Apixaban: A Novel Oral Inhibitor of Factor Xa

Edith Nutescu, Pharm.D., FCCP

Disclosures

Am J Health Syst Pharm. 2012;69(13):1113-1126. 

In This Article

Place in Therapy

There is great clinical need for oral warfarin alternatives for the long-term prevention of and treatment of patients with VTE and arterial thromboembolism. Further, a convenient alternative to parenteral anticoagulants is needed. Warfarin is limited by its low therapeutic index, multiple food and drug interactions, and complex monitoring requirements.[8,9] Aspirin and aspirin plus clopidogrel are less effective than warfarin in decreasing the risk for stroke in patients with AF.[103]

Owing to the bleeding risk associated with vitamin K antagonist therapy, current recommendations for patients with AF are aspirin (for patients with no additional risk factors for stroke), aspirin or warfarin (for patients with one moderate-risk factor for stroke), and warfarin (for patients with any high-risk factor or more than two moderate-risk factors for stroke).[67,104] Emerging oral anticoagulants, such as apixaban, dabigatran, edoxaban, and rivaroxaban, have the potential to make anticoagulant treatment and prophylaxis more convenient, as they are available for oral administration in fixed doses, have short half-lives, and have a rapid onset of action. Since they produce a predictable anticoagulant response, there is no requirement for routine monitoring.

Based on results from the RE-LY trial, dabigatran was approved for reducing the risk of stroke in patients with nonvalvular AF in both the United States and Europe. The currently approved indications for apixaban, dabigatran, and rivaroxaban for each of the indications considered for apixaban in this article are summarized in Table 5. Based on the results from the ROCKET-AF trial,[82] in September 2011 a panel voted 9–2, with one abstention, to recommend that FDA approve rivaroxaban to prevent stroke in patients with nonvalvular AF.[111] Subsequently, in November 2011, FDA granted approval for rivaroxaban for this indication. Recent results from AVERROES[59] and ARISTOTLE[60,61] provide evidence supporting the efficacy and safety of long-term stroke prophylaxis with apixaban and rivaroxaban, respectively. A new drug application for apixaban for stroke prophylaxis in patients with nonvalvular AF was submitted to FDA in 2011.[22]

Apixaban is currently indicated in Europe for the prevention of VTE in patients who have undergone total knee replacement or total hip replacement. Apixaban is also being investigated in Phase III trials for the treatment of VTE, the prevention of VTE in hospitalized acutely ill medical patients, and the prevention of stroke and other thromboembolic events in patients with AF. It is unlikely that an indication for the prevention of ischemic events in patients with ACS will be pursued due to the unacceptable bleeding risk observed in APPRAISE-2.

The emergence of a multitude of oral anticoagulants will permit clinicians to better individualize anticoagulant therapy options by choosing the optimal agent and regimen based on individual patient needs, considering not only safety, efficacy, and the clinical setting but also patient age, ethnicity, renal status, the presence of liver disease, and concurrent medications. As each of these new medications reach the market, their labeling should provide guidance with respect to many of these issues. For example, labeling for dabigatran, rivaroxaban, and apixaban provides specific guidance regarding use in patients with renal or hepatic impairment.[17,18,40] In addition to the pharmacokinetic and clinical characteristics, drug affordability and the potential for long-term adherence to therapy must be considered for these new agents to succeed in providing safe, efficacious, and convenient therapeutic alternatives.

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