• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.276-283
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• 2017

Objective: Dyslipidemia is recognized as a prominent risk factor for cardiovascular and cerebrovascular diseases but it is manageable through therapeutic and lifestyle intervention. Interpreting the latest guidelines is essential for an application of recommendation from guidelines into clinical practice. Therefore, this study aimed to compare the most recent guidelines on dyslipidemia treatment recommendations in Korea and USA. Methods: This study analyzed and compared 2015 Korean guidelines for the management of dyslipidemia, 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline and 2016 supportive guidelines from ACC. Results: A comparison was made focused on the following: target patients based on cardiovascular risk assessment, target goal, and treatment strategies including statin and non-statin therapies. Four target patient groups by risk were suggested in 2015 Korean guideline and cardiovascular risk factors were also considered for initiation of lipid lowering therapy. Titrated statin regimen was recommended by Korean guideline to reach LDL cholesterol and non-HDL cholesterol target level. In 2013 ACC/AHA guideline, four statin benefit group was introduced considering ASCVD risk and high intensity statin or intermediate intensity statin use were recommended without dose titration. 2016 update was to support non-statin therapy based on updated evidence and new consideration of ezetimibe, PCSK9-inhibitor and bile acid sequestrant was brought up. Conclusion: Guidelines are continuously updating as new and important clinical data are constantly released along with the advent of newly approved drugs for lipid disorder. This article provides resources that facilitates uptake of these recommendations into clinical practice.

• The Journal of Internal Korean Medicine
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• v.38 no.3
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• pp.327-335
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• 2017

Objective: The goal of this preclinical study was to compare the dyslipidemic effect of pravastatin with that of herbal medicine in rats. Methods: In total, 40 rats were divided into 4 groups: Normal (10 rats), Control (10 rats), Statin alone (10 rats), and the MO-PM-S group (10 rats), which was given the powder of the cortex of Magnolia officinalis Rehd. et Wils., the root of Polygonum multiflorum Thunb, and pravastatin. The Control group, the Statin alone group, and the MO-PM-S group were all given a high-fat (45%) diet that made them obese. After 2 weeks of drug administration, the dyslipidemic effect of pravastatin was compared with that of herbal medicine in rats by analyzing the lipid profiles, measuring the body weights, and taking biopsies (liver, aorta). Results: The herbal medicine and the statin complex group got a much lower TG level and a slightly higher HDL-cholesterol level than the other groups. However, it got a higher total cholesterol and LDL-cholesterol level than the other groups. In biopsies, 30% of the Statin alone group and 10% of the MO-PM-S group showed mild histopathologic findings in the liver. Conclusion: The cortex of the Magnolia officinalis Rehd. et Wils. and the root of Polygonum multiflorum Thunb have dyslipidemic effects from the perspective of a TG level and HDL-cholesterol. However, the herbal mixture has a raising effect on both the LDL-cholesterol and the total cholesterol levels. Therefore, we cannot conclude that the herbal mixture helps to prevent dyslipidemia. In liver biopsies, the group administered with both the herbal mixture and the statin showed less histopathologic findings than the group administered with statin alone. This means that the herbal mixture helps to prevent fatty degeneration of the liver.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.293-299
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• 2018

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) effectively reduce serum levels of low-density lipoprotein (LDL) and total cholesterol. High-intensity statins are recommended for all patients aged ${\leq}75$ with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus aged 40-75 with ${\geq}7.5%$ estimated 10-year ASCVD risk and LDL-C ${\geq}190mg/dL$. High-intensity statins associated with more frequent adverse events (AEs) compared to moderate- to low-intensity statins. The aim of this study was to compare AEs between high-intensity and moderate- to low-intensity statin group using the Korea Adverse Event Reporting System (KAERS) database. Methods: Adults (${\geq}18years$) with statin-associated AEs from July 2009-June 2014 were included. Only AEs classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Center criteria were analyzed. Results: In total, 247 AEs from 196 patients [high-intensity statin group (HG), n = 25 (13%); moderate- to low-intensity statin group (MLG), n = 171 (87%)] were included. Mean age was higher in HG compared with MLG ($67{\pm}14$ vs $62{\pm}12$). The HG showed a significant higher frequency of liver/biliary system disorders (37% vs 14%, p = 0.001). Hepatic function abnormal was reported more frequently in HG compared to MLG (26% vs 9%, p = 0.006). Conclusion: According to KAERS data, liver/biliary system disorders were more frequently reported in HG compared to MLG.

• Korean Journal of Clinical Pharmacy
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• v.31 no.4
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• pp.278-284
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• 2021

Background: Osteoporosis is a disease that affects the quality of life and imposes a high socioeconomic burden. Studies have reported that statins, a HMG CoA reductase inhibitor, have a positive or negative effect on osteoporosis. The purpose of this study was to analyze the correlation between statins and osteoporosis risk. Methods: We used the total patient sample data of the Health Insurance Review and Assessment Service (HIRA-NPS-2018). We analyzed the prevalence of osteoporosis in adult patients of Korea who were diagnosed with dyslipidemia and were prescribed statins at the same time. The odds ratio (OR) according to the intensity and type of statin was used to confirming the prevalence. Results: Among the 1,138,899 patients included in the study, 143,895 patients used statins and 27,524 patients (19.13%) were diagnosed with osteoporosis in the statin group. The OR value of statin group was 0.96 (95% CI 0.94-0.98), confirming that the prevalence of osteoporosis decreased, and a significant decrease was seen in all statin intensity. Some of the moderate-intensity statins rather increased the prevalence of osteoporosis, but atorvastatin and rosuvastatin obtained positive results at both medium- and high-intensity doses, and lovastatin, a low-intensity statin, showed the greatest reduction in the prevalence of osteoporosis. Conclusion: We found that the prevalence of osteoporosis was reduced in the statin group, and there was a constant correlation regardless of gender or age. However, a large, prospective, double-blind and randomized study is needed for a long period of time to demonstrate the effectiveness of statins.

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.105-112
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• 2017

Background: Generic medications are approved on the basis of bioequivalence with brand medications in healthy volunteers rather than the target population, there remains a substantial uncertainty regarding their clinical effectiveness and safety. The object of this paper is to compare the clinical equivalence of generic statin drugs in patients. Methods: Literature published before September 2016, which is indexed in PubMed, EMBASE, RISS, comparing generic to brand products in statins. Outcomes included blood lipid level, proportion of days covered (adherence), hospitalization and mortality. Results: 511 citations were screened, of which 11 studies met eligibility criteria (6 randomized clinical trials, 5 observational studies). Generic atorvastatin was clinical equivalent with brand drugs in blood lipid level (3 RCTs) and generic simvastatin was also clinical equivalent with brand drugs (2 RCTs). 2 of 3 studies reported no significant difference in proportion of days covered except 1 study which reported generic statin significantly enhance proportion of days covered (p<0.001). Hospitalization was no significant difference in all studies (p>0.05). 1 study reported that all cause of mortality was significantly low in generic drugs (p<0.0001). Conclusion: Published data on comparing clinical efficacy of generic and brand statins were insufficient in both quantity and quality. This systematic review suggests that additional studies on clinical equivalence and safety of generic medications in patients would be needed.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.171-177
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• 2016

Statins, HMG-CoA reductase inhibitors, are known to cause serious muscle injuries (e.g. myopathy, myositis and rhabdomyolysis), and these adverse effects can be rescued by co-administration of coenzyme $Q_{10}$ ($CoQ_{10}$) with statins. The goal of the current research is to assess the efficacy of combined treatment of $CoQ_{10}$ with Atorvastatin for hyperlipidemia induced by high-fat diet in SD rats. 4-week-old Sprague-Dawley male rats were fed normal diet or high-fat diet for 6 weeks. Then, rats were treated with either Statin or Statin with various dosages of $CoQ_{10}$ (30, 90 or 270 mg/kg/day, p.o.) for another 6 weeks. Compared to Statin only treatment, $CoQ_{10}$ supplementation significantly reduced creatine kinase and aspartate aminotransferase levels in serum which are markers for myopathy. Moreover, $CoQ_{10}$ supplementation with Statin further reduced total fat, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol. In contrast, the levels of high-density lipoprotein-cholesterol and $CoQ_{10}$ were increased in the $CoQ_{10}$ co-treated group. These results indicate that $CoQ_{10}$ treatment not only reduces the side effects of Statin, but also has an anti-obesity effect. Therefore an intake of supplementary $CoQ_{10}$ is helpful for solving problem of obese metabolism, so the multiple prescription of $CoQ_{10}$ makes us think a possibility that can be solved in being contiguous to the obesity problem, a sort of disease of the obese metabolism.

• Journal of Lipid and Atherosclerosis
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• v.7 no.2
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• pp.77-87
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• 2018

Lowering serum low-density lipoprotein cholesterol (LDL-C) is the mainstay for reduction of risk of cardiovascular disease (CVD), the second most common cause of death in Korea. The 2015 Korean guidelines for management of dyslipidemia strongly recommend the use of statins in patients at risk of CVD. Statin therapy, which is the gold standard for CVD, reduces LDL-C level by 40% to 60% and is generally well tolerated. However, many patients are intolerant to statins and discontinue therapy or become nonadherent to therapy because of actual/perceived side effects. The most common of these side effects is the statin-associated muscle symptom (SAMS). Discontinuation and repetitive re-challenge with statins can help identify SAMS. If serum creatinine kinase level is more than 10 times the upper limit of normal, statin therapy must be stopped immediately, and the physician should identify possible causes including rhabdomyolysis and treat appropriately. In other patients, it might help to switch to a less potent statin or to use statins at intermittent non-daily dosing. To achieve target LDL-C level, non-statin lipid-lowering therapies such as dietary modifications, ezetimibe, and bile acid sequestrants may be added. Several new drugs have recently been approved for lowering LDL-C level. Alirocumab and evolocumab are monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, and both drugs cause large reductions in LDL-C, similar to statins. Lomitapide and mipomersen are orphan drugs used as adjuncts to other lipid-lowering therapies in patients with homozygous familial hypercholesterolemia.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.320-332
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• 2018

Background: This study was performed to clarify the effect of SLCO1B1 T521C on statin-induced myotoxicity. Methods: The PubMed, Embase, Ovid, and Cochrane Library databases were searched for all published studies between database inception and April 2018. Using Review Manager 5, the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were determined to assess the effect of SLCO1B1 T521C on statin-induced myotoxicity by using different genetic models. Results: Eleven observational studies and one randomized controlled trial were included in the meta-analysis. The pooled analysis showed that the incidence of statin-induced myotoxicity was significantly associated with the SLCO1B1 521C variant allele. Among patients using statins, the incidence of myotoxicity was higher in those carrying the 521TC or 521CC variant than in those carrying the 521TT variant in the dominant model (TC + CC vs TT, OR: 1.57; 95% CI: 1.20, 2.05; p = 0.001). The 521TC genotype was associated with a higher risk of myotoxicity than the 521TT genotype (OR: 1.42; 95% CI: 1.09, 1.86; p = 0.009). Furthermore, the incidence of myotoxicity was higher in 521CC carriers than in 521TC carriers (OR: 1.40; 95% CI: 1.06, 1.83; p = 0.02) and noticeably higher in 521CC carriers than in 521TT carriers (OR: 2.26; 95% CI: 1.23, 4.17; p = 0.009). Conclusion: The identification of individuals with the SLCO1B1 521C variant allele prior to the initiation of statin therapy might be useful to predict the risk of toxicity development, determine the individual dose, and prevent myotoxicity.

• Korean Circulation Journal
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• v.54 no.9
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• pp.534-544
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• 2024

Background and Objectives: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. Methods: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. Results: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio [HR], 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. Conclusions: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

• Korean Circulation Journal
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• v.52 no.12
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• pp.890-900
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• 2022

Background and Objectives: Some individuals exhibit discrepancies between risk classifications assessed using clinical factors and those obtained by vascular imaging. We aimed to evaluate whether statins provide clinical outcome benefits in patients classified as having low to moderate cardiovascular risk but with carotid plaque. Methods: This was a retrospective propensity score matching study. A total of 12,158 consecutive patients undergoing carotid ultrasound between January 2012 to February 2020 were screened. Individuals with low to moderate cardiovascular risk who were not currently recommended for statin therapy but had carotid plaques were included. Among 1,611 enrolled individuals, 806 (statin group: 403, control group: 403) were analyzed. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs: cardiovascular death, myocardial infarction, coronary revascularization, and ischemic stroke or transient ischemic attack) and all-cause mortality. Results: During the median follow-up of 6.0 years, the incidence of MACCEs did not differ between the groups (6.1 and 5.7/1,000 person-years in the control and statin groups, respectively; adjusted hazard ratio [HR], 0.95; p=0.90). The incidence of all-cause mortality did not differ (3.9 and 3.9/1,000 person-years, respectively; adjusted HR, 1.02; p=0.97). Kaplan-Meier curves revealed similar rates of MACCEs (log-rank p=0.72) and all-cause mortality (log-rank p=0.99) in the 2 groups. Age and smoking were independent predictors of MACCEs. Subgroups exhibited no differences in clinical outcomes with statin use. Conclusions: Benefit of statin therapy was likely to be limited in low to moderate risk patients with carotid plaques. These results could guide physicians in clinical decision-making regarding cardiovascular prevention.