Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.
Bottom Line: 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.Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels.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).
Affiliation: Global Clinical Research, Research & Development, Bristol-Myers Squibb Company, Princeton, New Jersey.Show MeSH
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Mentions: The ARISTOTLE study achieved database lock in June 2011 after randomizing 18,201 patients. The mean CHADS2 score was 2.1, the mean age 70 years, and 43% of patients were warfarin naive. Study drug discontinuation was significantly less frequent in apixaban-treated than warfarin-treated patients (25.3% vs. 27.5%; P = 0.001) over a mean exposure of 1.7 years. Apixaban achieved superiority on SSE compared with warfarin (1.27% vs. 1.60% per year; HR 0.79; 95% CI 0.66–0.95; P = 0.01). The Kaplan–Meier plots of the primary efficacy outcome (Fig.2) show early and continued separation of the event curves, and correspond to a 21% relative risk reduction in SSE. The fact that the upper bound of the 95% CI was below both the prespecified noninferiority margin and less than 1 meant that the first two steps of the hierarchical testing sequence were satisfied in the intent-to-treat population: apixaban was not only noninferior, it was also superior to warfarin in the prevention of SSE.29
Affiliation: Global Clinical Research, Research & Development, Bristol-Myers Squibb Company, Princeton, New Jersey.