Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new lipitor research articles will be listed here shortly after becoming available to us.
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Medical research on lipitor
Cytometry A. 2008 Dec 2;
Mohler ER, Shi Y, Moore J, Bantly A, Hamamdzic D, Yoder M, Rader DJ, Putt M, Zhang L, Parmacek M, Wilensky RL
Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. The authors studied a diabetic swine model to determine if induction of DM adversely affects either bone marrow or circulating EPCs and whether a HMG-CoA reductase inhibitor (statin) improves development and recruitment of EPCs in the absence of cholesterol lowering. Streptozotocin was administered to Yorkshire pigs to induce DM. One month after induction, diabetic pigs were treated with atorvastatin (statin, n = 10), ezetimibe (n = 10) or untreated (n = 10) and evaluated for number of bone marrow and circulating EPCs and femoral artery endothelial function. There was no effect of either medication on cholesterol level. One month after induction of DM prior to administration of drugs, the number of bone marrow and circulating EPCs significantly decreased (P < 0.0001) compared to baseline. Three months after DM induction, the mean proportion of circulating EPCs significantly increased in the atorvastatin group, but not in the control or ezetimibe groups. The control group showed progressive reduction in percentage of flow mediated vasodilatation (no dilatation at 3 months) whereas the atorvastatin group and ezetimibe exhibited vasodilatation, 6% and 4% respectively. DM results in significant impairment of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin. (c) 2008 International Society for Advancement of Cytometry.
Scand J Clin Lab Invest. 2008 Dec 2; 1-7
Paulsen L, Holst LM, Bech JN, Starklint J, Pedersen EB
Objective. Improved cardiovascular survival during statin treatment might be due to effects in addition to cholesterol lowering. We hypothesize that sodium intake affects renal function and vasoactive hormones in atorvastatin-treated healthy subjects. Methods. In a randomized, placebo-controlled, double-blind, crossover study we measured the effect of a moderate change in sodium intake on glomerular filtration rate (GFR), blood pressure (BP), renal tubular function, plasma concentrations of vasoactive hormones and urinary excretion of aquaporin-2 (u-AQP2) in 22 healthy subjects. The subjects were randomized to standardized fluid intake and diet corresponding to the need for calories in the 4 days before each of the 2 examination days. In one of the periods they were randomized to receive sodium chloride tablets (2 g) thrice daily for 4 days. Two doses of atorvastatin (80 mg) were given; one at 2200 h the evening before the study day, the other at 0830 h in the morning. Results. 24-h urinary sodium excretion increased by 23 %. GFR and BP were unchanged. Sodium clearance, fractional excretion of sodium and u-AQP2 increased, whereas free water clearance decreased during high sodium intake. PRC and aldosterone were suppressed during the high sodium diet. Conclusions. A change in dietary sodium intake of approximately 100 mmol daily does not change GFR and BP in atorvastatin-treated healthy men. The lack of change in BP might reflect that the subjects studied were not sodium sensitive, or that atorvastatin treatment modified sodium sensitivity.
Modulation of human T cells signaling transduction by lovastatin.
Int J Cardiol. 2008 Nov 27;
Cheng SM, Lai JH, Yang SP, Tsao TP, Ho LJ, Liou JT, Cheng CC
Statins are applied clinically to treat hypercholesterolemia and proposed to have some kinds of anti-inflammatory properties for reducing the incidence of atherosclerosis-related cardiovascular events. However, it was rarely known about statins on the signal transduction on human primary T cells. To gain insight into the mechanism of statins on human T cells, we investigated the effects of both lovastatin and atorvastatin on activated human primary T cells. The human primary T cells from the blood of normal human beings were isolated. We found that lovastatin, but not atorvastatin, can dose-dependently inhibit cytokine production such as interleukin-2, interleukin-4, and interferon-gamma from activated human T cells. Neither lovastatin nor atorvastatin can regulate the TNF-alpha production on both activated human T cells and monocytes. Molecular investigation was performed that lovastatin, but not atorvastatin, could down-regulate both activator protein-1 and NF-kappaB DNA binding activities, assessed by electrophoretic mobility shift assay. Our observations may extend potential and differential therapeutic mechanisms of lovastatin with cell-mediated capacity to prevent or treat some of inflammation related diseases.
Mayo Clin Proc. 2008 Dec; 83(12): 1316-25
Jacobson TA, Wertz DA, Hoy T, Kuznik A, Grochulski D, Cziraky M
OBJECTIVE: To compare cardiovascular (CV) event rates and risk in patients without previous CV disease in whom atorvastatin or simvastatin was newly initiated in a managed care setting. PATIENTS AND METHODS: Patients aged 18 to 64 years in whom atorvastatin or simvastatin was newly initiated between January 1, 2003, and December 31, 2006, and who had no history of CV disease and at least 12 months of preindex and 3 months of postindex continuous eligibility in a managed care health plan, were identified using administrative claims from the HealthCore Integrated Research Database. Descriptive statistics were reported for sample characteristics. Unadjusted CV event rates were compared between treatment groups. A multivariate Cox proportional hazards model was developed to evaluate adjusted CV risk in all patients, as well as in a subset of patients with diabetes mellitus. RESULTS: A total of 168,096 patients in the atorvastatin group and 51,333 patients in the simvastatin group were analyzed. Mean+/-SD age was 50.2+/-9.0 years for patients using atorvastatin and 50.6+/-9.0 years for patients using simvastatin. Mean+/-SD follow-up time was 664.2+/-386.2 days for the atorvastatin group and 511.4+/-359.8 days for the simvastatin group. Mean+/-SD dose and mean+/-SD therapy duration for patients taking simvastatin were 29.1+/-15.1 mg and 188.6+/-236.3 days, respectively, compared with 16.8+/-11.1 mg and 241.8+/-292.0 days, respectively, for patients taking atorvastatin. Unadjusted CV event rates were lower with use of atorvastatin than with simvastatin (hazard ratio, 0.80; 95% confidence interval, 0.75-0.84; P
Pharmacoeconomic analysis of hypertriglyceridemia treatment at the medical institutions.
Yakugaku Zasshi. 2008 Dec; 128(12): 1783-9
Takahashi T, Saegusa Y, Takimoto Y, Shiragami M
It has been demonstrated that HMG-CoA reductase inhibitors effectively decrease low density lipoprotein and total cholesterol levels, and presently, HMG-CoA reductase inhibitors are most widely used in hyperlipidemia treatment. On the other hand, it has been demonstrated that fibrate agents decrease triglyceride levels more effectively compared to HMG-CoA reductase inhibitors. A cost-effectiveness study comparing fenofibrate, a fibrate agent, and atorvastatin was therefore conducted in hypertriglyceridemia patients. Referring to an analytical method published in the UK, the percentage of patients received fenofibrate and atorvastatin treatments at each dose level was estimated from prescription records at the medical institutions investigated. Changes in the total cholesterol and triglyceride values after the drug administration were investigated examining published reports. Based on the said data, the treatment effectiveness was measured by the percentage of patients who achieved the target lipid levels. The treatment costs were estimated based on the number of patients investigated and reimbursement prices of the drugs. The incremental cost-effectiveness ratio of fenofibrate in decreasing triglyceride levels was dominant over atorvastatin. The incremental cost-effectiveness ratio of atorvastatin in decreasing low density lipoprotein cholesterol levels was JPY 69911. This provides a model for choosing drug treatments that reflects clinical practices at medical institutions by substituting figures for individual cases.
J Lipid Res. 2008 Nov 30;
van Himbergen TM, Matthan NR, Resteghini NA, Otokozawa S, Ai M, Stein EA, Jones PH, Schaefer EJ
We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy. Measurements were performed in participants (n=135) at baseline and after 6 weeks on either rosuvastatin (40 mg/day) or atorvastatin (80 mg/day) therapy. Plasma sterols were measured using gas-liquid chromatography. Rosuvastatin and atorvastatin significantly (p
Int J Cardiol. 2008 Nov 28;
Xie RQ, Cui W, Liu F, Yang C, Pei WN, Lu JC
Although some data suggest that statins can improve cardiac mechanical function in some patients with chronic heart failure (CHF), the effects of long-term statin therapy on cardiac electrical instability remain unclear. We performed a randomized perspective analysis of the effects of 10 mg/d (statin group 1, n=40), 20 mg/d (statin group 2, n=38) of atorvastatin and controls (control group, n=41) on corrected QT intervals (QTc), corrected QT dispersion (QTcd) and cardiac function in patients with CHF secondary to coronary artery disease (CAD) for one year. At 6 and 12 months, the statin groups displayed lower QTc and QTcd compared with controls. The changes were becoming more distinct in statin group 2, (P
Arterioscler Thromb Vasc Biol. 2008 Nov 26;
Catalano G, Julia Z, Frisdal E, Vedie B, Fournier N, Le Goff W, Chapman MJ, Guerin M
OBJECTIVE: Therapeutic strategies to raise low plasma HDL-cholesterol levels, with concomitant normalization of the intravascular metabolism, physicochemical properties, and antiatherogenic function of HDL particles, are a major focus in atherosclerosis prevention. METHODS AND RESULTS: Patients displaying Type IIB hyperlipidemia (n=14) and healthy controls (n=11) were recruited. After drug washout, dyslipidemic patients first received atorvastatin (10 mg/d) for 6 weeks and subsequently torcetrapib/atorvastatin (60/10 mg/d) for the same period. Partial CETP inhibition markedly reduced supranormal CE transfer rates to normal levels from HDL3 (-58%; P
Cardiovasc Ther. 2008; 26(4): 253-61
Amudha K, Choy AM, Mustafa MR, Lang CC
Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow-mediated dilation (FMD) was measured in 56 first-degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age-, sex-, and BMI-matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA(IR)), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4-week double-blind, placebo-controlled trial. The FDRs had significantly impaired FMD (4.4 +/- 8.1% vs. 13.0 +/- 4.2%; P < 0.001), higher HOMA(IR) (1.72 +/- 1.45 vs. 1.25 +/- 0.43; P= 0.002), and elevated levels of plasma markers of inflammation-highly sensitive C-reactive protein (hsCRP) (2.6 +/- 3.8 mg/L vs. 0.7 +/- 1.0 mg/L; P= 0.06), interleukin (IL)-6 (0.07 +/- 0.13 ng/mL vs. 0.03 +/- 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 +/- 30.7 ng/mL vs. 238.2 +/- 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin-treated subjects when compared with the placebo-treated subjects (atorvastatin, from 3.7 +/- 8.5% to 9.8 +/- 7.3%; placebo, from 3.9 +/- 5.6% to 4.7 +/- 4.2%; P= 0.001). There were also reductions in the levels of IL-6 (0.08 +/- 0.02 ng/mL vs. 0.04 +/- 0.01 ng/mL; P < 0.001) and hsCRP (3.0 +/- 3.9 mg/L vs. 1.0 +/- 1.3 mg/L; P= 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.
A preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis.
Intensive Care Med. 2008 Nov 26;
Kruger PS, Freir NM, Venkatesh B, Robertson TA, Roberts MS, Jones M
OBJECTIVE: A lack of published pharmacokinetic data on statins in sepsis has prompted concerns about their safety and toxicity. This study determined single dose pharmacokinetics of Atorvastatin administered orally to acutely ill patients. DESIGN, SETTING AND PARTICIPANTS: A prospective open label study conducted in a tertiary referral centre on 5 healthy volunteers, 5 acutely ill patients admitted to the medical ward and a heterogeneous cohort of 25 critically ill patients admitted to an intensive care unit. INTERVENTION: All participants received a single oral dose of 20 mg of atorvastatin. MEASUREMENT AND RESULTS: Plasma pharmacokinetics of atorvastatin as measured by maximal plasma concentration (Cmax) and area under the curve (AUC) (0-24 h). Critically ill patients with sepsis had a significantly higher Cmax and AUC as compared to healthy volunteers [110.5(86.5) vs. 5.9(2.50) ng/ml, p < 0.01 and 1,051(810) vs. 67(48) ng h/ml (p < 0.0001)], respectively. Atorvastatin concentrations in the plasma of critically ill patients with sepsis remained supratherapeutic for up to 20 h after a single dose. The AUC was significantly higher for those patients on concomitant CYP 450 inhibitor therapy as compared to those patients not on inhibitors (1,518 +/- 793 vs. 584 +/- 540 ng h/ml, p = 0.0260). CONCLUSIONS: Very high plasma concentrations were achieved in intensive care patients with sepsis. This can only be partly explained by altered metabolism of atorvastatin. Further investigations are essential to better describe the pharmacokinetics of statins in various groups of critically ill patients. Caution should be exercised prior to adopting high dose regimens in patients with severe sepsis.