Iyn-Hyang Lee

Underutilization of warfarin for stroke prophylaxis in patients with atrial fibrillation or atrial flutter in Korea

OBJECTIVE Anticoagulation therapy with warfarin is recommended for stroke prevention in patients with atrial fibrillation (AF) or atrial flutter (AFL) whose risks for stroke are high. However, previous studies suggest that warfarin is markedly underused. This study aims to investigate the incidence and risk factors of warfarin underutilization in patients with high risk of stroke in Korea. METHODS This was a cross-sectional study using the data of 2009 from National Patients Sample compiled by the Health Insurance Review and Assessment Service. Patients with high risk of thromboembolism were identified with congestive heart failure, hypertension, age ≥75 years, diabetes, and prior stroke (CHADS2) score ≥2. High-risk patients of bleeding were excluded using Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) score >4. Warfarin and antithrombotic therapy underutilization were defined and estimated in high-risk patients. Any demographic and clinical factors associated with warfarin and antithrombotic therapy underutilization were explored using a logistic regression model. RESULTS Of the national patient sample, 15,885 patients were identified with AF or AFL. Among them, a total of 8475 patients who had an admission history, CHADS2 ≥2, and ATRIA score ≤4 were included in the analysis. From the study sample, warfarin underutilization and antithrombotic therapy underutilization were estimated to be 64.0% and 20.4%, respectively. Predictors of warfarin underutilization include female sex, age ≥80 years, lower CHADS2 score, and insurance type (Medical Aid program). CONCLUSIONS A high portion of AF/AFL patients with CHADS2 score ≥2 were undertreated with warfarin. As ischemic stroke is one of the leading causes of death in Korea, a more aggressive approach to prevent stroke in patients with AF/AFL is required.

International experience in controlling pharmaceutical expenditure: influencing patients and providers and regulating industry – a systematic review

Objective To review international policies to control expenditure on pharmaceuticals by influencing the behaviour of patients and providers and regulating the pharmaceutical industry. Method Systematic review of experimental and quasi-experimental studies. Published studies were identified with an electronic search strategy using MEDLINE and EMBASE from 1980 to May 2012. Studies were eligible if they assessed the effect of policies aimed at influencing the behaviour of patients and providers, and regulating the pharmaceutical industry. Outcome measures included pharmaceutical expenditure, prices or utilization; other resource use relating to pharmaceuticals; and health outcomes and patients’ or providers’ behaviour relating to pharmaceutical use. Quality assessment criteria for each study design were developed based on the standard criteria recommended by the Cochrane Effective Practice and Organisation of Care (EPOC) group. The review includes studies based on randomized controlled trials and rigorous quasi-experimental designs (interrupted time-series and controlled before-and-after studies). Studies were excluded if they were conducted within a single hospital or practice; related to pharmaceutical care services or disease management; had less than 6 months of follow-up period (or less than 12 months overall for interrupted time series); if data in controlled before-and-after studies were not collected contemporaneously or if no rationale was stated for the choice of control group; or if relevant and interpretable data were not presented. Results A total of 255 studies met the inclusion criteria for this review. The majority of the studies relating to patients evaluated cost sharing interventions such as user charges (52 studies). User charges do reduce utilization of pharmaceuticals, and reduce public expenditure by shifting costs to patients. But they reduce the use of essential as well as non-essential drugs, and without adequate exemptions they affect vulnerable groups disproportionately. The majority of studies relating to doctors evaluated the effects of educational approaches (78 studies), reimbursement restrictions (48 studies) and incentive systems (22 studies). Evidence on these policies is of mixed quality. It appears possible to influence prescribing modestly, through various means, but it is essential that messages to prescribers are based on good evidence of effectiveness and cost-effectiveness. Twenty-nine studies related to industry regulation, and they were of mixed quality. Evidence from studies of reference pricing suggests that this may result in cost savings. These are, however, achieved not by companies reducing or restraining prices, or by reductions in the overall volume of prescriptions, but by some shifts in use and shifting costs to patients, with consequent adverse effects on the equity of access to medicines. Other price and profit controls remain almost completely lacking in evaluative evidence. Conclusions It may be that the undesirable consequences of policies influencing patients, particularly user charges, can outweigh the benefits. To influence demand for pharmaceuticals, it is more appropriate to influence prescribing doctors and although interventions to improve prescribing practice have been developed, they often achieve relatively modest benefits and sometimes at high cost. Good evaluative evidence related to industry regulation is scarce despite its policy importance.

Satisfaction and expressed needs of pharmaceutical care services and challenges recognized by patients in South Korea

Purpose To assess the degree of satisfaction and expressed needs of pharmaceutical care services in patients with chronic diseases and explore the factors related to the needs from patients’ perspectives for the further development of pharmaceutical care service models. Patients and methods A cross-sectional survey of 220 patients (mean age ± SD: 61.3±13.1, male:female: 104:116) was conducted. The questionnaire was structured to measure patients’ degree of satisfaction and expressed needs using a 5-point Likert scale. Additionally, preferred duration, methods of service delivery, and willingness to pay were surveyed. Responses were analyzed using an ordinal regression method to predict factors that were related to pharmaceutical care services. Results Sixty-seven patients had experienced pharmaceutical care services. Their satisfaction levels were high in all categories; however, there were no significant differences between categories. The levels of expressed needs were similar among categories without significant differences. The preferred delivery method was a face-to-face conversation combined with being provided with written information (53.2%). The preferred duration was ≤10 min (70.5%). About 48% of the patients showed willingness to pay for the service. Education level and region influenced patients’ needs. Conclusion The satisfaction and needs of pharmaceutical care services was very positive; however, noticing only a third of patients experienced pharmaceutical care services, this may indicate a lack of awareness and less appreciation of pharmacists by patients. Details concerning patients’ awareness and the value of pharmaceutical care services require further investigation.

Perceived needs of pharmaceutical care services among healthcare professionals in South Korea: a qualitative study

Purpose To explore the need for pharmaceutical care services, key features of desirable pharmacy services, and perceived barriers for advancing the services in hospital environments with doctors and nurses who are key co-workers of the interdisciplinary team care services.Methods Semi-structured, in-depth interviews with eighteen doctors and fifteen nurses employing purposive and snowballing sampling strategies were conducted in ten hospitals in South Korea. Results The level of pharmaceutical care was varied across regions or institutions in South Korea. The concept of pharmaceutical care was insufficiently defined, and tended to be limited to some parts of medication counseling. Through pharmaceutical care services, doctors desired to acquire comprehensive drug information from and to share clinical responsibilities with pharmacists. Nurses wished to lower their burdens of medication counseling services from their daily practices. Doctors and nurses asked for pharmacists providing essential and carefully selected medication information to their patients in a patient-centered manner. The listed barriers to pharmaceutical care included the lack of appropriate systems for reward, insufficient accessibility to patient records by pharmacists, ambiguous role descriptions of pharmacist, and absence of effective communication among professionals. Conclusion A successful pharmaceutical care service model should allow efficient exchange of information among healthcare professionals to build inter-professional trust and to provide a continuity of care both in terms of time and setting. As prerequisites of such system, it was warranted to develop clinical evidence and an appropriate reward system for pharmaceutical care services.

Inadequate stroke prevention in Korean atrial fibrillation patients in the post-warfarin era

BACKGROUND Anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is recommended for atrial fibrillation (AF) patients who are at a high risk for stroke. This study aimed to investigate the utilization of anticoagulants since the introduction of DOACs in South Korea. METHODS This was a cross-sectional study using claim-based national data from 2011 to 2014 derived from the Aged Patient Sample (APS) compiled by the Health Insurance Review & Assessment Service (HIRA). Patients with a high risk for thromboembolism were identified as those having a CHA2DS2-VASc (congestive heart failure, hypertension, age≥75, diabetes mellitus, stroke (or transient ischemic attack), vascular disease, sex) score of ≥2. Patients at a high risk for bleeding with an ATRIA (anticoagulation and risk factors in atrial fibrillation) bleeding score of >4 were excluded. Anticoagulant underutilization was estimated in these high-risk patients. Demographic and clinical factors associated with warfarin and DOAC underutilization were explored using a logistic regression model. RESULTS Anticoagulant underutilization among high-risk patients for stroke decreased from 68% to 62.5% between 2011 and 2014; however, there was further scope for improvement. The risk factors for underutilization were identified as follows: female sex, old age, having medical aid insurance, presence of vascular disease, and limited anticoagulant options. CONCLUSIONS Our study demonstrates that a large population of AF patients in South Korea failed to obtain adequate stroke prevention treatment, even in the era of DOAC usage. A more aggressive approach to provide optimal antithrombotic therapy is warranted.

Pharmaceutical Pricing Policies in South Korea

South Korean healthcare system has experienced an unprecedented growth and transformation in the span 15 years. The landmarks were the unification of insurance funds, and the separation of prescribing and dispensing of drugs (SPD). Several pricing policies have been introduced, revised and abolished to attempt to address unexpected increases in pharmaceutical expenditure which followed the separation of prescribing and dispensing of medicines. This chapter outlines the health care and pharmaceutical systems in South Korea, details pricing policies in the latest decade and reviews the effectiveness of these policies. While having a long-lasting history in pharmaceutical price control, South Korea has often introduced policies with a weak scientific basis and then abolished them without proper assessment and evaluation. Some evidence suggests that price controls have reduced pharmaceutical costs in the short-term, but evidence on the long-term impacts are largely absent. Given the cause of current cost inflation, i.e., increased use of pharmaceuticals and an ageing population, society needs a policy consensus to control prices and encourage rational prescribing.

Awareness and attitude of the public toward personalized medicine in Korea

Objectives As personalized medicine (PM) is expected to greatly improve health outcomes, efforts have recently been made for its clinical implementation in Korea. We aimed to evaluate public awareness and attitude regarding PM. Methods We performed a self-administered questionnaire survey to 703 adults, who participated in the survey on a voluntary basis. The primary outcome measures included public knowledge, attitude, and acceptance of PM. We conducted multinomial multivariate logistic analysis for outcome variables with three response categories and performed multivariate logistic regression analyses for dichotomous outcome variables. Results Only 28% of participants had knowledge that genetic factors can contribute to inter-individual variations in drug response and the definition of PM (199 out of 702). Higher family income was correlated with greater knowledge concerning PM (OR = 3.76, p = 0.034). A majority of respondents preferred integrated pharmacogenomic testing over drug-specific testing and agreed to inclusion of pharmacogenomic testing in the national health examination (64% and 77%, respectively), but only 51% were willing to pay for it. Discussion Our results identify the urgent need for public education as well as the potential health disparities in access to PM. This study helps to frame policies for implementing PM in clinical practice.

Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells

Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17-28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 μM concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17-28 may be a lead compound to develop AMD therapeutics.

Antitumor activity of BJ-1207, a 6-amino-2,4,5-trimethylpyridin-3-ol derivative, in human lung cancer

Enhanced expression of NADPH oxidase (NOX) and the subsequent production of reactive oxygen species (ROS) are associated with lung cancer. In the present study, fifty 6-amino-2,4,5-trimethylpyridin-3-ol derivatives were screened for anticancer activity by targeting NOX2-derived ROS. The compounds suppressed ROS production and decreased cancer cell viability (R2 = 0.79). Among the derivatives, the compound coded BJ-1207, which contained a 4-(hydroxydiphenylmethyl)piperidine moiety, exhibited the most effective anticancer activity against A549 lung cancer cell line and eight other cancer cell lines, including H1299, MCF-7, MDA-MB-231, HT-29, SW620, Mia PaCa-2, PANC-1, and U937. BJ-1207 also showed significantly lower inhibitory effects on kinase insert domain receptor (KDR) and c-KIT tyrosine kinase but higher inhibitory activity on NOX than those of sunitinib, a multi-receptor tyrosine kinase (RTK) inhibitor. In addition, BJ-1207-induced inhibition of RTK-downstream signaling pathways, such as ROS production, and expression of target genes, such as stem cell factor and transforming growth factor-α, were similar to those induced by sunitinib. In the xenograft chick tumor model, BJ-1207 inhibited lung tumor growth to a similar or much greater extent than that of sunitinib or cisplatin, respectively. Overall, the present study showed that BJ-1207, a vitamin B6-derived 2,4,5-trimethylpyridin-3-ol compound with azacyclonol moiety at C (6)-position of the pyridine ring, inhibited NOX activity and that it is a promising lead compound for developing anticancer drugs against lung cancer.

Effects of a price cut reform on the cost and utilization of antidiabetic drugs in Korea: a national health insurance database study

BackgroundDespite the potential widespread application and a significant need, the policy effectiveness of prescribed medications price controls has not been studied extensively. We aimed to explore the effects of a price cut introduced in April 1st of 2012 on the cost and utilization of antidiabetics in South Korea.MethodsWe identified approximately four million outpatients who filed at least one diabetes-related claim during the index period (January 2010 to December 2012) using the National Health Insurance claims data. We performed interrupted time series analyses for cost and utilization of “overall,” “reduced price,” and “constant price” antidiabetics between January 2009 and June 2013, and measured the growth rate for incidents of medical and surgical procedures for diabetes-induced complications.ResultsThe segmented regression suggests that spending on overall and reduced price antidiabetics would drop by 6 and 23%, respectively; spending on constant price antidiabetics would rise by 16% in a year after the new pricing compared to if the policy were not in existence. There were a few immediate changes in utilization, and its trend indicated a significant decrease in reduced price antidiabetics and an increase in constant price antidiabetics. Incidents of medical and surgical procedures relating to diabetic complications were unaffected.ConclusionsThe Korean price cut program contained costs by immediately reducing the cost of pharmaceuticals without any major signals associated with compromised clinical conditions in diabetic patients.