High doses of atorvastatin do not affect activity of prothrombinase in patients with acute coronary syndromes

Olivotti, Luca; Ghigliotti, G; Spallarossa, Paolo; Leslie, Sally J.; Rossettin, Pierfranco; Barsotti, A; Brunelli, Claudio

doi:10.1097/00001721-200206000-00007

Cited by 16 publications

(8 citation statements)

References 30 publications

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“…In a study of Bolaman et al [5] atorvastatin did not significantly change levels of hemoglobin, nor the number of white blood cells and platelets. Other data indicated that prothrombinase activity in patients with acute coronary syndromes is not influenced by highdose atorvastatin (80 mg/d) [22]. However, high-dose atorvastatin had no effect on major hemorheologic variables in our current investigation.…”

Section: Discussioncontrasting

confidence: 65%

High-dose atorvastatin treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine

Loo

Spring

Koppensteiner

2011

Clinical Hemorheology and Microcirculation

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Background: Statins are used for the treatment of hypercholesterolemia. Although they are well known to have pleiotropic effects, their dose-dependent influence on platelet aggregation, hemorheologic properties and the plasma levels of homocysteine in patients with peripheral arterial disease (PAD) has not been thoroughly investigated so far.Methods and results: From a total of 100 patients with PAD 48 patients were randomized to a treatment with atorvastatin 80 mg/d for six months, and 52 patients served as controls who continued their medication including statins in lower doses. At baseline and at six months' follow up we assessed platelet aggregation upon stimulation with ADP, collagen and epinephrine using light transmission aggregometry. Furthermore, we determined major hemorheologic variables as well as the plasma levels of homocysteine, folic acid, and vitamin B6 and B12. No patient had obtained folic acid or B vitamin supplement.Platelet aggregation upon agonist-induced stimulation did not differ between patients under high-dose atorvastatin therapy and controls at baseline and after six months (p > 0.05). All hemorheologic parameters (plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, platelets, leucocytes) measured at baseline and after six months were not significantly different between both groups, too. After therapy with 80 mg atorvastatin homocysteine levels were significantly elevated as compared with baseline values (p = 0.0007), whereas levels remained unchanged in the control group. Folic acid levels were higher in the patients receiving high-dose atorvastatin as compared with controls both at baseline (p = 0.002) and at six months' follow up (p = 0.034). No significant difference in vitamin B6 and B12 levels both at baseline and after six months could be detected in either group.Conclusions: Treatment with 80 mg atorvastatin did not affect platelet aggregation and major hemorheologic parameters. The finding of an increase of homocysteine plasma levels in the presence of rather elevated levels of folic acid needs further investigation.

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Section: Discussioncontrasting

confidence: 65%

High-dose atorvastatin treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine

Loo

Spring

Koppensteiner

2011

Clinical Hemorheology and Microcirculation

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“…24 On the other hand, statins, even in high doses, do not diminish prothrombinase activity, as serially measured by the plasma levels of prothrombin fragment 1±2 in patients with acute coronary syndromes. 25 Obviously, large randomized studies are needed to determine the clinical importance, validity, and meaningfulness of the proposed beneficial pleiotropic effects of statins. 26…”

Section: Study Resultsmentioning

confidence: 99%

Absence of Interaction Between Atorvastatin or Other Statins and Clopidogrel

Serebruany¹,

Midei²,

Malinin³

et al. 2004

Arch Intern Med

145

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“…Furthermore, CD40 ligation is associated with the induction of COX-2 in endothelial cells [12]. Statins, which besides lipidlowering properties also have anti-inflammatory and anti-thrombotic effects, have been shown to interfere with CD40/CD40L signaling at several levels [10,13,14].…”

Section: Introductionmentioning

confidence: 99%

CD40-ligand-dependent induction of COX-2 gene expression in endothelial cells by activated platelets: inhibitory effects of atorvastatin

Mosheimer

Kaneider²,

Feistritzer³

et al. 2005

Blood Coagulation &Amp; Fibrinolysis

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Increasing evidence shows the importance of platelet-endothelial cell interactions in the progression of atherosclerosis. Platelets contribute to coronary events both as major components of thrombi and as a triggering factor in inflammation that leads to plaque vulnerability. Recent data suggest that statins, besides their lipid-lowering properties, exert pleiotropic effects that may be beneficial in atherosclerosis. Whether activated platelets influence cyclooxygenase-2 (COX-2) expression in human umbilical vein endothelial cells (HUVEC), the effect of atorvastatin, and possible mechanisms were investigated. COX-2 gene expression in HUVEC was studied using real-time polymerase chain reaction. CD40 ligand surface expression of platelets was tested by fluorescence-activated cell sorting analyses. Activated platelets significantly up-regulated COX-2 gene expression in HUVEC. Co-incubation of platelets with atorvastatin was shown to reverse this up-regulation via reduction of CD40 ligand surface expression on platelets. Data suggest that atorvastatin influences CD40-CD40-ligand-dependent platelet-endothelial interaction and that this influence affects platelet-induced COX-2 expression in HUVEC.

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High doses of atorvastatin do not affect activity of prothrombinase in patients with acute coronary syndromes

Cited by 16 publications

References 30 publications

High-dose atorvastatin treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine

High-dose atorvastatin treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine

Absence of Interaction Between Atorvastatin or Other Statins and Clopidogrel

CD40-ligand-dependent induction of COX-2 gene expression in endothelial cells by activated platelets: inhibitory effects of atorvastatin

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