Sooyoung Shin

Evaluation of costs accrued through inadvertent continuation of hospital-initiated proton pump inhibitor therapy for stress ulcer prophylaxis beyond hospital discharge: a retrospective chart review

Background Stress ulcers and related upper gastrointestinal bleeding are well-known complications in intensive care unit (ICU) patients. Proton pump inhibitor (PPI)-based stress ulcer prophylaxis (SUP) has been widely prescribed in noncritically ill patients who are at low risk for clinically significant bleeding, which is then injudiciously continued after hospital discharge. This study aimed to evaluate the incidence of inappropriate prescribing of PPI-based preventative therapy in ICU versus non-ICU patients that subsequently continued postdischarge, and to estimate the costs incurred by the unwarranted outpatient continuation of PPI therapy. Methods A retrospective review of patient data at a major teaching hospital in Korea was performed. During the 4-year study period, adult patients who were newly initiated on PPI-based SUP during hospital admission and subsequently discharged on a PPI without a medical indication for such therapy were captured for data analysis. The incidence rates of inappropriate prescribing of PPIs were compared between ICU and non-ICU patients, and the costs associated with such therapy were also examined. Results A total of 4,410 patients, more than half of the inpatient-initiated PPI users, were deemed to have been inadvertently prescribed a PPI at discharge in the absence of a medical need for acid suppression. The incidence of inappropriate outpatient continuation of the prophylaxis was higher among ICU patients compared with non-ICU patients (57.7% versus 52.2%, respectively; P=0.001). The total expenditure accrued through the continuation of nonindicated PPI therapy was approximately US

Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database.

40,175. Conclusion This study confirmed that excess usage of PPIs for SUP has spread to low-risk, non-ICU patients. The overuse of unwarranted PPI therapy can incur large health care expenditure, as well as clinical complications with minimal therapeutic benefits. Educating clinicians regarding SUP guidelines and the adverse effects of long-term use of acid suppression can improve the cost effectiveness of PPI therapy.

Niacin as a drug repositioning candidate for hyperphosphatemia management in dialysis patients

Background/Objectives Addition of cilostazol or sarpogrelate to the standard dual antiplatelet therapy of aspirin and clopidogrel has been implemented in patients that underwent percutaneous coronary intervention (PCI) with stents in Korea. This study aimed to evaluate the efficacy and safety of triple antiplatelet therapies. Methods This retrospective cohort study was performed using the Korean National Insurance Claim Data of the Health Insurance Review and Assessment Service from January 1, 2009 to December 31, 2014. The study cohort population consisted of patients with ischemic heart diseases and a history of PCI. They were treated with antiplatelet therapy of aspirin, clopidogrel (AC); aspirin, clopidogrel, cilostazol (ACCi); or aspirin, clopidogrel, sarpogrelate (ACSa) during the index period from January 1, 2010 to December 31, 2011. During the follow-up period up to December 31, 2014, the major adverse cardiac or cerebral events (MACCE) including death, myocardial infarction, target lesion revascularization, and ischemic stroke were assessed. Bleeding complications were also evaluated as adverse drug events. Results Out of 93,876 patients with PCI during the index period, 69,491 patients started dual (AC) or triple therapy (ACSa or ACCi). The clinical outcomes of comparing ACSa and ACCi therapy showed beneficial effects in the ACSa group in the prevention of subsequent cardiac or cerebral events. After Propensity score-matching between ACSa and ACCi groups, there were significant differences in MI and revascularization, with corresponding HR of 0.38 (95% CI, 0.20–0.73) and 0.66 (95% CI, 0.53–0.82) in ACSa vs. ACCi at 12 months, respectively. At the 24-month follow-up, the triple therapy groups (ACS or ACC) had a higher incidence of MACCE compared to the dual therapy (AC) group; ACSa vs. AC HR of 1.69 (95% CI, 1.62–1.77); ACC vs. AC HR of 1.22 (95% CI, 1.06–1.41). There was no significant difference in severe or life-threatening bleeding risk among three groups; ACSa vs. AC, HR of 0.68 (95% CI, 0.37–1.24), ACCi vs. AC, HR of 0.91 (95% CI, 0.77–1.09). Conclusion Sarpogrelate-containing triple antiplatelet therapy demonstrated comparable rates of MACCE prevention to the conventional dual antiplatelet therapy after PCI without significantly increasing bleeding risk during the two-year follow-up period.

Impact of statins on risk of new onset diabetes mellitus: a population-based cohort study using the Korean National Health Insurance claims database

Nearly all patients with end-stage renal disease develop hyperphosphatemia. These patients typically require oral phosphate binders for life-long phosphorus management, in addition to dietary restrictions and maintenance dialysis. Recently, niacin, a traditional antilipemic agent, drew attention as an experimental treatment for hyperphosphatemia. The purpose of this article was to report on new findings regarding niacin’s novel effects and to review the possibility of repurposing niacin for hyperphosphatemia treatment in dialysis patients by elucidating its safety and efficacy profiles along with its synergistic clinical benefits. Following approval from the Institutional Review Board, we tracked the yearly trends of order frequency of niacin in comparison with statins and sevelamer in a tertiary care hospital. Also, a Cochrane Library and PubMed literature search was performed to capture prospective clinical trials on niacin’s hypophosphatemic effects in dialysis patients. Niacin use in clinical settings has been on the wane, and the major contribution to that originates from the wide use of statins. Niacin use rates have further plummeted following a trial failure which prompted the suspension of the niacin-laropiprant (a flushing blocker) combination product in the global market. Our literature search identified ten relevant articles. Overall, all studies demonstrated that niacin or nicotinamide (the metabolite form) reduced serum phosphorus levels as well as Ca-P products significantly. Additive beneficial effects on lipid parameters were also observed. Sevelamer appeared superior to niacin in a comparative study, but the study design had several limitations. The intervention dosage for niacin ranged from 375 to 1,500 mg/day, with the average daily dose of approximately 1,000–1,500 mg. Niacin can be a patient-convenient and inexpensive alternative or adjunctive therapy for phosphorus management in dialysis patients. Further well-designed, large-scale, long-term, comparative trials are needed to successfully repurpose niacin for the new indication.

Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

Statin therapy is beneficial in reducing cardiovascular events and mortalities in patients with atherosclerotic cardiovascular diseases. Yet, there have been concerns of increased risk of diabetes with statin use. This study was aimed to evaluate the association between statins and new onset diabetes mellitus (NODM) in patients with ischemic heart disease (IHD) utilizing the Korean Health Insurance Review and Assessment Service claims database. Among adult patients with preexisting IHD, new statin users and matched nonstatin users were identified on a 1:1 ratio using proportionate stratified random sampling by sex and age. They were subsequently propensity score matched further with age and comorbidities to reduce the selection bias. Overall incidence rates, cumulative rates and hazard ratios (HRs) between statin use and occurrence of NODM were estimated. The subgroup analyses were performed according to sex, age groups, and the individual agents and intensities of statins. A total of 156,360 patients (94,370 in the statin users and 61,990 in the nonstatin users) were included in the analysis. The incidence rates of NODM were 7.8% and 4.8% in the statin users and nonstatin users, respectively. The risk of NODM was higher among statin users (crude HR 2.01, 95% confidence interval [CI] 1.93–2.10; adjusted HR 1.84, 95% CI 1.63–2.09). Pravastatin had the lowest risk (adjusted HR 1.54, 95% CI 1.32–1.81) while those who were exposed to more than one statin were at the highest risk of NODM (adjusted HR 2.17, 95% CI 1.93–2.37). It has been concluded that all statins are associated with the risk of NODM in patients with IHD, and it is believed that our study would contribute to a better understanding of statin and NODM association by analyzing statin use in the real-world setting. Periodic screening and monitoring for diabetes are warranted during prolonged statin therapy in patients with IHD.

Impact of clinical evidence communications and drug regulation changes concerning rosiglitazone on prescribing patterns of antidiabetic therapies

Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.

The effect of sitagliptin on cardiovascular risk profile in Korean patients with type 2 diabetes mellitus: a retrospective cohort study

Cardiovascular safety alerts about rosiglitazone resulted in regulatory actions in several countries in 2010, but the Food and Drug Administration eliminated access restrictions in 2013, reflecting new evidence concerning the drug safety. We investigated the effects of safety signals and regulation shifts concerning rosiglitazone on prescribing of antidiabetic drugs (ADs).

Increased risk of adverse drug events secondary to bevacizumab treatment in patients with advanced or metastatic breast cancer: a meta-analysis of randomized controlled trials

Background A 2013 postmarketing study suggested a possible link between saxagliptin use and hospital admission for heart failure. Cardiovascular (CV) effects of sitagliptin, the most commonly prescribed antidiabetic in the same class as saxagliptin, have not been evaluated much in Asian patients with type 2 diabetes. This study sought to ascertain the CV safety of sitagliptin in Korean patients. Methods A retrospective cohort study of 4,860 patients who were classified into the sitagliptin and metformin groups was conducted using electronic patient data retrieved from a major tertiary care medical center in Korea. Primary composite end points included CV death, myocardial infarction, and ischemic stroke. Secondary composite end points included the aforementioned individual primary outcomes plus hospitalization due to unstable angina, heart failure, or coronary revascularization. A Cox proportional-hazards model was used to compare CV risk associated with drug exposure. Results Following propensity score (PS) matching in a 1:2 ratio, 1,620 patients in the sitagliptin group and 3,240 patients in the metformin group were identified for cohort entry. The PS-matched hazard ratio (HR) and 95% confidence interval (CI) for sitagliptin relative to metformin were, respectively, 0.831 and 0.536–1.289 (P=0.408) for primary end point and 1.140 and 0.958–1.356 (P=0.139) for secondary end point. Heart failure hospitalization rates did not differ significantly between the two groups, with the PS-matched HR of 0.762 and 95% CI of 0.389–1.495 (P=0.430). When only those patients at high risk of ischemic heart disease were included for analysis, no excess CV risk was observed with sitagliptin compared with metformin. Overall, there were no substantial between-group differences in rates of adverse events, such as hypoglycemia and incident pancreatic disease. Conclusion Sitagliptin was not associated with elevated risk of CV complications including myocardial infarction, ischemic stroke, heart failure, and coronary revascularization, compared to metformin therapy among Korean patients with type 2 diabetes.

Durability of initial antidiabetic monotherapy and subsequent treatment adjustment patterns among newly treated type 2 diabetes patients

Background Several clinical trials have shown an increased risk of hypertension with bevacizumab when added to chemotherapy in different types of malignancy; however, the risks of other significant adverse events besides hypertension, specifically in breast cancer, have not been completely elucidated. This study was conducted with the aim, primarily, to assess the overall incidence and risk of common toxicities associated with bevacizumab in patients with advanced or metastatic breast cancer and, secondarily, to descriptively review study results concerning a potential correlation between bevacizumab-induced hypertension and its efficacy for breast cancer treatment. Methods We carried out a meta-analysis of relevant randomized controlled trials (RCTs) identified from a database search (Cochrane Library and PubMed) and, additionally, by reviewing previous reviews and meta-analyses. Overall incidence rates, odds ratios (ORs), and 95% confidence intervals (CIs) were assessed with the random- or fixed-effect models, depending on the level of heterogeneity across the included trials. The primary clinical outcomes were high-grade adverse events commonly reported with bevacizumab therapy. Results We included 6,260 patients with advanced-stage breast cancer from 12 RCTs in the meta-analysis. Five types of high-grade (Grade 3 or 4) adverse drug events were identified as being correlated with bevacizumab treatment versus alternative treatment with statistical significance: hypertension (OR 5.67, 95% CI 3.02–10.65), proteinuria (OR 10.09, 95% CI 4.79–21.27), bleeding (OR 3.45, 95% CI 2.25–5.30), cardiac toxicity (OR 2.15, 95% CI 1.29–3.59), and neutropenic fever (OR 1.51, 95% CI 1.15–2.00). The prognostic value of bevacizumab-induced hypertension for its antitumor efficacy among patients with breast cancer remains controversial, with mixed results presented in the five retrospective studies that were identified from our additional literature search. Conclusion The addition of bevacizumab to anticancer therapy was associated with a significant increase in the risk of high-grade adverse events, including hypertension, proteinuria, bleeding, cardiac toxicity, and neutropenic fever among patients with advanced-stage breast cancer. Although several retrospective studies suggested a predictive importance of hypertension secondary to bevacizumab therapy, the role of elevated blood pressure as a prognostic biomarker for its antitumor efficacy remains controversial, and further prospective trials are required to confirm such a correlation.

Effect of Cilostazol on Incident Dementia in Elderly Men and Women with Ischemic Heart Disease

Background As newly available antidiabetic drugs (ADs) are used more commonly as initial hypoglycemic choice for early stage diabetes patients, there is an urgent need to investigate how these agents may differ in treatment durability relative to metformin. This study aimed to investigate the incidence and risk of treatment adjustment among newly treated type 2 diabetes mellitus (T2DM) patients receiving an oral AD as initial monotherapy. Methods T2DM patients registered in the National Health Insurance Program who were newly prescribed an oral AD were identified. Time to treatment addition or switch to alternative antidiabetic therapy was determined using the Kaplan–Meier survival analysis. Cox proportional hazards regression was performed to estimate the hazard ratio (HR) after adjusting for potential confounding factors. Results The median time to treatment adjustment was shorter for sulfonylureas (SUs), dipeptidyl peptidase-4 (DPP-4) inhibitors, alphaglucosidase (AG) inhibitors, and thiazolidinediones (TZDs) compared to that for metformin. Initiation of therapy with SUs or DPP-4 inhibitors was associated with a significantly higher risk of both treatment addition and switching than with metformin (HR 1.49 versus 1.47 for overall treatment adjustment, respectively). In contrast, among incident users of AG inhibitors or TZDs, only the hazard of switch was substantially increased compared to metformin starters (6.19, 95% confidence interval [CI] 5.77–6.64 and 7.31, 95% CI 6.35–8.42, respectively). When addition and switch events were collectively assessed, the risk of treatment adjustment was significantly elevated in all non-metformin cohorts. Conclusion Our results demonstrated that the durability of metformin as an initial monotherapy was superior to that of other ADs, including newer classes of antidiabetics, and appeared to be more effective in delaying treatment adjustment in real-world clinical practice.