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Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.

Hanna MS, Mohan P, Knabb R, Gupta E, Frost C, Lawrence JH - Ann. N. Y. Acad. Sci. (2014)

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).

View Article: PubMed Central - PubMed

Affiliation: Global Clinical Research, Research & Development, Bristol-Myers Squibb Company, Princeton, New Jersey.

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Kaplan–Meier curves for the primary efficacy and safety outcomes in the phase III warfarin-controlled trial of apixaban for stroke prevention in atrial prevention (ARISTOTLE trial). The primary efficacy outcome (Panel A) was stroke or systemic embolism. The primary safety outcome (Panel B) was major bleeding, as defined according to the criteria of the ISTH. Modified, with permission, from Granger et al.29
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fig02: Kaplan–Meier curves for the primary efficacy and safety outcomes in the phase III warfarin-controlled trial of apixaban for stroke prevention in atrial prevention (ARISTOTLE trial). The primary efficacy outcome (Panel A) was stroke or systemic embolism. The primary safety outcome (Panel B) was major bleeding, as defined according to the criteria of the ISTH. Modified, with permission, from Granger et al.29

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


Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.

Hanna MS, Mohan P, Knabb R, Gupta E, Frost C, Lawrence JH - Ann. N. Y. Acad. Sci. (2014)

Kaplan–Meier curves for the primary efficacy and safety outcomes in the phase III warfarin-controlled trial of apixaban for stroke prevention in atrial prevention (ARISTOTLE trial). The primary efficacy outcome (Panel A) was stroke or systemic embolism. The primary safety outcome (Panel B) was major bleeding, as defined according to the criteria of the ISTH. Modified, with permission, from Granger et al.29
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260137&req=5

fig02: Kaplan–Meier curves for the primary efficacy and safety outcomes in the phase III warfarin-controlled trial of apixaban for stroke prevention in atrial prevention (ARISTOTLE trial). The primary efficacy outcome (Panel A) was stroke or systemic embolism. The primary safety outcome (Panel B) was major bleeding, as defined according to the criteria of the ISTH. Modified, with permission, from Granger et al.29
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

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).

View Article: PubMed Central - PubMed

Affiliation: Global Clinical Research, Research & Development, Bristol-Myers Squibb Company, Princeton, New Jersey.

Show MeSH
Related in: MedlinePlus