Role of orally available antagonists of factor Xa in the treatment and prevention of thromboembolic disease: focus on rivaroxaban.
Interpatient variability in the safety and efficacy of oral anticoagulation with warfarin presents several challenges to clinicians, thus underscoring the emergent need for new orally available anticoagulants with predictable pharmacokinetic and pharmacodynamic profiles and ability to target circulating clotting factors. Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome. At doses used in phase 2 and 3 clinical trials, rivaroxaban and apixaban demonstrated a predictable onset of effect, maximal plasma concentration, and half-life that was unaffected by age, renal, or hepatic disease. In clinical trials for the treatment and prevention of venous thromboembolism, rivaroxaban and apixaban produced equivalent or superior reductions in the development or progression of venous thromboembolism compared with either low molecular weight heparin or warfarin. Trials comparing the efficacy of rivaroxaban or apixaban to standard therapy for stroke prophylaxis in patients with atrial fibrillation are in process. Rivaroxaban, the sentinel compound in this class, is already approved in the European Union and Canada. It is likely to be approved for use in the United States in 2010.
Morell
Jason
J
Loyola University Medical Center, Maywood, IL 60153, USA.
Sullivan
Bridgette
B
Khalabuda
Marina
M
McBride
Brian F
BF
D000284:Administration, Oral; D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy; D001549:Benzamides / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D002986:Clinical Trials as Topic; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D009025:Morpholines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000069552:Rivaroxaban; D020521:Stroke / Q000188:drug therapy / Q000517:prevention & control; D013876:Thiophenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013923:Thromboembolism / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D001549:Benzamides; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013876:Thiophenes; C522181:apixaban; D014859:Warfarin; C543086:betrixaban; D000069552:Rivaroxaban