Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia.
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 3 and 28, but not platelet beta-thromboglobulin (betaTG) 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 beta TG 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.
Undas
Anetta
A
Dept. of Medicine, Jagiellonian University School of Medicine, 8 Skawinska Str., 31-066 Cracow, Poland.
Celinska-Löwenhoff
Magdalena
M
Domagala
Teresa B
TB
Iwaniec
Teresa
T
Dropinski
Jerzy
J
Löwenhoff
Tomasz
T
Szczeklik
Andrew
A
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation; D002097:C-Reactive Protein / Q000737:chemistry; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D011345:Fenofibrate / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000473:pathology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007249:Inflammation; D050356:Lipid Metabolism; D008855:Microscopy, Electron, Scanning; D015539:Platelet Activation; D019821:Simvastatin / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D001620:beta-Thromboglobulin / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000924:Anticholesteremic Agents; D000991:Antithrombins; D008078:Cholesterol, LDL; D005343:Fibrinolytic Agents; D000960:Hypolipidemic Agents; D014280:Triglycerides; D001620:beta-Thromboglobulin; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin; D013917:Thrombin; D011345:Fenofibrate