Atorvastatin is one of the most widely prescribed medications for dyslipidemia treatment. In Korea, post combined therapy with ezetimibe, a 73-year-old woman was reported by a community pharmacy to have experienced visual field defect, which recovered after drug discontinuation. She had never experienced this symptom before, and several studies have reported an association between use of statins and visual disorders such as blurred vision, diplopia, and cataract. Blockage of cholesterol accumulation, oxidative stress, or myopathy is expected to be a cause of this symptom. Naranjo scale, Korean causality assessment algorithm (Ver.2), and World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria were the three tools used to determine causality between the visual disorder and atorvastatin. The results represent ‘probable’, ‘certain’, and ‘probable/likely’ causality, respectively. Our results, in combination with a review of literature, indicate that ocular adverse effects are highly likely related to atorvastatin.
Aged ; Atorvastatin Calcium ; Cataract ; Cholesterol ; Diplopia ; Drug-Related Side Effects and Adverse Reactions ; Dyslipidemias ; Ezetimibe ; Female ; Global Health ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Muscular Diseases ; Oxidative Stress ; Pharmacies ; Vision Disorders ; Visual Fields

BACKGROUND AND OBJECTIVES: Non-statin therapy plus lower intensity statin might be an alternative in patients with coronary artery disease (CAD). A recent data suggested an anti-inflammatory therapy can reduce recurrent cardiovascular events and pioglitazone is also an intriguing inflammatory-modulating agent. However, limited data exist on whether pioglitazone on top of statins further attenuates plaque inflammation. METHODS: Statin-naïve patients with stable CAD and carotid plaques of ≥3 mm were randomly prescribed moderate dose atorvastatin (20 mg/day), or moderate dose atorvastatin plus pioglitazone (30 mg/day) for 3 months. The primary endpoint was the change in the arterial inflammation of the carotid artery measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during 3 months. RESULTS: Of the 41 randomized patients, 33 underwent an evaluation by fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT; 17 atorvastatin plus pioglitazone and 16 atorvastatin patients). The addition of pioglitazone significantly improved the insulin sensitivity and increased the high-density lipoprotein cholesterol after 3 months. Although a reduction in the (FDG) uptake by pioglitazone on top of atorvastatin in carotid arteries with plaque showed marginally statistical significance in the entire patient group (atorvastatin plus pioglitazone; −0.10±0.07 and atorvastatin −0.06±0.04, p=0.058), pioglitazone showed a further reduction of the fluorodeoxyglucose (FDG) uptake among patients who had a baseline FDG uptake above the median (atorvastatin plus pioglitazone; −0.14±0.04 and atorvastatin −0.03±0.03, p < 0.001). CONCLUSIONS: Pioglitazone demonstrated marginally significant anti-inflammatory effects in addition to moderate dose atorvastatin. This may have been due to the lack of power of the study. However, pioglitazone may have an anti-inflammatory effect in those patients with high plaque inflammation (Trial registry at ClinicalTrials.gov, NCT01341730).
Arteritis ; Atherosclerosis ; Atorvastatin Calcium ; Carotid Arteries ; Carotid Stenosis ; Cholesterol ; Coronary Artery Disease ; Electrons ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammation ; Insulin Resistance ; Lipoproteins ; PPAR gamma

BACKGROUND: The proportion of pharmaceutical expenditure out of total health-care expenditure in South Korea is high. In 2016, 25.7% of national health insurance (NHI) spending was for pharmaceuticals. Given the increasing demands for the access to newly introduced medicines and following increase in pharmaceutical spending, the management of NHI pharmaceutical expenditure is becoming more difficult. METHODS: This study analyzed the data claimed to NHI for pharmaceutical reimbursement from 2010 to 2016. RESULTS: The policy implications with respect to the trends and problems in spending by drug groups were elicited. First, the proportion of off-patent drugs spending which were treated to chronic disease was much higher than anti-cancer drug spending. Second, the spending to the newly introduced high-costed medicine increased, however, current price-reduction mechanism was not sufficient to manage their expenditure efficiently. CONCLUSION: Our system seems to need several revisions to improve the efficiency of pharmaceutical expenditure and to cope with high-costed medicines. This study suggested that the prices of off-patent drugs need to be regularly readjusted and the Price-Volume Agreement System should be operated more flexibly as well.
Atorvastatin Calcium ; Chronic Disease ; Health Expenditures ; Imatinib Mesylate ; Korea ; National Health Programs

BACKGROUND/AIMS: To define the effect of statins on interleukin 1β (IL-1β)-induced osteoclastogenesis and elucidate the underlying mechanisms. METHODS: Bone marrow cells were obtained from 5-week-old male ICR (Institute for Cancer Research) mice, and they were cultured to differentiate them into osteoclasts with macrophage colony-stimulating factor and the receptor activator of nuclear factor (NF)-κB ligand in the presence or absence of IL-1β or atorvastatin. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the effects of atorvastatin on osteoclastogenesis were investigated using reverse transcription polymerase chain reaction and immunoblotting for osteoclast specific molecules. RESULTS: Atorvastatin significantly reduced the number of TRAP-positive multinucleated cells as well as the bone resorption area. Atorvastatin also downregulated the expression of the NF of activated T-cell c1 messenger RNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-κB and blocks the activation of the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38; thus, implicating the NF-κB and mitogen-activated protein kinases pathway in this process. CONCLUSIONS: Atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases.
Acid Phosphatase ; Animals ; Atorvastatin Calcium* ; Bone Marrow Cells ; Bone Resorption ; Dentin ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Immunoblotting ; Interleukins ; JNK Mitogen-Activated Protein Kinases ; Joint Diseases ; Macrophage Colony-Stimulating Factor ; Male ; Mice ; Mitogen-Activated Protein Kinases ; Osteoclasts* ; Osteoprotegerin ; Phosphotransferases ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; T-Lymphocytes

Blastocystis is an enteric Straminopile in tropical, subtropical and developing countries. Metronidazole has been a chemotheraputic for blastocystosis. Failures in its regimens were reported and necessitate new studies searching for alternative therapeutic agents. Aim of current study is to investigate potential effects of Atorvastatin (AVA) compared to the conventional chemotherapeutic MTZ in experimentally Blastocystis-infected mice. Anti-Blastocystis efficacy of AVA was evaluated parasitologically, histopathologically and by transmission electron microscopy using MTZ (10 mg/kg) as a control. Therapeutic efficacy of AVA was apparently dose-dependent. Regimens of AVA (20 and 40 mg/kg) proved effective against Blastocystis infections with high reduction in Blastocystis shedding (93.4–97.9%) compared to MTZ (79.3%). The highest reductions (98.1% and 99.4%) were recorded in groups of combination treatments AVA 20–40 mg/kg and MTZ 10 mg/kg. Blastocystis was nearly eradicated by the 20th day post infection. Genotype analysis revealed that genotype I was most susceptible, genotype III was less. Histopathologic and ultrastructural studies revealed apoptotic changes in Blastocystis and significant improvement of intestinal histopathological changes more remarkable in combinational therapy groups. Thus, the present study offers AVA as a potential candidate for Blastocystis therapy combined with MTZ.
Animals ; Atorvastatin Calcium ; Blastocystis ; Blastocystis Infections ; Developing Countries ; Genotype ; Metronidazole ; Mice ; Microscopy, Electron, Transmission

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.
Animals ; Atorvastatin Calcium* ; Brain ; Cardiovascular Diseases ; Cell Death ; Cyclooxygenase 2 ; Hippocampus ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Kainic Acid ; Mice ; Neurons* ; Phosphorylation ; Prevalence ; Seizures

BACKGROUND: There has been evidences of ethnic differences in the low density lipoprotein cholesterol (LDL-C) lowering effect of statin. We aimed to evaluate the efficacy of moderate-intensity statins in the treatment of dyslipidemia among Korean patients with type 2 diabetes mellitus (T2DM). METHODS: We analyzed a retrospective cohort that consisted of Korean patients with T2DM aged 40 to 75 years who had been prescribed any of the moderate-intensity statins (atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, or pravastatin 40 mg). Among them, only patients with baseline lipid profiles before starting statin treatment were selected, and changes in their lipid profiles before and 6 months after statin therapy were analyzed. RESULTS: Following the first 6 months of therapy, the overall LDL-C reduction was −47.4% (interquartile range, −56.6% to −34.1%). In total, 92.1% of the participants achieved an LDL-C level of <100 mg/dL, 38.3% had a 30% to 50% reduction in their LDL-C levels, and 42.3% had a reduction in their LDL-C levels greater than 50%. The response rates of each drug for achieving a LDL-C level <100 mg/dL were 81.7%, 93.1%, 95.0%, 95.0%, 96.5%, and 91.7% for treatment with atorvastatin doses of 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, and pravastatin 40 mg, respectively. CONCLUSION: In conclusion, the use of moderate-intensity statins reduced LDL-C levels less than 100 mg/dL in most of the Korean patients studied with T2DM. The efficacies of those statins were higher than expected in about 42% of Korean patients with T2DM.
Atorvastatin Calcium ; Cholesterol, LDL ; Cohort Studies ; Diabetes Mellitus, Type 2* ; Dyslipidemias* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Pravastatin ; Retrospective Studies ; Rosuvastatin Calcium

STUDY DESIGN: Clinical trial study. PURPOSE: The aim of this study was to evaluate the effect of atorvastatin on sensory and motor function in patients with acute spinal cord injury. OVERVIEW OF LITERATURE: The prevalence and incidence of traumatic spinal cord injury are increasing. Statins are well established for use in hypercholesterolemia as well as during anti-inflammatory events. METHODS: This clinical trial study included 60 patients with acute spinal cord injury. These were randomly divided into two groups: the case group which received atorvastatin and also underwent surgical therapy and the control group which only underwent surgical therapy. RESULTS: The severity of spinal cord lesions was evaluated based on the Frankel grade at three periods; this showed no significant difference between the two groups. Comparisons of the levels of pain between the groups based on a Visual Analog Scale system showed no significant difference at the three periods. CONCLUSIONS: We observed no improvement at the 3- and 6-month follow-up in patients who were administered atorvastatin. However, a comparison of the two groups based on pain severity demonstrated a significant difference, suggesting that atorvastatin had a positive effect on patients with spinal cord injury.
Atorvastatin Calcium* ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Incidence ; Prevalence ; Spinal Cord Injuries* ; Spinal Cord* ; Visual Analog Scale

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.
Atorvastatin Calcium ; Drugs, Generic ; Health Services Needs and Demand ; Healthy Volunteers ; Hospitalization ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Mortality ; Simvastatin ; Therapeutic Equivalency ; Treatment Outcome ; Uncertainty

BACKGROUND: Imatinib mesylate is an inhibitor of the tyrosine kinase Bcr–Abl and a first-line treatment for Philadelphia chromosome-positive chronic myeloid leukaemia (CML). Dermatological side effects include superficial oedema, pustular eruption, lichenoid reactions, erythroderma, and skin rash. Depigmentation of the skin and/or mucosa is uncommon, and hyperpigmentation is rare. CASE PRESENTATION: We present the case of a 63-year-old Caucasian male with widespread hyperpigmentation of the hard palate associated with a 9-year history of imatinib therapy to treat CML. He did not complain of any symptoms. Clinical examination did not reveal any abnormal pigmentation of the skin or other region of the oral mucosa. He did not smoke cigarettes or drink alcohol. His medication regimen was a proton pump inhibitor, a beta-blocker, cardioaspirin, atorvastatin, and imatinib 400 mg/day. Histopathologically, melanin and haemosiderin deposits were evident in the lamina propria. The lesion persisted, with no clinical change, through several follow-ups. We reviewed the literature to explore the possible relationship between oral hyperpigmentation and long-term imatinib mesylate treatment. CONCLUSIONS: We diagnosed oral pigmentation associated with imatinib intake based on the medical history and clinical features of the pigmented macules. Oral pigmentation may have a variety of causes, and differential diagnosis requires nodal analysis. Clinicians should be aware of possible oral mucosal hyperpigmentation in patients taking imatinib mesylate. Such pigmentation is benign and no treatment is needed, but surveillance is advisable.
Atorvastatin Calcium ; Dermatitis, Exfoliative ; Diagnosis, Differential ; Exanthema ; Follow-Up Studies ; Humans ; Hyperpigmentation* ; Imatinib Mesylate* ; Lichenoid Eruptions ; Male ; Melanins ; Middle Aged ; Mouth Mucosa ; Mucous Membrane* ; Palate, Hard* ; Pigmentation ; Protein-Tyrosine Kinases ; Proton Pumps ; Skin ; Smoke ; Tobacco Products