FDA Approved Drugs » 2012
Medical Areas: Cardiology/Vascular Diseases | Neurology
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Bristol-Myers Squibb
Approval Status: Approved December 2012
Treatment Area: stroke and systemic embolism resulting from nonvalvular atrial fibrillation
Eliquis (apixaban) is an orally available Factor Xa antagonist. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development.
Eliquis is specifically indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
Eliquis is supplied as a capsule for oral administration. The recommended dose for most patients is 5 mg taken orally twice daily. The recommended dose of Eliquis is 2.5 mg twice daily in patients with any two of the following characteristics:
> age 80 years, body weight <60 kg, serum creatinine is >1.5 mg/dL. When Eliquis is coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp, the recommended dose is 2.5 mg twice daily.
The FDA approval of Eliquis was based on two clinical trials, ARISTOTLE and AVERROES.
This multinational, double-blind study enrolled 18,201 subjects with nonvalvular atrial fibrillation (AF). The subjects were randomized to Eliquis 5 mg orally twice daily (or 2.5 mg twice daily in subjects meeting certain parameters- see above) or to warfarin . The trial was designed to compare the effects of Eliquis and warfarin on the risk of stroke and non-central nervous system (CNS) systemic embolism. The primary endpint was the non-inferiority of Eliquis to warfarin in reducing the risk of stroke (ischemic or hemorrhagic) and systemic embolism. Superiority of Eliquis to warfarin was also examined for the primary endpoint (rate of stroke and systemic embolism), major bleeding, and death from any cause. The subjects were followed for a median of 89 weeks. Eliquis was superior to warfarin for the primary endpoint of reducing the risk of stroke and systemic embolism (Eliquis: 212 subjects (1.27%) versus warfarin (265 subjects (1.60%); p=0.01). Eliquis also showed significantly fewer major bleeds than warfarin. Eliquis also resulted in a significantly lower rate of all-cause death (p = 0.046) than did treatment with warfarin, primarily because of a reduction in cardiovascular death, particularly stroke deaths. Non-vascular death rates were similar in the treatment arms.
This trial enrolled 5,598 subjects with nonvalvular atrial fibrillation thought not to be candidates for warfarin therapy. Subjects were randomized to treatment with Eliquis 5 mg orally twice daily (or 2.5 mg twice daily in selected patients) or aspirin 81 to 324 mg once daily. The primary objective of the study was to determine if Eliquis was superior to aspirin for preventing the composite outcome of stroke or systemic embolism. AVERROES was stopped early on the basis of a prespecified interim analysis showing a significant reduction in stroke and systemic embolism for Eliquis compared to aspirin that was associated with a modest increase in major bleeding.
The most common adverse events associated with the use of Eliquis are related to bleeding.
Mechanism of Action
Eliquis (apixaban) is an orally available Factor Xa antagonist. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Apixaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development.
Flaker GC, Eikelboom JW, Shestakovska O, Connolly SJ, Kaatz S, Budaj A, Husted S, Yusuf S, Lip GY, Hart RG Bleeding During Treatment With Aspirin Versus Apixaban in Patients With Atrial Fibrillation Unsuitable for Warfarin: The Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) Trial. Stroke 2012 Dec;43(12):3291-7
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators Apixaban versus warfarin in patients with atrial fibrillation. The New England Journal of Medicine 2011 Sep 15;365(11):981-92
For additional information regarding Eliquis or stroke and systemic embolism resulting from nonvalvular atrial fibrillation, please visit the Eliquis web page.