Comparing efficacy and safety of plasmapheresis versus atorvastatin in pathological progression of atherosclerosis in a rodent model

Purpose: To evaluate the effect of plasmapheresis versus atorvastatin in pathological progression of atherosclerosis in a rodent model.Method: A total of 90 male adult rats of up to 300 g were randomly distributed in three groups (n = 30): group 1 (plasmapheresis up to 1.5 ml daily); group 2 (atorvastatin 0.1 mg/kg per day), and group 3 (hypercholesteremic rats). The following variables were assessed for 24 weeks: plasma and hepatic lipid and anti-oxidant profiles; atherosclerotic abrasions/lesions; coronary atherosclerosis/coronary stenosis score (CSS), composition of atherosclerotic lesions, incidence of xanthoma, arch and thoracic surface involvement including arch and thoracic area occupied by lesion; and thoracic aorta (I/M) ratio.Results: Compared to rats administered with atorvastatin, the rats treated with plasmapheresis had significantly greater improvement in levels of triglycerides (132 vs 124 mg/dl, p < 0.05), total cholesterol (201 vs 189 mg/dl, p < 0.05)), low-density lipoproteins (134 vs 123 mg/dl, p < 0.05)), very-low-density lipoprotein (11 vs 9 mg/dl, p < 0.05)) and high-density lipoprotein (36 vs 39 mg/dl, p < 0.05) levels. Plasmapheresis after 24 weeks of treatment improve CSS in all coronary arteries than atorvastatin (22 vs 24 respectively; p < 0.05. Furthermore, lesioned composition, I/M ratio and xanthoma incidence were significantly lower in plasmapheresis group than in atorvastatin group (p < 0.05).Conclusion: Plasmapheresis is a better alternative than atorvastatin in preventing pathological progression of atherosclerosis.

Pleiotropic Effects of Atorvastatin Result in a Downregulation of the Carboxypeptidase U System (CPU, TAFIa, CPB2) in a Mouse Model of Advanced Atherosclerosis

Statins (hydroxymethyl-glutaryl-CoA-reductase inhibitors) lower procarboxypeptidase U (proCPU, TAFI, proCPB2). However, it is challenging to prove whether this is a lipid or non-lipid-related pleiotropic effect, since statin treatment decreases cholesterol levels in humans. In apolipoprotein E-deficient mice with a heterozygous mutation in the fibrillin-1 gene (ApoE−/−Fbn1C1039G+/−), a model of advanced atherosclerosis, statins do not lower cholesterol. Consequently, studying cholesterol-independent effects of statins can be achieved more straightforwardly in these mice. Female ApoE −/−Fbn1C1039G+/− mice were fed a Western diet (WD). At week 10 of WD, mice were divided into a WD group (receiving WD only) and a WD + atorvastatin group (receiving 10 mg/kg/day atorvastatin +WD) group. After 15 weeks, blood was collected from the retro-orbital plexus, and the mice were sacrificed. Total plasma cholesterol and C-reactive protein (CRP) were measured with commercially available kits. Plasma proCPU levels were determined with an activity-based assay. Total plasma cholesterol levels were not significantly different between both groups, while proCPU levels were significantly lower in the WD + atorvastatin group. Interestingly proCPU levels correlated with CRP and circulating monocytes. In conclusion, our results confirm that atorvastatin downregulates proCPU levels in ApoE−/−Fbn1C1039G+/− mice on a WD, and evidence was provided that this downregulation is a pleiotropic effect of atorvastatin treatment.

Pioglitazone combined with atorvastatin promotes plaque stabilization in a rabbit model

Objective It is not yet clear whether plaque inflammation and cardiovascular events are reduced further when pioglitazone and atorvastatin are combined. Our study aimed to determine whether pioglitazone combined with atorvastatin can restrain the progression of atherosclerosis and promote plaque stabilization in a rabbit model Method and Result Thirty rabbits were randomly divided into an atherosclerosis group, an atorvastatin group, and an atorvastatin plus pioglitazone group. The atherosclerosis model was induced using balloon injury and feeding a high-fat diet. Plasma samples were then used to analyze glucose, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), high-sensitivity C-reactive protein (hs-CRP), and matrix metalloproteinase-9 (MMP-9). The area percentage of atherosclerotic plaques was analyzed by hematoxylin-eosin staining. The relative reductions in TG and LDL-C and the increase in HDL-C levels were significantly greater in the combination therapy group than in the atorvastatin monotherapy group (TG: −33.60 ± 7.17% vs −24.16 ± 8.04%, p < 0.001; LDL-C: −42.89 ± 1.63% vs −37.13 ± 1.35%, p < 0.001; and HDL-C: 25.18 ± 5.53% vs 10.43 ± 6.31%, p < 0.001). The relative reductions in hs-CRP and MMP-9 levels were significantly greater in the combination therapy group than in the atorvastatin monotherapy group (−69.38 ± 1.06% vs-53.73 ± 1.92%, p < 0.001; −32.77 ± 2.49% vs −13.36 ± 1.66%, p < 0.001). The area percentage of atherosclerotic plaques was significantly smaller in the atorvastatin group (47.75%, p < 0.05) and in the atorvastatin plus pioglitazone group (22.57%, p < 0.05) than in the atherosclerosis group (84.08%, p < 0.05) Conclusion We can thus conclude that the combination treatment of atorvastatin and pioglitazone provided additive benefits on inflammatory parameters and lipid metabolism. Pioglitazone combined with atorvastatin can further restrain the progression of atherosclerosis and promote plaque stabilization in a rabbit model.

Evaluation of Antyhipercholesterolemic Effect of Allium cepa L. var cepa in Atherogenic Induced Rats

Fermented onion is a type of onion that produced by heating onion bulbs at high temperature for 15 days by fermenter machine. This research is expected to produce new alternatives therapy for reducing cholesterol from onions especially Allium cepa L. var cepa. In this experimental laboratory used 25 male white rats that divided into five groups, group I: negatif control, group II: positif control (Atorvastatin), group III: 100 mg/Kg body weight (bw) of fermented onion extact, group IV: 200 mg/Kg bw of fermented onion extract and group V: 300 mg/Kg bw of fermented onion extract. The Rats was feeding by an atherogenic diet to makes them hypercholesterolemia before treatment for 7th days, 14th days and 21st days. All of data were analyzed by ANOVA method (significant 0,05). The result concludes that of all the doses tested, fermented onion extract of Allium cepa L. var cepa with a dose of 200 mg/Kg bw has the highest effect in decreasing total cholesterol levels of hypercholesterolemia rats (Rattus novergicus).

Effect of Dyslipidemia Therapy on Creatinine Kinase Activity Level in Patients with Heart Disease

Cardiovascular disease remains a significant health problem in the Asia Pacific region. Several studies have found that dyslipidemia is a cause of morbidity and mortality and requires high medical costs. Dyslipidemia is a risk factor for atherosclerosis. The most widely used therapy for dyslipidemia is statins. Statins often cause muscle disorders such as myalgia, myopathy, and rhabdomyolysis, which can cause death. A prospective cohort study design was carried out at Airlangga University Hospital, Surabaya, from April to November 2019. A total of 26 sample pairs containing 13 samples were treated with Atorvastatin, and 13 samples were treated with Simvastatin. The subjects were examined for the creatinine kinase activity level using enzymatic methods. The mean creatinine kinase levels in the atorvastatin group before and after treatment was 105.71 IU/L and 100.03 IU/L, respectively, because the subjects were diagnosed with acute coronary syndromes and blood was collected during acute conditions. Median creatinine kinase levels in the Simvastatin group were 85.5 IU/L before therapy and 118.1 IU/L after therapy, indicating significant differences in creatinine kinase levels before and after treatment. Simvastatin is very susceptible to certain drug interactions that can increase the concentration of statins in the serum. There were differences in levels of creatinine kinase activity before and after Simvastatin therapy but not Atorvastatin.

Atorvastatin is unlikely to prevent rheumatoid arthritis in high risk individuals: results from the prematurely stopped STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial

ObjectivesPersons at high risk of rheumatoid arthritis (RA) might benefit from a low-risk pharmacological intervention aimed at primary prevention. Previous studies demonstrated disease-modifying effects of statins in patients with RA as well as an association between statin use and a decreased risk of RA development. A randomised, double-blind, placebo-controlled trial investigated whether atorvastatin could prevent arthritis development in high-risk individuals.MethodsArthralgia patients with anticitrullinated protein antibody (ACPA) >3 xULN or ACPA and rheumatoid factor, without (a history of) arthritis, were randomised to receive atorvastatin 40 mg daily or placebo for 3 years. The calculated sample size was 220 participants. The primary endpoint was clinical arthritis. Cox regression analysis was used to determine the effect of atorvastatin on arthritis development.ResultsDue to a low inclusion rate, mainly because of an unwillingness to participate, the trial was prematurely stopped. Data of the 62 randomised individuals were analysed. Median follow-up was 14 (inner quartiles 6–35) months. Fifteen individuals (24%) developed arthritis: 9/31 (29%) in the atorvastatin group; 6/31 (19%) in the placebo group: HR 1.40, 95% CI 0.50 to 3.95.ConclusionsIn this small set of randomised high-risk individuals, we did not demonstrate a protective effect of atorvastatin on arthritis development. The main reason for the low inclusion was unwillingness to participate; this may also impede other RA prevention trials. Further research to investigate and solve barriers for prevention trial participation is needed.

The Effect of Low-Dose Atorvastatin on Inflammatory Factors in Patients with Traumatic Brain Injury: A Randomized Clinical Trial

Background: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality. Each year near 1.5 million Americans experience a TBI. Of which about 235,000 are hospitalized. Also, TBI claims 50 000 American lives each year. TBI causes mechanical damage to the blood-brain barrier and white blood cells (WBCs) entry to the brain. Objectives: The current study aimed to evaluate the efficacy of low-dose Atorvastatin on inflammatory factors in patients with traumatic brain injury (TBI). Methods: This double-blind, randomized clinical trial study was conducted in the ICU ward of Golestan Hospital in the city of Ahvaz (Iran) from April 2019-May 2020. Sixty patients with moderate to severe TBI were studied. Patients were randomly assigned into two groups of Atorvastatin and control. The main outcomes included the amount of CRP and ESR as well as white blood cells in the first 14 days of hospitalization. Glasgow Coma Score, the length of ICU stay, and the duration of mechanical ventilation were secondary outcomes. Results: The amount of CRP in the Atorvastatin group on the 14th day of hospitalization was significantly lower than those in the control group (31.99 ± 8.38 vs 59.65 ± 10.43) (P < 0.0001). On the same day, the Atorvastatin group had lower levels of ESR than the control group (14.28 ± 4.18 vs 25.57 ± 5.18) (P < 0.0001). The Atorvastatin group had significantly lower levels of white blood cells than the control group (5247.53 ± 751.93 vs 7143.94 ± 907.64, P < 0.0001). Glasgow Coma Score at the time of discharge from the ICU in the Atorvastatin group was more than control (14.06 ± 1.45 and 11.85 ± 0.75, respectively) (P < 0.05). A significant difference was found concerning the ICU stay between the two groups (P = 0.03). Conclusions: This study demonstrated that Atorvastatin could reduce the rate of inflammatory factors in TBI patients. The inflammatory condition of TBI patients heavily determines their prognosis. Inflammation leads to several reactions as well as interactions between different cells and chemical mediators. The Atorvastatin could reduce the rate of inflammatory factors and improved GCS in TBI patients.

COMPARISON OF PLASMA COAGULABILITY AFTER SHORT-TERM TREATMENT WITH ROSUVASTATIN VERSUS ATORVASTATIN IN UNSTABLE ANGINA PATIENTS

Statins are the integral medications for the management of patients with acute coronary syndrome including unstable angina (UA) with multiple pleiotropic effects. However, the influence of statins on the coagulation system is controversial. Our study aimed to explore the effects of atorvastatin and rosuvastatin in high doses on some coagulation parameters (prothrombin pool (PP) and soluble fibrin-monomer complexes (SFMC) concentration) after a 7-days follow-up period in patients with UA. We recruited 50 patients aged 55 to 70 years with progressive UA. Standard therapy according to ESC guidelines 2020 was recommended for all patients. Before treatment onset, they were divided into 2 groups: group A – 26 patients were prescribed atorvastatin, group R – 24 patients with rosuvastatin treatment. The blood samples to analyze the concentration of PP and SFMC were collected twice – before the treatment onset and 7 days after. We revealed significant decrease in PP concentration (p=0,02) and increase in SFMC concentration (p=0,01) in group A patients while there were no significant changes of investigated parameters (p=0,94, p=0,57 respectively) in group R. Additionally, we have noted significant negative correlation between baseline PP concentration and direction of PP changes (r=-0,803, p<0,001) as well as PP changes direction and SFMC concentration after treatment (r=-0,655, p<0,001). Thus, we may consider that atorvastatin and rosuvastatin are characterized by different influences on coagulation in patients with progressive UA with standard basic treatment. The rebound coagulation system activation after anticoagulant discontinuation is more pronounced in UA patients against a background of atorvastatin treatment in comparison with rosuvastatin.

Beneficial Effects of Adding Topical Atorvastatin 5% Cream to Topical Betamethasone 1% Ointment on Chronic Hand Eczema

Background: Hand eczema (HE) refers to a common inflammatory dermatological condition. Several studies have shown that statins may have anti-inflammatory effects. This study aimed at investigating the efficacy of adding topical atorvastatin to topical betamethasone in the treatment of chronic HE. Methods: This randomized, double-blind, placebo-controlled research was done between October 2017 and August 2018 in Hamadan, Iran. Of 130 cases treated for HE, 88 were randomly assigned to groups receiving either betamethasone 1% ointment plus atorvastatin 5% cream (n = 44) or betamethasone 1% ointment plus vehicle cream (n=44). Both groups applied their medications twice a day for 10 days. The primary outcome was changes in the severity of HE, assessed by hand eczema severity index (HECSI). The secondary outcomes were changes in itching evaluated via visual analogue scale (VAS) and quality of life examined through dermatology life quality index (DLQI). Results: Seventy-two out of 88 eligible cases completed the study. The mean HECSI scores decreased in both groups after the intervention, although the change in HECSI was greater in the atorvastatin group (adjusted mean difference [AMD]: 5.756; 95% CI: 5.168 to 6.344, P<0.001). The mean VAS scores decreased in both groups after the intervention, although the change in VAS was greater in the atorvastatin group (AMD: 10.535; 95% CI: 7.005 to 14.064, P<0.001). Treatment with topical atorvastatin was more effective in improving DLQI (AMD: 1.990; 95% CI: 1.821 to 2.158, P<0.001). Conclusion: Addition of topical atorvastatin to topical betamethasone is beneficial in treatment of chronic HE. Trial Registration: Identifier: IRCT2017070922965N10; https://www.irct.ir/.

Multiple functions of policosanol in elderly patients with dyslipidemia

Objective To determine the multiple functions of policosanol in elderly dyslipidemia patients. Methodology: There were 294 elderly dyslipidemia patients enrolled into this clinical study. They were randomly divided into four groups, as follows: 20 mg policosanol (group A, n = 64); 10 mg policosanol (group B, n = 72); 20 mg atorvastatin (group C, n = 91); and 10 mg policosanol + 20 mg atorvastatin (group D, n = 62). Plasma platelet count, platelet aggregation rate, circulating endothelial cell (CEC) count, high sensitivity C-reactive protein (hs-CRP), and carotid intima–media thickness (IMT) were measured before the study (week 0) and at weeks 12, 24, and 52. Results In group A, the platelet aggregation rate caused by adenosine diphosphate (ADP) after treatment was significantly decreased compared with before treatment (48.79% ± 20.29% vs. 40.37% ± 23.56%), but the arachidonic acid (AA)-induced platelet aggregation rates were similar. The platelet aggregation rates induced by AA and ADP in groups B, C, and D did not change significantly. CEC counts and hs-CRP and homocysteine levels in all groups after treatment were significantly lower compared with before treatment, but carotid IMTs were similar. Conclusion Policosanol regulates blood lipid levels and improves endothelial cell function, and it could delay the progress of atherosclerosis. Trial registration number: ChiCTR-RRC-17013396 (retrospectively registered).