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FDA Approves Apixaban For Nonvalvular Atrial Fibrillation

By: Alexandra Alleva, PharmD candidate c/o 2013

As of December 28th, Bristol-Myers Squibb and Pfizer’s brand name oral anticoagulant, Eliquis® (apixaban), attained FDA approval.1  This occurred one month after its approval in  Europe and Canada, following longer than expected waits in the US due to further investigation requests by the FDA.2

The much-anticipated anticoagulant is indicated to reduce the risk of stroke and blood clots only in patients with nonvalvular atrial fibrillation , excluding those with prosthetic heart valves or valve associated disorders.1  These patient populations were not studied in apixaban’s clinical trials and therefore could not provide the data required to procure the expanded indications.3,4  In related news, the FDA recently issued a warning about Pradaxa® (dabigatran etexilate) failing to show safety in mechanical heart valve patients, exemplifying the importance of proper anticoagulant drug choice for such individuals.5

As the most common form of arrhythmia, atrial fibrillation afflicts nearly 3 million individuals in the United States, the number of which is only expected to rise in the coming years.6  A key component to treatment is the prevention of thrombosis and stroke with longstanding anticoagulation therapies, in cases where the benefit of medication outweighs the risk.  The disorder is more prevalent and severe in those with factors such as older age, cardiovascular disease, hypertension, diabetes, previous stroke or DVT history, and hyperthyroidism.6

Apixaban’s mechanism of action works in the body’s coagulation cascade to inhibit the activated form of clotting factor X, the enzymatic precursor to thrombin.  Thrombin, in turn, is the protein responsible for fibrinogen conversion to insoluble fibrin and, ultimately, clot formation.  Eliquis® will be available in 2.5 mg and 5 mg tablet strengths with a recommended twice daily dose.  It is the second  anti-Xa inhibitor to be released to the market.7

The introduction of Pradaxa®, as a direct thrombin inhibitor in 2010, and Xarelto® (rivaroxaban), the first of the factor Xa inhibitors in 2011, provided worthy alternatives to those patients with difficulty maintaining standard warfarin therapy.  However, despite their advantages over warfarin, like dietary and monitoring freedoms, there have been increased concern over bleeding events and lack of antidotes.8  In addition, the known drawback of these drugs is brand name pricing and affordability.  Therefore, neither have been able to overtake the prescription stronghold and market volume that warfarin continues to dominate.

Being a highly selective factor Xa inhibitor, studies have shown apixaban to be a very promising new generation oral anticoagulant.  The Phase III ARISTOTLE trial substantiated apixaban as a contender through demonstrated reductions in outcomes for stroke or systemic embolism and major bleeding events compared to warfarin.  These findings translated to a significant reduction in mortality.4  In the AVERROES trial, apixaban compared favorably to aspirin in terms of stroke and systemic embolism reduction in patients diagnosed with atrial fibrillation.3  Several other clinical trials have also displayed favorable comparison to enoxaparin in hip and knee replacement surgeries for the prophylaxis of venous thromboembolism, although further study is needed for this to be conclusive.9,10

As with all anticoagulants, the major risks associated with the use of apixaban are serious and life-threatening bleeding events, for which there is not yet a remedy in the new classes of anticoagulants.  Potential antidotes and reversal treatments for the novel anticoagulants are currently being researched.

Once a medication like Eliquis® is released to the public from a previously controlled clinical trial period, post-marketing reports and review usually will reveal both adverse and beneficial characteristics of the drug that were not originally established.  Such analyses prove helpful towards future developments, especially as targeted therapies become increasingly specific.  As a result, this will hopefully sustain the trend for discovering safer, more practical options to conventional treatment and optimize patient management in the field of anticoagulation.


  1. News Release: FDA approves Eliquis to reduce the risk of stroke, blood clots in patients with non-valvular atrial fibrillation. FDA Web site. Available at: Accessed December 28, 2012.
  2. O’Riordan, Michael. FDA Approves Apixaban to Prevent Stroke in Nonvalvular AF. Medscape Pharmacists News web site. Available at: Accessed December 28, 2012.
  3. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806-17.
  4. Granger CB, Alexander JH, Mcmurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-92.
  5. MedWatch: Pradaxa (dabigatran etexilate mesylate): Drug Safety Communication – Should Not Be Used in Patients with Mechanical Prosthetic Heart Valves. FDA web site. Available at: Accessed December 28, 2012.
  6. Division for Heart Disease and Stroke Prevention: Atrial Fibrillation Fact Sheet. CDC web site. Available at: Accessed December 28, 2012.
  7. Package insert. Eliquis (apixaban). Princeton, NJ: Bristol-Myers Squibb Company, New York, NY: Pfizer Inc; December 2012.
  8. Drug Safety and Availability: FDA Drug Safety Communication: Update on the risk for serious bleeding events with the anticoagulant Pradaxa (dabigatran). FDA web site. Available at: Accessed December 28, 2012.
  9. Lassen MR, Gallus A, Raskob GE, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010;363(26):2487-98.
  10. Lassen MR, Raskob GE, Gallus A, et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010;375(9717):807-15.
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