학술논문

Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.
Document Type
Article
Source
Annals of the New York Academy of Sciences. Nov2014, Vol. 1329 Issue 1, p93-106. 14p. 1 Chart, 5 Graphs.
Subject
*PYRIDONE
*ANTICOAGULANTS
*STROKE prevention
*ATRIAL fibrillation
*DRUG development
*CLINICAL pharmacology
*BLOOD coagulation factor X
*PATIENTS
Language
ISSN
0077-8923
Abstract
The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk. Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels. Our discussion here focuses on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation (NVAF). Supporting this indication, a pair of registrational trials was conducted that enrolled the full spectrum of patients who, by guidelines, were eligible for anticoagulation. In the AVERROES study of patients who were unsuitable for warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke or systemic embolism (SSE), without a significant increase in major bleeding (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the rates of SSE, MB, and all-cause mortality. Overall, these studies have demonstrated a substantially favorable benefit-risk profile for apixaban over warfarin and aspirin in NVAF. [ABSTRACT FROM AUTHOR]