atorvastatin Lipitor
[Relationship Between Lipid Lowering and Changes of Hemostasis and Inflammation During Use of Statins in Non-ST Elevation Acute Coronary Syndrome]

[Article in Russian]

Pokrovskaia EV, Gratsianskii NA, Vaulin NA, Deev AD.

Research Institute for Physicochemical Medicine, Center of Atherosclerosis; ul. Malaya Pirogovskaya, 1a, 119828 Moscow, Russia.

AIM: To analyze relationship between changes of lipid levels and parameters of hemostasis and inflammation in a previously reported comparative study of some biological effects of pravastatin and atorvastatin in patients with non ST elevation acute coronary syndrome (NSTEACS). METHODS: Ninety aspirin and heparin treated patients with NSTEACS were randomized to open pravastatin 40 mg/day (n=31) and atorvastatin 10 (n=30) or 40 mg/day (n=29). At baseline, on days 7 and 14 we measured levels of thrombin-antithrombin complex (TAT), prothrombin fragments 1+2 (F1+2), D-dimer, von Willebrand factor (vWF) and C-reactive protein (CRP) and assessed platelet aggregation. Spearman correlation coefficients were calculated for mean deltas of all parameters {[(baseline - day 7) + (baseline - day 14)]/2} for all patients. The patients were divided into quartiles according to absolute LDL CH lowering by day 14. RESULTS: Levels of LDL and total CH significantly decreased in all groups (atorvastatin 40 mg/day >> atorvastatin 10 mg/day > pravastatin). Contrary to pravastatin the use of atorvastatin was associated with increases of F 1+2, TAT, and decrease of vWF. Platelet aggregation decreased only in atorvastatin 40 mg/day group (p<0.05) and CRP decreased in combined atorvastatin group (p<0.05). Most pronounced relationship existed between changes of lipid levels and vWF. Lowering of total and LDL CH correlated positively with decreases of vWF (r=0.25, p=0.018, and r=0.23, p=0.032, respectively) and quartile analysis showed that vWF decreased only in patients with marked LDL CH lowering (quartiles 3, 4). Negative correlation was found between changes of total CH and those of TAT (r=-0.22, p=0.039), and between changes of CRP and HDL CH (r=-0.24, p=0.03). TAT and F 1+2 levels significantly increased in those patients in whom LDL CH level <2.5 mmol/l was achieved by day 14 and tended to decrease in other patients. No relationship was found between changes of lipids and platelet aggregation. CONCLUSION: Rapid (in 14 days) changes of some parameters of hemostasis occurring during treatment of patients with NSTEACS with various statins were related to degree of lipid lowering possibly irrespective of a statin used. Most evident was relationship between changes of lipids and von Willebrand factor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15340345&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Atorvastatin enhances bone density in ovariectomized rats given 17beta-estradiol or human parathyroid hormone(1-34).

Kawane T, Terashima S, Kurahashi I, Yanagawa T, Yoshida H, Horiuchi N.

Department of Biochemistry, Ohu University School of Dentistry, Koriyama 963-8611, Japan.

We investigated the in vivo effect of atorvastatin on bone mineral density (BMD) in ovariectomized (OVX) rats. Eight-week-old female rats underwent either a sham operation or ovariectomy, and treatments with vehicle, atorvastatin, 17beta-estradiol (E2) and human parathyroid hormone(1-34) [hPTH(1-34)] were initiated 6 wk after the surgery. E2 (10 microg/kg) treatment for 12 wk significantly increased lumbar BMD (L2-L4), whereas atorvastatin did not affect lumbar BMD. The combination of atorvastatin (2 mg/kg) and E2 significantly enhanced the BMD of lumbar vertebrae (L2-L4) and femoral metaphyseal area (2/10-4/10 segments from the most proximal point) compared to that of either E2 or atorvastatin alone. A low dose 1 micro g/kg of hPTH (1-34) did not alter lumbar or femoral BMD, whereas a high dose 17.5 micro g/kg of the peptide significantly increased BMD. Concomitant injections of atorvastatin (2 mg/kg) with hPTH(1-34) (1 microg/kg) for 8 wk significantly enhanced the BMD of lumbar vertebrae and the metaphyseal area of the femur in OVX rats. These findings demonstrate that chronic administration of atorvastatin appears to modestly enhance the BMD of the lumbar vertebrae and femoral metaphysis of OVX rats treated with submaximal doses of E2 and hPTH(1-34).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15347837&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial.

Tsimikas S, Witztum JL, Miller ER, Sasiela WJ, Szarek M, Olsson AG, Schwartz GG; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators.

Vascular Medicine Program, Department of Medicine, University of California San Diego, 9500 Gilman Dr, BSB 1080, La Jolla, CA 92093-0682, USA. stsimikas ucsd.edu

BACKGROUND: Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoBxapoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (-33%), total apoB-OxPL (-29.7%), total apoB-IC IgG (-29.5%), and IgM (-25.7%) (P<0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus -3.9%, P<0.0001) and Lp(a) (8.8% versus -0.7%, (P<0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) (R=0.85, P<0.0001), consistent with previous data that Lp(a) binds OxPL. CONCLUSIONS: After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15353498&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Comparison of raloxifene and atorvastatin effects on serum lipids composition of healthy post-menopausal women.

Piperi C, Kalofoutis C, Lagogianni I, Troupis G, Kalofoutis A.

Department of Biological Chemistry, School of Medicine, University of Athens, Athens, Greece.

The aim of this study was to evaluate the effects of the selective oestrogen receptor modulator, raloxifene, and those of statin, atorvastatin, in reducing the cardiovascular risks associated with the post-menopausal status. A detailed study of serum lipid concentrations was performed in four groups of post-menopausal women receiving either placebo, raloxifene or atorvastatin alone or their combination for the period of three months. Group A (raloxifene) showed significant decrease in total cholesterol levels (P < 0.05) and an increase in phospholipids concentration (P < 0.05), followed by a marked reduction in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.01) and ApoB amounts (P < 0.001). Additionally, ApoA-I concentration was significantly increased (P < 0.01). Group B (atorvastatin) presented decreased cholesterol (P < 0.05) and triglycerides levels (P < 0.01), followed by elevated high-density lipoprotein cholesterol (HDL-C) concentration (P < 0.05) and low LDL-C amounts (P < 0.001). ApoA-I was significantly increased (P < 0.001) whereas ApoB was reduced (P < 0.001). The combined treatment in Group C (raloxifene and atorvastatin) showed significant changes in the majority of serum lipids. In particular, total cholesterol was reduced (P < 0.001), as well as triglycerides (P < 0.001) levels. Phospholipids were raised (P < 0.01) whereas LDL-C was reduced (P < 0.001) as was ApoB (P < 0.001). Furthermore, ApoA-I was elevated (P < 0.001). A further attempt to evaluate each treatment group was performed and the significance of these results is discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15362487&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms.

Castro MM, Rizzi E, Rascado RR, Nagassaki S, Bendhack LM, Tanus-Santos JE.

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, Brazil, 14049-900.

Statins have cholesterol-independent effects including an increased vascular nitric oxide (NO) activity and are commonly used by patients with cardiovascular disease. Such patients frequently have erectile dysfunction, which may be treated with sildenafil, a selective inhibitor of phosphodiesterase type 5. Since statins and sildenafil can activate the NO-cGMP pathway, we investigated whether pre-treatment with atorvastatin (0, 5 and 30 mg/kg/day) for 2 weeks affects sildenafil (1 pM-100 mM)-induced relaxation of aortic rings isolated from Wistar rats. We also examined the hemodynamic consequences of this interaction in Wistar rats. Plasma nitrite/nitrate (NOx) concentrations were determined using an ozone-based chemiluminescence assay. While pre-treatment with atorvastatin increased the potency of sildenafil-induced vasorelaxation (P<0.01), no differences were observed in the maximum sildenafil-induced relaxation. Pre-incubation of aortic rings with NG-nitro-L-arginine methyl ester (L-NAME) reversed atorvastatin-induced increase in the potency of sildenafil relaxation. In addition, pre-treatment with atorvastatin enhanced plasma NOx concentrations and sildenafil-induced hypotension and tachycardia (all P<0.05). These results suggest that atorvastatin increases the vascular sensitivity to sildenafil through NO-mediated mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15363994&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
[Cost-effectiveness of atorvastatin in the early treatment of acute coronary syndromes in Germany based on the MIRACL study]

[Article in German]

Lange AP, Szucs TD.

European Center of Pharmaceutical Medicine, Basel, Schweiz.

BACKGROUND AND PURPOSE: Cardiovascular diseases are the leading cause of death in Germany and have a huge impact on the resource consumption. Therefore, cost-effectiveness of medical therapies must be evaluated and taken into consideration. The purpose of this study is to assess the short-term healthcare costs associated with intensive lipid lowering with atorvastatin (Sortis, Pfizer) initiated within 24-96 h after the onset of acute coronary syndromes (ACS) in patients from Germany. STUDY DESIGN: Model-based, cost-effectiveness analysis. METHODS: Clinical outcome data from the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study and cost data were used to compare the total expected 16-week cost per patient on atorvastatin 80 mg/day versus placebo. Only direct costs were taken into consideration. All direct medical costs were based on the average values of 116 hospitals in Germany, which were published in December 2002. PERSPECTIVE: The perspective of the German hospitals for the year 2004 was taken. RESULTS: The total calculated cost was euro 1,750 per patient in the placebo cohort and euro 1,910 per patient in the atorvastatin cohort, resulting in incremental cost of euro 161 per patient in the atorvastatin group. The cost per event avoided was euro 4,195. Over 40% of the cost of atorvastatin treatment was offset within 16 weeks by the cost savings resulting from the reduction in the number of events in the atorvastatin cohort compared to the placebo cohort. The validity of this result was substantiated through extensive sensitivity analyses. CONCLUSION: The application of atorvastatin administered early after ACS is cost-effective, and the clinical benefits are available through marginal additional cost.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15372179&dopt=Abstract atorvastatin Lipitor