Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new atorvastatin research articles will be listed here shortly after becoming available to us.
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Medical research on atorvastatin
J Card Surg. 2008 Jul; 23(4): 312-320
Sodha NR, Boodhwani M, Ramlawi B, Clements RT, Mieno S, Feng J, Xu SH, Bianchi C, Sellke FW
Background/Aim: Atorvastatin has previously been shown to reduce the endogenous angiogenic response to chronic ischemia in a porcine model. One possible mechanism for this effect is reduced bioavailability of nitric oxide, a key mediator of angiogenesis, secondary to increased oxygen free radicals. We sought to determine if atorvastatin modulates oxidative stress in myocardial tissue. Methods: Dietary induction of hypercholesterolemia was performed over 20 weeks in Yucatan swine with treated animals receiving atorvastatin 3 mg/kg/day. Chronic myocardial ischemia was induced via surgical placement of an ameroid constrictor ring around the proximal circumflex artery at age 20 weeks, followed by tissue harvest at age 27 weeks. Myocardial levels of protein, lipid, and DNA biomarkers of oxidative stress, serum levels of 8-isoprostane, nitric oxide (NO) dependent, and independent coronary microvascular reactivity, as well as isotope-labeled microsphere myocardial perfusion analysis and histologic analysis for endothelial cell density was performed. Results: Atorvastatin treatment was associated with elevated levels of myocardial protein oxidation and lipid peroxidation. Conversely, serum oxidant stress biomarkers were not elevated. Atorvastatin treatment improved nitric oxide dependent and independent microvascular reactivity, and was associated with decreased perfusion in the ischemic myocardial territory. Conclusion: Treatment with atorvastatin was associated with increased levels of myocardial tissue protein and lipid oxidative stress biomarkers and a reduced functional endogenous angiogenic response, but improved coronary microvascular reactivity. Increased oxidative stress in tissues may play a role in the reduced angiogenic response seen with atorvastatin treatment in other studies.
Expanding roles for atorvastatin.
Drugs Today (Barc). 2008 Jun; 44(6): 455-71
Singh V, Deedwania P
Atherosclerosis, especially when manifested as coronary artery disease (CAD), continues to be the number one cause of mortality and morbidity in developed nations and will soon become so in developing countries. Survivors of an acute heart attack have an increased risk of illness and death that is 1.5-15 times greater than in the general population. Sudden death occurs in myocardial infarction (MI) survivors at a rate 4-6 times greater than in the general population. After an initial recognized MI, 25% of male and 38% of female survivors die within 1 year. Within 6 years after a recognized MI, 18% of men and 35% of women will have a second MI, 7% of men and 6% of women will suffer sudden death, and 22% of men and 46% of women will be disabled with heart failure. Aggressive secondary prevention, therefore, is the key to containing and reversing the "malignant" natural history of CAD, since patients with CAD or CAD risk equivalents are already in the "high risk" category according to the Adult Treatment Panel III (ATP III) of the National Cholesterol Education rogram (NCEP). Treatment of dyslipidemia, especially the reduction of low-density lipoprotein (LDL) cholesterol levels to below 100 mg/dl, was recommended by the 2001 NCEP-ATP Guidelines. In 2004, based on the increasing evidence from several major clinical trials between 2001 and 2004, the NCEP-ATP reaffirmed its LDL goal of < 100 mg/dl in patients with CAD or coronary disease risk equivalents (including multiple risk factors), with an optional LDL goal of < 70 mg/dl in very-high-risk patients (including patients with established coronary heart disease plus other highrisk conditions) Findings from major studies, such as the Treating to New Targets (TNT) study, the Scandinavian Simvastatin Survival Study (4S), the Collaborative Atorvastatin Diabetes Study (CARDS), the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial and, more recently, the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LAA), lend support to the idea that greater LDL cholesterol lowering than that achieved with standard doses of statins may be warranted in patients with CAD and metabolic syndrome, CAD and diabetes, CAD and congestive heart failure, and CAD and renal insufficiency. On the other hand, additional lipid reduction may also be warranted in patients with risk factors such as diabetes, hypertension or a history of stroke, but without manifest CAD and despite relatively normal cholesterol levels. These newer indications for statins, atorvastatin in particular, as part of more aggressive secondary and primary prevention, are reviewed in this paper.
Mitochondrial cholesterol contributes to chemotherapy resistance in hepatocellular carcinoma.
Cancer Res. 2008 Jul 1; 68(13): 5246-56
Montero J, Morales A, Llacuna L, Lluis JM, Terrones O, Basañez G, Antonsson B, Prieto J, García-Ruiz C, Colell A, Fernández-Checa JC
Cholesterol metabolism is deregulated in carcinogenesis, and cancer cells exhibit enhanced mitochondrial cholesterol content whose role in cell death susceptibility and cancer therapy has not been investigated. Here, we describe that mitochondria from rat or human hepatocellular carcinoma (HC) cells (HCC) or primary tumors from patients with HC exhibit increased mitochondrial cholesterol levels. HCC sensitivity to chemotherapy acting via mitochondria is enhanced upon cholesterol depletion by inhibition of hydroxymethylglutaryl-CoA reductase or squalene synthase (SS), which catalyzes the first committed step in cholesterol biosynthesis. HCC transfection with siRNA targeting the steroidogenic acute regulatory protein StAR, a mitochondrial cholesterol-transporting polypeptide which is overexpressed in HCC compared with rat and human liver, sensitized HCC to chemotherapy. Isolated mitochondria from HCC with increased cholesterol levels were resistant to mitochondrial membrane permeabilization and release of cytochrome c or Smac/DIABLO in response to various stimuli including active Bax. Similar behavior was observed in cholesterol-enriched mitochondria or liposomes and reversed by restoring mitochondrial membrane order or cholesterol extraction. Moreover, atorvastatin or the SS inhibitor YM-53601 potentiated doxorubicin-mediated HCC growth arrest and cell death in vivo. Thus, mitochondrial cholesterol contributes to chemotherapy resistance by increasing membrane order, emerging as a novel therapeutic niche in cancer therapy.
Gene Expr. 2008; 14(3): 149-58
Zhao Y, Chan MY, Zhou S, Heng CK
This study investigated the early and long-term effects of atherogenic diet on hepatic gene expression, and the restorative effects of atorvastatin in treating hypercholesterolemia. Two groups of female C57BL/6J mice were fed standard chow or atherogenic diet for 1-week early phase study and two other groups for 10 weeks. The fifth group had daily 10 mg/kg atorvastatin injections for 3 weeks from week 8 of the atherogenic diet. Gene expression profiling was carried out with Affymetrix GeneChips. One-week atherogenic diet elevated 38 and inhibited 127 gene expressions, while 10-week atherogenic diet elevated 165 and inhibited 281 genes by more than twofold. Atorvastatin could restore 78.2% and 68%, respectively, of the genes to normal levels. Genes in the Insig (insulin-induced gene)-SREBP (sterol regulatory element binding proteins) pathway were mostly inhibited by atherogenic diet at week 1 but elevated at week 10. Of these, 65.2% were restored by atorvastatin. In conclusion, lipid homeostatic mechanism coped well with short-term atherogenic diet. However, when such a diet was prolonged, the mechanism was no longer effective but entered into a pathological state in which lipogenic genes, especially those in the Insig-SREBP pathway, were upregulated. Atorvastatin could restore changes in the Insig-SREBP pathway that were induced by the atherogenic diet.
Enferm Infecc Microbiol Clin. 2008 Jun; 26(6): 325-9
Bottaro EG, Caravello O, Scapellato PG, Stambulian M, Vidal GI, Loggia V, Scapellato JL, Thompson F, Cassetti I
INTRODUCTION: Highly active antiviral therapy (HAART) results in a sharp decrease in HIV-related morbidity and mortality, but also induces adverse effects such as dyslipidemia, which is difficult treat because of drug interactions. Guidelines recommend lipid-lowering therapy with pravastatin or atorvastatin to reduce LDL cholesterol in these patients, and gemfibrozil or fenofibrate for treating hypertriglyceridemia. The use of statins in the management of dyslipidemia is complicated by drug interactions with some of the components of HAART. Rosuvastatin, a statin with minimal cytochrome P-450-mediated metabolism, could be an alternative option for this population. METHODS: Retrospective study to evaluate the efficacy and safety of rosuvastatin (10 mg/day) for 16 weeks in HAART-treated HIV-infected patients with dyslipidemia, and moderate to high cardiovascular risk. Results were analyzed with the Shapiro-Wilks, K-S Lilliefors, and sign tests. Percentages were analyzed with the chi-square test. RESULTS: Seventy-eight patients were started on rosuvastatin for dyslipidemia, 60 as single therapy. After 16 weeks of treatment, a significant median decrease was seen in both LDL-cholesterol and non-HDL cholesterol (31.3% reduction in LDL and 29.9% in non-HDL). The therapeutic goal for non-HDL was achieved in 65.8% of patients. The decrease in triglyceride levels was also significant (34.1%); 35% of subjects achieved the therapeutic goal. The drug was withdrawn in 2 patients because of myositis, and in 1 because of gastrointestinal intolerance. There were no differences in efficacy or toxicity between patients receiving protease inhibitors, non-nucleoside reverse transcriptase inhibitors, or fibrates. CONCLUSION: Rosuvastatin was safe and effective for treating dyslipidemia in HAART-treated HIV-infected patients. Results were similar to those observed in the HIV-uninfected population.
Drugs R D. 2008; 9(4): 243-250
Usharani P, Mateen AA, Naidu MU, Raju YS, Chandra N
BACKGROUND AND OBJECTIVE: Hyperglycaemia leads to increased oxidative stress resulting in endothelial dysfunction. ACE inhibitors, antioxidants and HMG-CoA reductase inhibitors (statins) have been shown to improve endothelial function. The aim of this study was to compare the effects of NCB-02 (a standardized preparation of curcuminoids), atorvastatin and placebo on endothelial function and its biomarkers in patients with type 2 diabetes mellitus. METHODS: A total of 72 patients with type 2 diabetes were randomized to receive NCB-02 (two capsules containing curcumin 150 mg twice daily), atorvastatin 10 mg once daily or placebo for 8 weeks. Endothelial function assessment was performed at baseline and post-treatment using digital volume plethysmography (salbutamol [albuterol] challenge test) to measure change in reflective index, an indicator of arterial vascular tone. Blood samples were similarly collected at baseline and post-treatment for estimations of malondialdehyde, endothelin-1 (ET-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFalpha). Pre-and post-treatment safety assessments were also conducted. ANOVA and paired t-test evaluations were used for comparison. RESULTS: A total of 67 patients completed the study. At baseline, there was no significant difference in the various parameters tested. In all three groups, the change in reflective index at baseline was
J Nephrol. 2008 May_June; 21(3): 283
Tse KC, Yung S, Tang CS, Tam S, Lai KN, Chan TM
No abstract.
Am Heart J. 2008 Jul; 156(1): 65-70
Tsai CT, Lai LP, Hwang JJ, Wang YC, Chiang FT, Lin JL
BACKGROUND: Increasing evidence suggests that atrial fibrillation (AF) is an inflammatory disease. Statins is an anti-inflammatory agent. The present study was conducted to test the efficacy of atorvastatin in preventing paroxysmal AF or atrial high rate episodes (AHEs) in patients with bradyarrhythmias and implantation of an atrial-based or dual-chamber pacemaker. METHODS: The effect of atorvastatin on time to the first attack of AF or AHE (> or =180 per minute and > or =1 or 10 minutes), which was accurately detected by pacemaker interrogation, was evaluated in an open-label prospective randomized design for 1 year of follow-up. RESULTS: Fifty-two patients (23 males, 70 +/- 13 years old) were randomized to the statin group (atorvastatin 20 mg/d) and 54 (25 males, 72 +/- 13 years old) to the nonstatin group. Event-free survivals from AHE > or =1 minute were not significantly different between the 2 groups (log-rank P = .410). However, patients in the nonstatin group were more likely to develop AHE > or =10 minutes than those in the statin group (log-rank P = .028). Atrial high rate episode > or =10 minutes occurred in 3 (5.8%) of 51 patients in the statin group after 1 year of follow-up, and 10 (19.2%) of 52 patients (odds ratio 0.26, P = .041) in the nonstatin group. The mean left atrial volume of the statin group was significantly lower than that of the nonstatin group at the end of follow-up (39.7 +/- 1.7 vs 43.7 +/- 1.9 mL, P < .0001). CONCLUSIONS: The present study demonstrated the efficacy of atorvastatin in preventing significant AF (> or =10 minutes) and left atrial enlargement in patients with bradyarrhythmias and implantation of a pacemaker.
J Pharm Biomed Anal. 2008 May 21;
Kadav AA, Vora DN
A stability indicating UPLC method was developed and validated for the simultaneous determination of atorvastatin, fenofibrate and their impurities in tablets. The chromatographic separation was performed on acquity UPLCtrade mark BEH C18 column (1.7mum, 2.1mmx100mm) using gradient elution of acetonitrile and ammonium acetate buffer (pH 4.7; 0.01M) at flow rate of 0.5ml/min. UV detection was performed at 247nm. Total run time was 3min within which main compounds and six other known and major unknown impurities were separated. Stability indicating capability was established by forced degradation experiments and separation of known degradation products. The method was validated for accuracy, repeatability, reproducibility and robustness. Linearity, LOD and LOQ was established for atorvastatin, fenofibrate and their known impurities.
Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death.
Neurosci Lett. 2008 Aug 8; 440(3): 260-4
Lee JK, Won JS, Singh AK, Singh I
Statins are inhibitors of HMG-CoA reductase that have been recently recognized as anti-inflammatory and neuroprotective drugs. Herein, we investigated anti-excitotoxic and anti-seizure effects of statins by using kainic acid (KA)-rat seizure model, an animal model for temporal lobe epilepsy and excitotoxic neurodegeneration. We observed that pre-treatment with Lipitor (atorvastatin) efficiently reduced KA-induced seizure activities, hippocampal neuron death, monocyte infiltration and proinflammatory gene expression. In addition, we also observed that lovastatin treatment attenuated KA- or glutamate-induced excitotoxicity of cultured hippocampal neurons. These observations suggest a potential for use of statin treatment in modulation of seizures and other neurological diseases associated with excitotoxicity.