The synthetic pentasaccharide fondaparinux: first in the class of antithrombotic agents that selectively inhibit coagulation factor Xa.
Fondaparinux (Arixtra), a synthetic pentasaccharide, is the first in a new class of antithrombotic agents that selectively inhibit coagulation factor Xa. In vitro experiments demonstrated that it is a selective inhibitor of factor Xa. In plasma, fondaparinux selectively binds to antithrombin, catalyzes factor Xa inhibition, and thereby inhibits thrombin generation. Its antithrombotic efficacy has been demonstrated in various animal models mimicking venous and arterial thrombosis. In humans, its pharmacokinetic profile is favorable, with a rapid onset of antithrombotic activity and an elimination half-life allowing a convenient once-daily dosing regimen. In several clinical trials, fondaparinux was more effective than the reference drug, enoxaparin, in preventing venous thromboembolism after hip fracture, major knee, and elective hip replacement surgeries. The overall reduction in the risk of venous thromboembolism ranged between 26.3 and 56.4%, depending on the trial. This superior efficacy was achieved without increasing the risk of clinically relevant bleeding. Fondaparinux also showed promising results in the treatment of patients with venous thromboembolism and acute coronary syndromes. Thus, it is now established that selective factor Xa inhibition is an efficient way to prevent venous thrombosis. The advent of fondaparinux offers an opportunity to improve substantially the management of venous thromboembolism.
Petitou
Maurice
M
Sanofi-Synthelabo, Toulouse, France. maurice.petitou@sanofi-synthelabo.com
Duchaussoy
Philippe
P
Herbert
Jean-Marc
JM
Duc
Gérald
G
El Hajji
Mohamed
M
Branellec
Jean-François
JF
Donat
François
F
Necciari
José
J
Cariou
Roger
R
Bouthier
Jean
J
Garrigou
Eric
E
D000818:Animals; D002986:Clinical Trials as Topic; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077425:Fondaparinux; D006801:Humans; D011134:Polysaccharides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013923:Thromboembolism / Q000188:drug therapy / Q000517:prevention & control
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D000077425:Fondaparinux