Dronedarone reduces arterial thrombus formation.
Dronedarone has been associated with a reduced number of first hospitalisation due to acute coronary syndromes. Whether this is only due to the reduction in ventricular heart rate and blood pressure or whether other effects of dronedarone may be involved is currently elusive. This study was designed to investigate the role of dronedarone in arterial thrombus formation. C57Bl/6 mice were treated with dronedarone and arterial thrombosis was investigated using a mouse photochemical injury model. Dronedarone inhibited carotid artery thrombus formation in vivo (P < 0.05). Thrombin- and collagen-induced platelet aggregation was impaired in dronedarone-treated mice (P < 0.05), and expression of plasminogen activator inhibitor-1 (PAI1), an inhibitor of the fibrinolytic system, was reduced in the arterial wall (P < 0.05). In contrast, the level of tissue factor (TF), the main trigger of the coagulation cascade, and that of its physiological inhibitor, TF pathway inhibitor, did not differ. Similarly, coagulation times as measured by prothrombin time and activated partial thromboplastin time were comparable between the two groups. Dronedarone inhibits thrombus formation in vivo through inhibition of platelet aggregation and PAI1 expression. This effect occurs within the range of dronedarone concentrations measured in patients, and may represent a beneficial pleiotropic effect of this drug.
Cardiovascular Center, University Hospital Zurich, Switzerland.
Alexander
A
Breitenstein
Susanna H M
SH
Sluka
Alexander
A
Akhmedov
Simona
S
Stivala
Jan
J
Steffel
Giovanni G
GG
Camici
Huy H
HH
Riem
Hans-Jurg
HJ
Beer
Jan-Dirk
JD
Studt
Firat
F
Duru
Thomas F
TF
Luscher
Felix C
FC
Tanner
D000638:Amiodarone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000378:metabolism; D000077764:Dronedarone; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000517:prevention & control*; D014914:Whole Blood Coagulation Time
D000889:Anti-Arrhythmia Agents; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D000077764:Dronedarone; D000638:Amiodarone