Atorvastatin Group Research Articles

Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents?

Introduction and objectivesTo compare the pharmacodynamics of the CNIC polypill (atorvastatin 40mg/ramipril 10mg/aspirin 100mg) in terms of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP), with the corresponding reference products (atorvastatin and ramipril). MethodsThis was a multicenter, randomized, open-label, and parallel 3-arm study comparing the effect of the CNIC polypill vs ramipril 10mg and atorvastatin 40mg on SBP and LDL-C. The coprimary endpoints were differences in the adjusted mean 24-hour SBP (using ambulatory BP measurement) and LDL-C during the study period estimated using an ANCOVA model. ResultsOf the 241 patients included in the per protocol population, 84 received the CNIC polypill (group A), 84 atorvastatin (group B), and 73 ramipril (group C). SBP decreased from 139.3±12.5 to 133.2±12.9mmHg in group A and from 138.1±11.9 to 134.0±12.8mmHg in group C (baseline adjusted mean difference for the decrease in SBP was 1.77mmHg (90%CI, −0.5 to 4.0) in favor of group A, without reaching statistical significance. LDL-C was reduced by 33.9±21.6 and 29.2±25.8mg/dL in groups A and B, respectively (baseline adjusted mean difference for the decrease in LDL-C was 7.0% (90%CI, 1.5–12.4), a significantly greater decrease with the polypill). The 3 treatments were well tolerated. ConclusionsThe results of this study rule out a negative effect on blood pressure of the interaction between the components of the CNIC polypill. The reduction in LDL-C was greater in the CNIC polypill group, suggesting a synergistic effect of the components.

Effect of resveratrol combined with atorvastatin on re-endothelialization after drug-eluting stents implantation and the underlying mechanism

AimsTo explore whether the combination of atorvastatins and resveratrol is superior to each individual drug alone regarding re-endothelialization after drug-eluting stents (DESs) implantation. Materials and methodsNinety-four rabbits were randomized into control, atorvastatin, resveratrol, and combined medication groups. Abdominal aorta injury was induced via ballooning, followed by DES implantation. Neointimal formation and re-endothelialization after stent implantation were assessed via optical coherence tomography and scanning electron microscopy. The effects of resveratrol and atorvastatin on bone marrow-derived mesenchymal derived stem cells (BMSCs) were assessed. Key findingsCompared with the findings in the resveratrol and atorvastatin groups, the neointimal area and mean neointimal thickness were greater in the combined medication group, which also exhibited improved re-endothelialization. Compared with the effects of monotherapy, combined treatment further protected BMSCs against rapamycin-induced apoptosis and improved cell migration. Combined medication significantly upregulated Akt, p-Akt, eNOS, p-eNOS, and CXCR4 expression in BMSCs compared with the effects of monotherapy, and these effects were abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. SignificanceThe combination of atorvastatin and resveratrol has the potential of accelerating re-endothelialization after stent implantation, reducing the risk of thrombosis and improving the safety of DESs.

Outcome of pitavastatin versus atorvastatin therapy in patients with hypercholesterolemia at high risk for atherosclerotic cardiovascular disease.

There has been no report about outcome of pitavastatin versus atorvastatin therapy in high-risk patients with hypercholesterolemia. Hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases (n=664, age=65, male=54%, diabetes=76%, primary prevention=74%) were randomized to receive pitavastatin 2mg/day (n=332) or atorvastatin 10mg/day (n=332). Follow-up period was 240weeks. The primary end point was a composite of cardiovascular death, sudden death of unknown origin, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, or heart failure requiring hospitalization. The secondary end point was a composite of the primary end point plus clinically indicated coronary revascularization for stable angina. The mean low-density lipoprotein cholesterol (LDL-C) level at baseline was 149mg/dL. The mean LDL-C levels at 1year were 95mg/dL in the pitavastatin group and 94mg/dL in the atorvastatin group. There were no differences in LDL-C levels between both groups, however, pitavastatin significantly reduced the risk of the primary end point, compared to atorvastatin (pitavastatin=2.9% and atorvastatin=8.1%, HR, 0.366; 95% CI 0.170-0.787; P=0.01 by multivariate Cox regression) as well as the risk of the secondary end point (pitavastatin=4.5% and atorvastatin=12.9%, HR=0.350; 95%CI=0.189-0.645, P=0.001). The results for the primary and secondary end points were consistent across several prespecified subgroups. There were no differences in incidence of adverse events between the statins. Pitavastatin therapy compared with atorvastatin more may prevent cardiovascular events in hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases despite similar effects on LDL-C levels.

Effects of atorvastatin on serum lipids, cardiomyocyte apoptosis and related genes in rats

ObjectiveTo investigate effects of different doses of atorvastatin on serum lipids, cardiomyocyte apoptosis and related genes in rats with myocardial infarction. Methods60 SD rats were randomized into control group (n = 12) and modeling group (n = 48). The models were established by ligation of left anterior descending (LAD) in rats. 5wk later, the rates after successful modeling were divided into modeling group (n = 12) and treatment group (n = 36), and treatment group was equally divided into low dose group (20 mg/kg atorvastatin daily), medium does group (40 mg/kg atorvastatin daily) and high does group (80 mg/kg atorvastatin daily). After administration, the ratio of heart weight (HW) to body weight (BW) was calculated (HW/BW). Contents of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and moderate – high density lipoprotein cholesterol (HDL-C) in serum of rats were measured. Apoptosis index of rat cardiomyocytes was detected with TUNEL method. Expression levels of Caspase-3, Bax, and Bcl-2 proteins in each group were detected by Western blot. ResultsCompared with control group, heart surface of modeling group was rough, and weight of model group was significantly higher than that of control group, low, medium and high dose groups after 9 weeks of modeling (P < 0.05). TC, TG, and LDL-C in modeling group were significantly higher than those in control group (P < 0.05), HDL-C was significantly lower than those in control group (P < 0.05). Changes in blood lipid-related indicators could be improved after administration, and the higher the dose, the better the improvement effect. Apoptosis index of cardiomyocytes in modeling group, the low, medium and high dose group was significantly higher than that in control group (P < 0.05), but apoptosis of cardiomyocytes was significantly reduced in atorvastatin group at different doses. The higher the dose, the more obvious the reduction effect. The expressions of Caspase-3, Bax, and Bcl-2 proteins in modeling group, low, medium and high dose groups were significantly higher than those in control group (P < 0.05), but administration group significantly reduced apoptosis of myocardial cells, and the higher the dose, the more significant the reduction effect. ConclusionAtorvastatin can reduce TC, TG and LDL-C levels and increase HDL-C level in blood lipids, inhibit expressions of Caspase-3 and Bax and raise expression of Bcl-2 protein so as to inhibit cardiac hypertrophy, reduce cardiomyocyte apoptosis, restore myocardial function and improve myocardial infarction symptoms.

Impact of genetic variants of selected cytochrome P450 isoenzymes on pharmacokinetics and pharmacodynamics of clopidogrel in patients co-treated with atorvastatin or rosuvastatin.

Impaired antiplatelet effect of clopidogrel (CLP) can result from drug-drug interactions and genetic polymorphisms of drug-metabolizing enzymes. The aim of the study was to evaluate the effect of genetic polymorphisms of ABCB1 and the selected cytochrome P450 isoenzymes on the pharmacodynamics and pharmacokinetics of CLP and its metabolites in patients co-treated with atorvastatin or rosuvastatin. The study involved 50 patients after coronary angiography/angioplasty treated with CLP and atorvastatin (n= 25) or rosuvastatin (n= 25) for at least 6months. Plasma concentrations of CLP, diastereoisomers of thiol metabolite (inactive H3 and active H4), and inactive CLP carboxylic acid metabolite were measured by UPLC-MS/MS method. Identification of the CYP2C19*2, CYP2C19*17, CYP3A4*1G, CYP1A2*1F, and ABCB1 C3435T genetic polymorphisms was performed by PCR-RFLP, while platelet reactivity units (PRU) were tested using the VerifyNow P2Y12 assay. There were significant differences in the pharmacokinetic parameters of the H4 active metabolite of CLP in the atorvastatin and rosuvastatin group divided according to their CYP2C19 genotype. There were no significant associations between CYP3A4, CYP1A2, and ABCB1 genotypes and pharmacokinetic parameters in either statin groups. In the multivariate analysis, CYP2C19*2 genotype and non-genetic factors including BMI, age, and diabetes significantly affected platelet reactivity in the studied groups of patients (P< 0.01). In the atorvastatin group, CYP2C19*2, CYP3A4*1G, and ABCB1 C3435T TT genotypes were independent determinants of PRU values (P< 0.01). The CYP2C19*2 allele is the primary determinant of the exposition to the H4 active metabolite of clopidogrel and platelet reactivity in patients co-treated with atorvastatin or rosuvastatin.

Comparison of atorvastatin and rosuvastatin on preventing contrast-induced-nephropathy in patients undergoing primary percutaneous coronary intervention: A multi-centric randomized triple-blind clinical trial

Background: Patients with Contrast-Induced-Nephropathy (CIN) are at a greater risk of in-hospital complications, longer hospitalization, and long-term mortality in comparison with those without CIN. Despite many studies on the helpful effects of statins in preventing contrast-nephropathy, there is not enough evidence comparing different statins in inhibiting CIN. So, we planned this study to compare the efficacy of rosuvastatin and atorvastatin in prevention of contrast-induced nephropathy. Methods: This was a randomized clinical trial. The efficacy of two known statins, atorvastatin and rosuvastatin were compared in prevention of CIN in patients with ST-Elevation Myocardial Infarction (STEMI) who underwent Primary Percutaneous Intervention (PPCI) between May 2015 and April 2016 in Qaem and Imam Reza hospital, Mashhad, Iran. Subjects were divided randomly to 80-mg atorvastatin or 40-mg rosuvastatin group before PPCI. Participants’ characteristics including echocardiographic, laboratory and demographic data were recorded and incidence of CIN was assessed. Results: Two hundred cases with STEMI undergoing PPCI were recruited in the study and randomized to 80-mg atorvastatin (n = 98) or 40-mg rosuvastatin (n = 102) group before PPCI. The incidence of CIN was 5.67% (n = 13) in all participants; 6.3% (n = 7) in the rosuvastatin group and 5.1% (n = 6) in the atorvastatin group. There was a significant difference between creatinine and Glomerular Filtration Rate (GFR) after 48 hours of PPCI. Creatinine was lower and GFR was higher in the rosuvastatin group (P = 0.029, P = 0.005). Conclusion: There was a little trend for prevention of CIN in patients after PPCI in rosuvastatin group compared to atorvastatin group, in full dose. However, this preference was not clinically relevant.

Protective effects of Naoxintong capsule alone and in combination with ticagrelor and atorvastatin in rats with Qi deficiency and blood stasis syndrome

Context Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics. Objective This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO). Materials and methods Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1β, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured. Results NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49). Conclusions The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.

The Role of Wnt/beta-Catenin Signal Pathway in the Pathogenesis of Nonalcoholic Fatty Liver Disease and the Effect of Atorvastatin Intervention

The purpose of this study was to analyze the pathogenesis of nonalcoholic fatty liver disease in rats and study the efficacy of atorvastatin intervention. One hundred Sprague Dawley rats were selected as test system. These rats were randomly divided into 5 groups, the control group, the nonalcoholic fatty liver disease group, high-dose atorvastatin group, medium-dose atorvastatin group and low-dose atorvastatin group, each containing 20 animals. An equal dose of sodium carboxymethylcellulose was applied to the model group and the control group; while atorvastatin perfusion was given to the other 3 groups. The levels of serum aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein and malondialdehyde were compared among the groups. The serum levels of aspartate aminotransferase, alanine aminotransferase, triacylglycerol and total cholesterol of the high-fat diet model group were significantly higher; moreover, the expression levels of MMP2, MMP9, Wnt1, Wnt4, host-catenin were significantly elevated. Treatment with atorvastatin could effectively ameliorate this abnormal condition but at high doses. Atorvastatin appears to inhibit the Wnt/β-catenin signal pathway and achieve good curative effect against nonalcoholic fatty liver disease.

Mechanism of Atorvastatin in Improving Cardiac Function in a Rat Model of Myocardial Infarction

In order to explore the mechanism of atorvastatin on cardiac function after myocardial infarction in rats, 40 male Sprague Dawley rats were divided into 4 groups. There were 8 rats in blank group, 8 in control group, 8 in sham operated group and 16 in atorvastatin group. Atorvastatin group is divided into high dose group (30 mg/kg/d) and low dose group (10 mg/kg/d), 8 rats in each group. A rat model of myocardial infarction was established by ligating the left anterior descending artery. The effect of atorvastatin on cardiac function after myocardial infarction was observed. Cardiac function of rats that included the left ventricular ejection fraction, left ventricular end systolic diameter, left ventricular end diastolic diameter and left ventricular fraction shortening were measured and analysed using ultrasound. Blood lipids of rats in each group including total cholesterol, triglycerides, high density lipoprotein and low-density lipoprotein were measured. After 4 w of treatment rats were sacrificed, myocardial tissue was stained with HE and Masson to observe cardiac fibrosis. Results showed that 4 w after ligation, compared to the control group, the levels of left ventricular end systolic and left ventricular end diastolic diameter was decreased significantly in atorvastatin-treated groups A1 and A2, while left ventricular ejection fraction and left ventricular fraction shortening increased significantly. On 4 w after ligation, total cholesterol and lowdensity lipoprotein cholesterol levels in A1 and A2 groups were significantly lower than those in control group. Compared to the control group, the areas of myocardial infarction and cardiac fibrosis in A1 and A2 groups were significantly reduced. It is concluded that atorvastatin could inhibit apoptosis of myocardial cells, reverse ventricular remodeling and improve cardiac function after myocardial infarction, and these findings are of clinical significance.

A Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney in Albino Rats

Background: therapy hypercholesterolemia used mainly statin group which considered as the main disorder human metabolism and may be led later to suffer from disease future like myocardial infraction. By competitive inhibition 3-hydroxy-3-methylglutaryl-coenzyme reductase (HMGCR), the main function statins to decrease serum levels cholesterol and then limited the severity atherosclerotic cardiovascular disease. Method: This study was conducted on 18 albino rats weighting between (200-300) g. They were separated into three groups each group consist six animals maintained animal house university Karbala/ college pharmacy with free access to food and water ad libitum. As the following: Control group: drenched normal saline for 60 days. Atorvastatin group: drenched 0.6 mg/kg/day atorvastatin, for 60 days. Pitavastatin group: drenched 1mg/kg/day for 60 days. Objective: To determine the toxicity, and safety compared with rats, and the effect high doses on kidney and liver functions. Results: The results showed elevated significantly (p 0.05) concentration ALP and when compared with control group, also the difference is significantly concentration AST group when compared with healthy group ,for the more the deficiency is significant in (ALP and AST) pitavastatin group when compared with group. Also, the elevation the concentration and Creatinin of group is not significantly when compared with healthy group at(p>0.05) and pitavastatin group when compared with healthy group and group while there is significant difference (p<0.05) the concentration urea group when compared between the three groups. Conclusions: The study conclude that the safer than atorvastatin , especially hepatitis patients ,while patients with renal failure disease is more safe. How to Cite this Article Pubmed Style Al-kareem ZA, Kadhim SH, Naser IH. Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Rats. SRP. 2020; 11(10): 1224-1227. doi:10.31838/srp.2020.10.175 Web Style Al-kareem ZA, Kadhim SH, Naser IH. Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Rats. http://www.sysrevpharm.org/?mno=57345 [Access: March 29, 2021]. doi:10.31838/srp.2020.10.175 AMA (American Medical Association) Style Al-kareem ZA, Kadhim SH, Naser IH. Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Rats. SRP. 2020; 11(10): 1224-1227. doi:10.31838/srp.2020.10.175 Vancouver/ICMJE Style Al-kareem ZA, Kadhim SH, Naser IH. Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Rats. SRP. (2020), [cited March 29, 2021]; 11(10): 1224-1227. doi:10.31838/srp.2020.10.175 Harvard Style Al-kareem, Z. A., Kadhim, . S. H. & Naser, . I. H. (2020) Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Rats. SRP, 11 (10), 1224-1227. doi:10.31838/srp.2020.10.175 Turabian Style Al-kareem, Zahraa Abed, Shatha Hussein Kadhim, and Iman Hussein Naser. 2020. Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Reviews Pharmacy, 11 (10), 1224-1227. doi:10.31838/srp.2020.10.175 Chicago Style Al-kareem, Zahraa Abed, Shatha Hussein Kadhim, and Iman Hussein Naser. A Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Rats. Systematic Reviews Pharmacy 11 (2020), 1224-1227. doi:10.31838/srp.2020.10.175 MLA (The Modern Language Association) Style Al-kareem, Zahraa Abed, Shatha Hussein Kadhim, and Iman Hussein Naser. A Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Rats. Systematic Reviews Pharmacy 11.10 (2020), 1224-1227. Print. doi:10.31838/srp.2020.10.175 APA (American Psychological Association) Style Al-kareem, Z. A., Kadhim, . S. H. & Naser, . I. H. (2020) Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney Albino Reviews Pharmacy, 11 (10), 1224-1227. doi:10.31838/srp.2020.10.175

Investigation on the mode of action of the traditional chinese medical prescription-yiqihuoxue formula, an effective extravasation treatment for cerebral vascular microemboli in ApoE-/- mice

Objective: The objective of this study was to investigate the mechanisms underlying anti-embolism and extravasational effects of traditional Chinese medical prescription YiqiHuoxue (YQHX) formula in ApoE-/-mice with cerebral vascular microemboli. Materials and Methods: An ApoE-/-mice model with microemboli was developed by infusing fluorescently labeled heterologous fibrin-rich microparticles into the internal carotid artery of ApoE-/-gene knockout male mice through the common carotid artery. Before microemboli injection, the animals were randomly divided into four groups of 10 animals, treated daily for 6 weeks by intragastric administration: The ApoE-/-control group (physiological saline, 0.2 mL/10 g/d), YQHX group (0.2 ml/10 g/d), clopidogrel group (3 mg/kg/d), and atorvastatin group (3 mg/kg/d); a further group was constituted of normal male C57BL/6J mice (with the same genetic background as ApoE-/-mice; normal control group; no treatment; microemboli injection). The mice in each microemboli group were divided into three subgroups, the 2-h, 24-h, and 72-h subgroups, corresponding to the time after microemboli injection. Two hours (or 24 h or 72 h) after microemboli injection, the changes in aortic intima and brain tissue were analyzed by histopathology, the amounts of fluorescent emboli being measured by fluorescence microscopy image analysis. Comparison points included the microemboli induced loss of aorta functions and pathological changes, atherosclerotic plaque, brain ultrastructure and functions, and embolus extravasation. Results: Loss of aorta functions and adverse pathological changes, atherosclerotic plaque, serious damage in brain ultrastructure and functions, and reduced thrombus elimination were obviously serious in microemboli injected ApoE-/-mice. These symptoms were significantly relieved by the YQHX pretreatment: (i) the ratio of thrombus accumulation was increased with a significant decrease in thrombus extravasation in ApoE-/-mice, while YQHX induced an increased thrombus extravasation; (ii) the degree of aortic intimal thickening and brain tissue structural disorders were significantly increased in ApoE-/-mice, but overtly inhibited in the YQHX group; (iii) YQHX restored cell viability and homeostasis in the brain; (iv) YQHX regulated the expression of pro- and anti-inflammatory cytokines in the aorta; and (v) YQHX reduced cortical nerve nuclei pyknosis, edema, liquefaction, and necrosis induced by brain hypoxia, especially in the 24 h and 72 h groups. Conclusions: These findings indicate that the protective effects of YQHX on the brain against microemboli-induced injury may be attributed to the activation of extravasation mechanisms, which are involved in the cerebrovascular injury pathway and constitutively important in the progression of ischemic stroke.

A comparative study on the anti-inflammatory effect of angiotensin-receptor blockers & statins on rheumatoid arthritis disease activity.

Background & objectives:Rheumatoid artherits (RA) is a refractory disease and the imbalance between pro- and anti-inflammatory cytokines in favor of pro-inflammatory cytokines has been implicated in pathogenesis of RA. In this context, the aim of the present study was to compare the anti-inflammatory and antioxidant effects of candesartan, an angiotensin-receptor blocker, and atorvastatin in RA patients.Methods:In this single-blinded parallel randomized placebo controlled study, the patients recruited between December 2017 and May 2018 were categorized into three groups: group 1 included 15 RA patients who served as control group and received traditional therapy (+ placebo); group 2 included 15 RA patients who received traditional therapy + candesartan (8 mg/day); and group 3 included 15 patients who received traditional therapy + atorvastatin (20 mg/day) for three months. Clinical status in RA patients was evaluated by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI) and morning stiffness before and three months after treatment. All groups were subjected to biochemical analysis of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and malondialdehyde (MDA) before and three months after treatment.Results:Both candesartan and atorvastatin treated groups showed significant decrease in serum levels IL-1β and TNF-α, acute-phase reactants (CRP and ESR), number of swollen joint and patient global assessment. This was also associated with improvement in disease activity and quality of life regarding DAS28 and HAQ-DI as compared to baseline data and the control group. Atorvastatin group showed significant decrease in the serum level of oxidative stress marker (MDA).Interpretation & conclusions:Both candesartan and atorvastatin showed anti-inflammatory effect and immunomodulatory effects leading to improvement in clinical status and disease activity in RA patients. However, atorvastatin was superior to candesartan through its anti-oxidant effect.

Effect of atorvastatin on lipid and cardiovascular events in patients on maintenance hemodialysis

Background: Cardiovascular disease is the major cause of death in chronic kidney disease patient as well as in patients on hemodialysis. Dyslipidaemia is highly prevalent in patients on maintenance haemodialysis which increases the risk for cardiovascular mortality. This study was designed to evaluate the lipid abnormalities, effect of atorvastatin on lipid profile and cardiovascular events in patients on maintenance hemodialysis.&#x0D; Methods: In this prospective clinical study, 55 end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis participated voluntarily. The study population was divided randomly into group-A (atorvastatin was prescribed) and group-B (without atorvastatin). We compared the lipid status and cardiovascular events of both groups after 6 months.&#x0D; Results: The two groups of patients were well matched in respect to baseline characteristics, history of risk factors and dialysis duration and session. Mean age of study population was about 48 years. Low density lipoprotein (LDL) cholesterol was reduced by 18.79%, total cholesterol was reduced by 9.32% and triglyceride was reduced by 22% in group-A. In group-A, high density lipoprotein (HDL) cholesterol was increased by 6% and it was reduced by 6% in group-B. In this study, myocardial ischemia/infarction on electrocardiogram (ECG) was present 22% in group-A and 14% in group-B at randomization. After 6 months, ischemia/infarction was found 33% in group-A and 25% in group-B. Statistically the ECG findings showed no significant changes after 6 months. In this study, mean ejection fraction (EF %) was 54% in group-A and 51% in group-B at 0 month, after 6 months atorvastatin group failed to show any significant change. In this study, after 6 months of statin therapy there was slight increase of serum glutamic pyruvic transaminase (16.13%) but that was not significant.&#x0D; Conclusion: In this study atorvastatin improved the lipid abnormalities significantly but a significant reduction of cardiovascular events was not achieved.&#x0D; Birdem Med J 2020; 10(1): 34-39

Atorvastatin inhibits endoplasmic reticulum stress through AMPK signaling pathway in atherosclerosis in mice.

Effect of atorvastatin inhibition of endoplasmic reticulum stress and amelioration of atherosclerosis through AMPK pathway were studied. Eight-week-old male apolipoprotein E-deficient (ApoE−/−) mice were fed with high-fat diet for 2 weeks and randomly divided into two groups: Atorvastatin treatment group was given atorvastatin (5 mg/kg/day) injection for a total of 6 weeks; control group was given the same dose of PBS through intraperitoneal injection for a total of 6 weeks. H&E staining was used to detect plaque size; immunohistochemical staining was used to detect T cells, macrophages and phospho-protein kinase-like ER kinase (phospho-PERK) in localized plaques. Proteins were extracted from mouse thoracic and abdominal aortic tissues. Western blot analysis was used to detect the protein expression levels of endoplasmic reticulum stress-related molecules phospho-eukaryotic initiation factor-2α (p-eIF2α), eukaryotic initiation factor (eIF2a), and sliced x-box binding protein 1 (sXBP-1). Cultured human umbilical vein endothelial cells (HUVECs), induced endoplasmic reticulum stress with human oxidized low density lipoprotein (ox-LDL), were treated with atorvastatin, AMPK agonist 5-amino-4-imidazolecarboxamide riboside-I-β-D-ribofuranoside (AICAR) and AMPK-DN that expressed a dominant-negative mutant of AMPK. Western blot analysis was used to test the expression levels of endoplasmic reticulum stress-related molecules p-elF2a and sXBP-1. The area of aortic plaques in atorvastatin group was obviously decreased, and the infiltrations of CD3+ T cells and macrophages in the localized plaques were reduced. The endoplasmic reticulum stress-related proteins sXBP-1 and p-eIF2a were significantly reduced. The results of immunohistochemistry also showed a significant decrease in the level of phospho-PERK (p-PERK) in atorvastatin group. The results in ox-LDL-induced HUVECs showed that atorvastatin inhibited ox-LDL-induced endoplasmic reticulum stress, and the AMPK agonist AICAR also had the same effect, which was offset by DN-AMPK treatment. Atorvastatin inhibits ER stress both in vitro and in vivo and this protective effect is mediated by AMPK activation.

Atorvastatin attenuates spinal cord injury by chronic fluorosis in rats.

The aim of the study was to explore the effect of atorvastatin on improvement of the function of the spinal cord in rats with chronic fluorosis. Sixty 3-month-old Wistar rats were separated randomly into three groups: normal group (N group), control group (C group) and atorvastatin group (A group). The Basso Beattie and Bresnahan scale and oblique board test showed that the rats in A group got higher score and better hind-limb motor function than C group. Immunohistochemistry and western blotting revealed that compared with N group, matrix metalloproteinase 9 (MMP-9) and p53 were highly expressed and myelin basic protein (MBP) was low expressed in spinal cord of C group. Meanwhile, MMP-9 and p53 expression were decreased and MBP was upregulated by atorvastatin compared with C group. In conclusion, the improvement of the function of the spinal cord in rats can be found when they were treated with atorvastatin.

Immune Modulatory Effects of Hypercholesterolemia: Can Atorvastatin Convert the Detrimental Effect of Hypercholesterolemia on the Immune System?

Many observations showed that hypercholesterolemia can disrupt immune response. Statin drugs that were used for the treatment of hypercholesterolemia patients can interfere in the regulation of the immune response and cytokine secretion. The primary aim of the current study was to investigate the immune response among treatment-naïve patients with hypercholesterolemia and healthy subjects. The secondary goal of the study was to determine whether atorvastatin can reverse the detrimental effect of hypercholesterolemia on the immune system. Peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients afflicted with hypercholesterolemia who were treatment-naïve along with 50 sex/age-matched hypercholesterolemia patients receiving atorvastatin, and 50 sex/age-matched healthy subjects. Quantitative PCR and ELISA methods were used for gene and protein expression analysis of T helper 1 (Th1) and Th2 related cytokines. Additionally, the expression of the cluster of differentiation (CD) markers on T, B, and natural killer (NK) cells was measured by flow cytometry method. The results showed that hypercholesterolemia and atorvastatin down-regulated the expression of Th1-related cytokines and elevated the levels of Th2-related cytokines. The expression of cell surface markers, CD25 and CD69, was significantly decreased in the treatment-naïve, and atorvastatin groups. It seems that atorvastatin is not able to repair the deleterious effects of hypercholesterolemia on the immune system. Moreover, elevated levels of cholesterol along with the administration of atorvastatin tilt the Th1/Th2 balance in favor of Th2 and reduce T cell activation.

Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence

BackgroundThere is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD.MethodsThis observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction.ResultsBaseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time.ConclusionsThis study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD.

Autophagy-endoplasmic reticulum stress inhibition mechanism of superoxide dismutase in the formation of calcium oxalate kidney stones

BackgroundNephrolithiasis is a common disease in urology, and its pathogenesis is associated with various factors. Recent studies have shown that reactive oxygen species (ROS) can promote autophagy in the formation of kidney stones and exacerbate kidney injury. Endoplasmic reticulum stress (ERS), a key factor in regulating intracellular environmental homeostasis, is also directly related to ROS production. Therefore, this study aimed to investigate the regulatory effect of superoxide dismutase (SOD) on autophagy-ERS response during the formation of calcium oxalate (CaOx) kidney stones in rats. MethodsThirty-two rats were randomly divided into four groups (n = 8): normal control group, stone model group, stone model with atorvastatin group, and stone model with diethyldithiocarbamic acid (DETC) group. Rat models of CaOx kidney stones were established by intragastric administration of 0.75 % ethylene glycol for 4 weeks. Kidney/body weight was used to assess renal enlargement. Renal function was assessed by measuring serum SOD, creatinine (CRE), and blood urea nitrogen (BUN) levels. The expression of autophagy-related proteins LC3B and BECN1 was detected through immunohistochemical staining. Meanwhile, the expression of autophagy-ERS response-related proteins LC3B, BECN1, p62, GRP78, and CHOP was detected using Western blot and RT-PCR. Renal tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (Kim-1) were determined through enzyme-linked immunosorbent assay. The apoptosis of renal tubular cells and the expression of their signature proteins cleaved Caspase-3, Bax and Bcl-2 were detected using Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Western blot assays, respectively. Crystal deposition and histological tissue injury were assessed through Von Kossa staining. ResultsCompared with the control group, the stone model group showed higher kidney/body weight ratio; evidently higher expression of autophagy-ERS response- and apoptosis-related proteins LC3B, BECN1, GRP78, CHOP, Bax and cleaved Caspase-3; and lower levels of p62, bcl-2 protein, and SOD. The stone model group also showed higher levels of apoptosis, serum CRE, BUN, NGAL, and Kim-1, as well as considerably greater crystal deposition and renal injury, than the control group. Atorvastatin reduced the levels of autophagy-ERS response, kidney injury, and crystal deposition, but they were increased by DETC. ConclusionEnhanced SOD activity can protect the kidneys by reducing autophagy-ERS response and CaOx kidney stone formation. Atorvastatin may be a new option for the prevention and treatment of nephrolithiasis.

Safety of High-Intensity Statins in the Veteran Population: Atorvastatin 40 to 80 mg Compared With Rosuvastatin 20 to 40 mg.

Background: High-intensity statin therapy is recommended in patients with clinical atherosclerotic cardiovascular disease (ASCVD) or at high risk of ASCVD. Current evidence demonstrates efficacy of high-intensity statin therapy in reducing major adverse cardiovascular events; yet the comparative safety profile between high-intensity statin agents remains unknown. In 2011, when atorvastatin became generic, the Veteran's Health Administration made the formulary switch from rosuvastatin to atorvastatin. Currently, rosuvastatin is generic; however, at the time of this study, it was still under patent. Objective: The primary objective was to determine if high-intensity atorvastatin compared with rosuvastatin is associated with an increased incidence of adverse drug reactions (ADRs) in the veteran population. Methods: A retrospective cohort study at James A. Haley Veterans' Hospital compared patients receiving rosuvastatin 20 to 40mg from January 2009 to November 2011 (n = 4,165) and atorvastatin 40 to 80mg from May 2012 to June 2016 (n = 5,852). Patients were excluded if they were nonadherent to statin therapy or had a documented ADR to atorvastatin prior to formulary switch. Results: A difference in overall ADR rates was found between atorvastatin and rosuvastatin groups (4.59% vs 2.91%; odds ratio [OR], 1.61; 95% CI, 1.29 to 2.00; P < 0.05). Statistically significant differences in abnormal liver transaminases (3.99% vs 1.39%; OR, 2.95; 95% CI, 2.21 to 3.94; P < 0.05) and statin-associated muscle symptoms (1.14% vs 0.5%; OR, 2.29; 95% CI, 1.39 to 3.74; P < 0.05) were identified between groups. Patients receiving rosuvastatin were on therapy 2.5 times longer before developing an ADR. Conclusion and Relevance: High-intensity atorvastatin compared with rosuvastatin is associated with an increased incidence of ADRs.

The effect of atorvastatin on cognition and mood in bipolar disorder and unipolar depression patients: A secondary analysis of a randomized controlled trial

ObjectivesStatins have recently been linked to having effects on cognition and mood in mood disorders, though results are mixed. In this paper, we use data from a recent randomized controlled trial (RCT) to examine the effect of statins on cognition and mood in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). MethodsThis is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial (n = 60) originally designed to examine the effect of atorvastatin (n = 27) versus placebo (n = 33) for lithium-induced diabetes insipidus in BD and MDD patients who were using lithium. For this analysis, the primary outcome was global cognition Z-score at 12-weeks adjusted for baseline. The secondary cognition outcomes were (1) Screen for Cognitive Impairment in Psychiatry (SCIP), and (2) executive function Z-score. The primary mood outcome (secondary outcome of this analysis) was depression relapse during 12-week follow-up (Mongomery Asberg Depression Rating Scale (MADRS) ≥10). The secondary mood outcomes were (1) relapse rate into a manic episode, and (2) relapse rate into any mood episode. ResultsAfter 12 weeks follow-up, atorvastatin and placebo groups did not differ in terms of global cognition Z-score (β = −0.009287 (−0.1698,0.1512), p-value = 0.91). Similarly, composite Z-scores for SCIP and executive functions did not differ significantly. Depression relapse during 12-week follow-up was not significantly different between the groups (χ2 (1) = 0.148, p-value = 0.70). Similarly, there was no difference between groups regarding relapse into mania. ConclusionIn BD and MDD patients with lithium-induced nephrogenic diabetes insipidus randomized to atorvastatin or placebo, we found no significant differences in cognition and mood outcomes at 12-week follow-up.