Thromb Haemost 2005; 94(01): 193-199
DOI: 10.1160/TH05-01-0067
Cell Signalling and Vessel Remodelling
Schattauer GmbH

Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia

Anetta Undas
1   Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
,
Magdalena Celinska-Löwenhoff
1   Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
,
Teresa B. Domagala
1   Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
,
Teresa Iwaniec
1   Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
,
Jerzy Dropinski
1   Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
,
Tomasz Löwenhoff
1   Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
,
Andrew Szczeklik
1   Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland
› Author Affiliations

This work was supported by a grant from the Polish Committee for Scientific Research (No. 3PO5B 16322). Merck Sharp and Dohme and Fournier Laboratoires have purchased some materials and assays and provided the drugs studied.
Further Information

Publication History

Received 26 January 2005

Accepted after resubmission 19 April 2005

Publication Date:
05 December 2017 (online)

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Summary

The aim of the study was to determine whether a short-term treatment with simvastatin or fenofibrate may result in beneficial anti-inflammatory and antithrombotic effects in patients with high risk of coronary artery disease. In a randomized, double-blind study, we compared markers of inflammation, thrombin formation and platelet activation in patients with LDL cholesterol >130 mg/dl assigned to receive simvastatin (40 mg/d; n=20) or micronised fenofibrate (160 mg/d; n=22) for 28 days. Simvastatin, but not fenofibrate, lowered C-reactive protein (CRP) by 32% on day 3 (p<0.001), while both drugs reduced CRP significantly on day 28. Interleukin-6, soluble CD40 ligand, and monocyte chemoattractant protein-1 levels decreased significantly (by 20 to 50%) in both treatment groups on days 3 and 28. Soluble cell adhesion molecules remained unchanged in both groups. Simvastatin and fenofibrate significantly lowered plasma concentrations of thrombin-antithrombin complexes on days and 28, but not platelet β-thromboglobulin (βTG) levels. Soluble P-selectin was lowered only in the simvastatin group. The total amount of thrombin generated at the site of microvascular injury also declined (by about 30%) as early as after 3 days of fenofibrate or simvastatin therapy, whereas βTG release was reduced only in the simvastatin group on days 3 and 28.All the effects were independent of the changes in lipid profiles. Our results suggest that statins and fibrates can exert antithrombotic and anti-inflammatory effects as early as after 3 days of therapy. However, in contrast to statins, fibrates have no influence on platelet function within one month of therapy.