used to evaluate the degree of risk for smartphone addiction. RESULTS: The analyses were performed in 1796 adolescents using smartphones, including 820 boys and 976 girls. The at-risk smartphone users made up 15.1% of boys and 23.9% of girls. Our multivariate analyses demonstrated that students who were female, consumed alcohol, had lower academic performance, did not feel refreshed in the morning and initiated sleep after 12 am were at a significantly higher risk of smartphone addiction. The at-risk smartphone user group was independently associated with the upper quartile Pediatric Daytime Sleepiness Scale score in students with the following factors: Female gender, alcohol consumption, poor self-perceived health level, initiating sleep after 12 am, longer time taken to fall asleep and duration of night sleep less than 6 h. CONCLUSIONS: The quality of sleep in adolescence affects growth, emotional stability and learning skills. Therefore, the management of smartphone addiction seems to be essential for proper sleeping habits. There is a critical need to develop a means of preventing smartphone addiction on a social level.

New initiatives for pharmacovigilance in South Korea: introducing the Korea Institute of Drug Safety and Risk Management (KIDS).

PURPOSE: Pharmacovigilance plays a vital role in ensuring that patients receive appropriate medical products that are safe and effective. This paper aims to describe the history of pharmacovigilance in Korea and introduce the establishment and goal of the KIDS. METHODS: In Korea, the adverse drug reactions (ADR) reporting system was launched in 1988 by the Korea Ministry of Food and Drug Safety (MFDS) and spontaneous ADR reports have been collected from health care professionals and the general public. Although the ADR reporting system has begun, the reporting rate was very low in the first 10 years, and safety actions were done passively in response to the US Food and Drug Administration (FDA) or European Medicines Agency (EMA)'s safety alert and communications. RESULTS: Therefore, the Korea Institute of Drug Safety and Risk Management (KIDS) was established in April 2012 as a new initiative for pharmacovigilance. CONCLUSIONS: The KIDS will continue to contribute to the improvement of Korean pharmacovigilance by collecting, managing, and analyzing consumer-centered drug safety information.

Utilization patterns of disease-modifying antirheumatic drugs in elderly rheumatoid arthritis patients.

This study was conducted to investigate disease-modifying antirheumatic drug (DMARD) utilization in Korean elderly patients with rheumatoid arthritis (RA). We used data from January 1, 2005 to June 30, 2006 from the Health Insurance Review and Assessment Service claims database. The study subjects were defined as patients aged 65 yr or older with at least two claims with a diagnosis of RA. DMARD use was compared by the patients' age-group, gender, medical service, and geographic divisions. The patterns of DMARD use in mono- and combination therapy were calculated. RA medication use was calculated by the number of defined daily doses (DDD)/1,000 patients/day. A total of 166,388 patients were identified during the study period. DMARD use in RA patients was 12.0%. The proportion of DMARD use was higher in the younger elderly, females, and patients treated in big cities. Hydroxychloroquine was the most commonly used DMARD in monotherapy, and most of the combination therapies prescribed it with methotrexate. DMARD use in elderly RA patients was noticeably low, although drug prescriptions showed an increasing trend during the study period, clinicians may need to pay more attention to elderly RA patients.

Comparison of the safety of seven iodinated contrast media.

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.

Utilization of evidence-based treatment in elderly patients with chronic heart failure: using Korean Health Insurance claims database.

BACKGROUND: Chronic heart failure accounts for a great deal of the morbidity and mortality in the aging population. Evidence-based treatments include angiotensin-2 receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, and aldosterone antagonists. Underutilization of these treatments in heart failure patients were frequently reported, which could lead to increase morbidity and mortality. The aim of this study was to evaluate the utilization of evidence-based treatments and their related factors for elderly patients with chronic heart failure. METHODS: This is retrospective observational study using the Korean National Health Insurance claims database. We identified prescription of evidence based treatment to elderly patients who had been hospitalized for chronic heart failure between January 1, 2005, and June 30, 2006. RESULTS: Among the 28,922 elderly patients with chronic heart failure, beta-blockers were prescribed to 31.5%, and ACE-I or ARBs were prescribed to 54.7% of the total population. Multivariable logistic regression analyses revealed that the prescription from outpatient clinic (prevalent ratio, 4.02, 95% CI 3.31-4.72), specialty of the healthcare providers (prevalent ratio, 1.26, 95% CI, 1.12-1.54), residence in urban (prevalent ratio, 1.37, 95% CI, 1.23-1.52) and admission to tertiary hospital (prevalent ratio, 2.07, 95% CI, 1.85-2.31) were important factors associated with treatment underutilization. Patients not given evidence-based treatment were more likely to experience dementia, reside in rural areas, and have less-specialized healthcare providers and were less likely to have coexisting cardiovascular diseases or concomitant medications than patients in the evidence-based treatment group. CONCLUSIONS: Healthcare system factors, such as hospital type, healthcare provider factors, such as specialty, and patient factors, such as comorbid cardiovascular disease, systemic disease with concomitant medications, together influence the underutilization of evidence-based pharmacologic treatment for patients with heart failure.

Thiazolidinedione use in elderly patients with type 2 diabetes: with and without heart failure.

PURPOSE: To compare the prescribing patterns of thiazolidinediones (TZDs) in elderly patients with type 2 diabetes with and without heart failure (HF). METHODS: The national health insurance claims database from the Health Insurance Review & Assessment Service (HIRA), Korea was used. Elderly patients with type 2 diabetes taking at least one hypoglycemic agent were studied between July 1, 2005 and June 30, 2006. Patients were grouped according to the presence of HF. The proportion of patients receiving TZDs were compared between the two groups, and stratified by their diabetes medication regimen (monotherapy and combination therapy). The difference in the patterns of TZD prescribed was studied across all health care levels including: primary, secondary, and tertiary care facilities. RESULTS: Among 357,855 elderly patients with type 2 diabetes, 24,746 patients had HF. TZDs were prescribed to 10.4% of the patients with HF and 8.8% of the patients without HF (p < 0.01). In the combination therapy group, the proportion of patients receiving TZDs was 17.9% and 14.4% in patients with and without HF, respectively (p < 0.01). In the primary care setting, the proportion of TZD prescriptions in patients with HF was 5.6% and it was 4.6% in patients without HF (p < 0.01). CONCLUSIONS: TZDs were frequently prescribed to patients with HF, even though the TZDs were contraindicated in patients with HF. Health care professionals should consider alternative therapies for patients with type 2 diabetes mellitus. In addition, they should carefully monitor the impact of TZD use in patients with HF.

Overlapping medication associated with healthcare switching among Korean elderly diabetic patients.

This study was performed to describe the patterns of healthcare switching with overlapping use of anti-diabetic medication in the elderly using the Korea Health Insurance Review and Assessment Service's claims data. The study subjects were ambulatory elderly diabetic patients (ICD-10, E10-14) receiving at least one oral anti-diabetic drug or insulin, and visiting healthcare facilities more than two times between January and December 2005. A total of 457,975 elderly diabetic ambulatory care patients were identified. The mean of visiting frequencies was 9.0 ( ± 3.6) and switching frequencies was 1.5 ( ± 0.8) during 2005. Switching group consisted of 33% of total study subject. Healthcare switching was common in female patients who were older, and had treated polytherapy more in rural areas. The movement among primary care medical services was very common among the patients in the switching group (52.6%). A statistically significant correlation was observed between the healthcare switching and concomitant drug use (rho = 0.96), and overlapping days (rho = 0.57). The use of overlapping anti-diabetic medication increased with the extent of healthcare switching. Further, frequent switching of healthcare between primary clinics was observed. Efforts should be made to establish continuity for the elderly diabetic patients with the identification of frequent switching with overlapping medication.

Risk of Cardiovascular Events and Medical Cost of Dapagliflozin and Dipeptidyl Peptidase-4 Inhibitors.

This study compared dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, and dipeptidyl peptidase-4 inhibitors (DPP-4i) with regard to cardiovascular (CV) event incidence and direct medical costs during type 2 diabetes treatment. A retrospective cohort study was conducted using national health insurance claims data from September 1, 2014, to June 30, 2018, of patients in Korea. Patients who were prescribed dapagliflozin and DPP-4i for the first time were included. The primary outcome was the incidence of a composite of major adverse CV events (MACEs)-nonfatal myocardial infarction, nonfatal stroke, or in-hospital CV death. Proportional hazard models after propensity score weighting were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE in the dapagliflozin and DPP-4i groups. A decision analytic model was used to compare direct medical costs between the two treatment groups from a healthcare provider's perspective. Of the 260,336 patients in the cohort, 23,147 and 237,189 received dapagliflozin and DPP-4i, respectively. During the follow-up, 184 patients receiving dapagliflozin and 3,674 receiving DPP-4i (incidence, 6.47 and 11.33 events/1,000 person-years, respectively) had MACE. The adjusted HR of MACE for dapagliflozin compared with that for DPP-4i was 0.69 (95% CI 0.57-0.83). The corresponding HRs were consistent among patients with and without underlying CV disease. The estimated direct medical cost appeared to be lower by $68,452 in the dapagliflozin group than that in the DPP-4i group for 3 years, in 1,000 hypothetical patients. In this population-based cohort study, the use of dapagliflozin instead of DPP-4i was associated with a reduced risk of MACE, which subsequently reduced direct medical costs. These data provide valuable information to patients, practitioners, and authorities regarding the risk of CV events associated with dapagliflozin versus DPP-4i use in clinical practice.

Genotype-guided warfarin dosing may benefit patients with mechanical aortic valve replacements: randomized controlled study.

This prospective, single-blind, randomized study was designed to evaluate the effect of genotype-based warfarin dosing compared with standard warfarin dosing in Korean patients with mechanical cardiac valves. Patients were assigned to either the genotype-based dosing group or the standard dosing group using stratified block randomization. The genotype-based dosing equation was adopted from a previous study which included VKORC1 rs9934438, CYP2C9 rs1057910, CYP4F2 rs2108622, and age. Primary outcomes included the percentage of time in the therapeutic range (pTTR): (i) during the first week following initiation of warfarin therapy, (ii) during hospitalization and (iii) until the first outpatient visit. A total of 91 patients were included in the analysis, 42 treated with genotype-based warfarin dosing and 49 treated with standard warfarin dosing. The genotype frequency differences of the three SNPs included in this study (ie, VKORC1, CYP2C9, CYP4F2), between the genotype-based dosing and standard dosing groups were not different. The genotype-based dosing group trended toward higher pTTR when compared with the standard dosing group, although this difference was not statistically significant. In patients with aortic valve replacement, TTRTraditional and TTRRosendaal were significantly higher in the genotype-based dosing group when compared with the standard dosing group during the first week following treatment initiation [ie, 58.5% vs. 38.1% (p = 0.009) and 64.0% vs. 44.6% (p = 0.012), respectively]. Based on the results, the genotype-guided dosing did not offer a significant clinical advantage, but a possible benefit in patients with aortic valve replacement has been suggested.

Gonadotropin-releasing hormone agonists, anti-androgens and the risk of cardio-cerebrovascular disease in prostate cancer patients: an asian population-based observational study.

Purpose: To conduct a population-based study to determine whether the use of GnRH agonist and antiandrogens are associated with an increased risk of cardio-cerebrovascular disease (CCVD) in Asian patients with prostate cancer using the National Health Insurance Service-Elderly Cohort Database (NHIS-ECD). Materials and Methods: We included a total of 2,413 men aged 60 years or older with prostate cancer between January 2003 and December 2008. Outcomes of interest included the first occurrence of cardiovascular events [acute myocardial infarction (AMI), ischemic heart disease (IHD)] and cerebrovascular events [ischemic stroke (IS), and cerebrovascular disease (CVD)]. Results: The 5-year AMI-free rates of patients diagnosed with prostate cancer and treated with GnRH agonists, antiandrogens alone, or androgen deprivation therapy (ADT)-naïve interventions were 97.0%, 96.5%, and 98.3%, respectively, while the 5-year IHD-free rates were 93.2%, 92.3%, and 94.5%, respectively. Exposure to GnRH agonists or antiandrogen regimens did not significantly increase the risk of AMI or IHD compared to ADT-naïve treatment in multivariate Cox proportional-hazards models after adjusting for other covariates. Five-year IS-free rates of patients exposed to GnRH agonists, antiandrogens alone, and those with ADT-naïve prostate cancer were 94.8%, 94.7%, and 95.5%, respectively, while the five-year CVD-free rates were 92.9%, 93.3%, and 94.6%, respectively. Cox proportional-hazards models also failed to show that men who received GnRH agonist or antiandrogen treatment alone carried a significantly increased risk for IS or CVD compared to ADT-naïve patients. Conclusions: The current study based on Asian population suggests that treatment with neither GnRH agonist nor antiandrogens increases the risk of cardio-cerebrovascular disease compared to patients with ADT-naïve prostate cancer.

Effects of proton pump inhibitor use on risk of Clostridium difficile infection: a hospital cohort study.

BACKGROUND: Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed studies analyzing the effects of PPI use on CDI risk are lacking. The present study investigated the association of the dose, duration, and types of PPIs with CDI risk. METHODS: A single-center, cohort study was conducted on patients admitted to a hospital. The exposed cohort comprised patients who were prescribed PPIs at least once during the study period, and a control cohort was prepared by randomly assigning an index date to patients who did not use PPIs ensuring the same distribution of index dates as in the exposed cohort and matching sex, age, hospitalization period, and date of admission. RESULTS: PPI use increased the risk of CDI by 1.8-fold [95% confidence interval (CI) 1.5-2.2]. CDI risk increased by 1.8-fold with esomeprazole (95% CI 1.4-2.2) and 2.0-fold with pantoprazole (95% CI 1.5-2.8). Patients who used a high dose had a higher risk than those who used a medium dose [adjusted hazard ratio (HR) 2.0 vs 1.3]. The risk of CDI increased 4.2-fold when the PPI exposure period was 6 days or shorter than 6 days. CONCLUSIONS: Our study showed that PPI use was associated with an increased risk of developing CDI and the risk of CDI was dose dependent. Therefore, PPIs should only be used at proper doses and only for the necessary indications to avoid CDI risk.

Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax.

PURPOSE: Talc slurry (TS) has been commonly used with high success rates in managing spontaneous pneumothroax (SP), but there were concerns of post-procedural complications. Alternatively, doxycycline solution (DS) was used successfully. This retrospective study aims to compare the effectiveness and safety between talc and doxycycline as a sclerosing agent and to investigate risk factors for recurrence in patients with SP. METHODS: The review of medical records between January 2011 and December 2014 was conducted on 83 patients with SP who underwent pleurodesis with either TS (n=16) or DS (n=67). Recurrence and complications were compared between the DS and TS groups. Associations between recurrence after DS treatment and various factors were analysed. RESULTS: Recurrence was significantly higher in the DS group than in the TS group (P=0.033), whereas complications were higher in the TS group than the DS group: fever was significantly higher in the TS group (P=0.001). Recurrences associated with doxycycline use were found significantly more often in patients with recurrent diagnosis of SP, height/weight ≥3.25 cm/kg and weight <55 kg. CONCLUSION: Talc was more effective without recurrence compared with doxycycline. Clinically insignificant fever associated with pleurodesis was more common with talc. Low weight, high height to weight ratio and recurrent diagnosis of SP were associated with higher recurrence after doxycycline treatment.

Outcomes with perioperative fat emulsions containing omega-3 fatty acid: A meta-analysis of randomized controlled trials.

PURPOSE: Results of a meta-analysis of data from clinical studies comparing patient outcomes and hospital length of stay (LOS) in surgical patients receiving fish oil (FO)-containing i.v. fat emulsions (IVFEs) versus non-FO-containing IVFEs are presented. METHODS: Computerized searches of the MEDLINE, Embase, and Coch rane CENTRAL databases were performed in August 2014 to identify English-language articles on randomized controlled trials (RCTs) comparing FO-containing and non-FO-containing IVFEs in adult surgical patients receiving parenteral nutrition. Selected articles were analyzed for methodological and publication bias and study heterogeneity (I2 statistic). RESULTS: Data from 19 RCTs (total n = 1,167) were included in the meta-analysis. Compared with use of non-FO-containing IVFEs (products based in soybean oil [SO], medium-chain triglycerides, or olive oil), use of FO-containing IVFEs was associated with reduced infectious morbidity (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.30-0.65; p < 0.0001; I2 = 0%); the effect size was greatest for FO-containing versus SO-based IVFEs. Relative to use of SO-based IVFEs, use of FO-containing IVFEs was associated with a significant reduction in hospital LOS (weighted mean difference, -2.70 days; 95% CI, -3.60 to -1.79 days; p < 0.00001; I2 = 0%). CONCLUSION: The results of the meta-analysis indicated that FO-containing IVFEs could improve infectious morbidity and LOS. The overall effect of reducing infectious morbidity and LOS was found to be the greatest in comparison with the SO-based IVFEs.

Risk of hospitalization for hypoglycemia among older Korean people with diabetes mellitus: Interactions between treatment modalities and comorbidities.

The objective of this study was to carry out a large population-based study to understand the factors associated with hypoglycemia-related hospitalizations among older Korean adults with diabetes mellitus.This study analyzed data from a subset of the 2013 Health Insurance and Review and Assessment service-Adult Patient Sample. A total of 307,170 subjects, comprising 41.7% men and 58.3% women, had diabetes mellitus. Hypertension (80.8%) was the most common comorbidity, and dyslipidemia (59.0%) and ischemic heart disease (21.3%) were also prevalent. Approximately half of the patients with diabetes had >2 comorbidities, and two-thirds of the patients had >3 comorbidities. The proportion of patients taking insulin or sulfonylureas was 54.9%, and 23.2% of the patients were taking other medications. About 21.9% of the patients were treated nonpharmacologically. A total of 2867 hypoglycemia-related admission occurred, the incident rate was 9.33 per 1000 person. The risk was higher among female patients and older patients with several comorbidities, including cardiovascular disease, cerebrovascular disease, chronic liver disease, chronic kidney disease, dementia, and malignancies. Treatment modalities, including insulin and sulfonylureas, were associated with a high risk of hypoglycemia. After adjustments for age, sex, the different comorbidities, and the treatment modalities, we determined that chronic kidney disease and dementia were associated with a high risk of hypoglycemia-related hospitalization (odds ratio [OR] = 2.52 and OR = 1.93, respectively). Furthermore, patients with chronic kidney disease or dementia who were treated with sulfonylureas and insulin had very high risks of hypoglycemia, and the incident rate was 66.6 and 63.75 per 1000 person, respectively.In conclusion, the presence of comorbidities, especially chronic kidney disease and dementia, increased the risk of hypoglycemia-associated hospitalization within this population of older patients with diabetes. The impact of the treatment modality, for example, insulin or sulfonylureas, on hypoglycemia was much greater among these patients.

INR optimization based on stroke risk factors in patients with non-valvular atrial fibrillation.

BACKGROUND: Bleeding complications have been frequently reported in East Asian patients on warfarin with a target international normalized ratio (INR) of 2.0-3.0. OBJECTIVE: This study aimed to identify the optimal therapeutic range of the INR in Korean patients with non-valvular atrial fibrillation (NVAF). Setting Cardiovascular department of a 1320 inpatient bed Korean hospital. METHOD: Retrospective chart review was conducted on 1014 patients for a total follow-up period of 2249.2 patient years. Major thromboembolic and bleeding complications were evaluated. The INR incidence of complication curve was plotted, and the optimal therapeutic range of INR was determined from the intersection of curves to ensure the lowest incidences of both thromboembolic and bleeding complications. For subgroup analysis, all patients were stratified by the following factors: age (above 75), disease (presence of hypertension, diabetes, congestive heart failure, and a history of stroke or thromboembolism), rhythm control procedure, and concurrent aspirin therapy. Main outcome measure Optimal therapeutic ranges of INR according to the risk factors. RESULTS: A total of 41 thromboembolic and 91 bleeding events occurred during the follow-up period. The complication rates were the lowest at an INR of 1.9 and the optimal therapeutic range was estimated to be 1.7-2.2 for the overall patients. The optimal therapeutic ranges of INR in the stratified patients were determined as follows: 1.3-1.8 in the patients ≥75 years of age; 1.5-2.0 in patients with hypertension, diabetes and concurrent aspirin therapy; 1.8-2.3 in patients with congestive heart failure; 1.9-2.4 in patients with previous stroke or thromboembolism; 1.7-2.2 in patients who had undergone rhythm control procedures. It has been shown that, by keeping the INR within these ranges, complication risks could be significantly reduced by up to 81 %. CONCLUSION: The intensity of anticoagulation therapy for Korean patients with NVAF is optimal when INR is between 1.7 and 2.2.

Drug persistency of cholinesterase inhibitors for patients with dementia of Alzheimer type in Korea.

This study examined 1-year persistency with cholinesterase inhibitors (ChEIs) for the treatment of elderly Alzheimer's dementia (AD) patients in Korea. Korean Health Insurance Review & Assessment Service database from January 2005 to June 2006 was used. Patients aged 65 or older with AD diagnosis who were first prescribed a ChEI were included. The 1-year persistence, persistency rate, and switching patterns during the follow-up period were identified. Mean time to drug discontinuation was analyzed, and persistency rates between different patient factors were compared. The 1-year persistency rate of newly treated 6,461 AD patients was 24.0%, while 50% of study patients discontinued treatment by 91 days from initiation. Persistency rates of female patients (22.8%), patients in rural areas (12.7%), and primary care (10.2%) were relatively low (p < 0.001). Persistency rate differed between age groups (p < 0.001). Overall proportion of switching was 6.6%. The 1-year persistency rate of ChEIs for AD patients in Korea did not reach those of previous researches in other countries. Patients less likely to remain on therapy should be especially monitored to optimize treatment persistence.

Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study.

BACKGROUND/OBJECTIVES: Data on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin. METHODS: We conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards model weighted for a propensity score. RESULTS: During follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI) for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81 (0.67-0.99), respectively. CONCLUSIONS: Compared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.