A comprehensive evaluation of apixaban in the treatment of venous thromboembolism

ABSTRACT

Introduction: The emergence of the direct oral anticoagulants (DOACs) offers patients more convenient and accessible alternatives to warfarin or parenteral agents for the treatment of venous thromboembolism (VTE). Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is approved for the acute treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) as well as for the reduction in the risk of recurrent DVT and PE following initial therapy.

Areas covered: This article reviews results from preclinical and healthy volunteer studies, large phase III trials evaluating the safety and efficacy of apixaban, as well as key studies that led to apixaban’s current licensing. This review also will provide an overview of special populations where future areas of research are needed.

Expert commentary: Apixaban offers several advantages over historical therapy for the treatment and secondary prevention of VTE. However, there are some populations in which the use of apixaban has not been extensively studied such as patients >75 years old, or those with cancer, low or high body weight, or poor renal function. Likewise, there is a dearth of data on pediatric patients and patients with a history of heparin-induced thrombocytopenia or identified forms of thrombophilia. Additional comparator studies on anticoagulation reversal involving andexanet alfa are also necessary to further assess its hemostatic efficacy and prothrombotic risk.

KEYWORDS:

• Anticoagulation
• apixaban
• bleeding
• direct oral anticoagulant
• prevention
• treatment
• venous thromboembolism

Article Highlights

• Apixaban’s main advantages over warfarin are rapid onset of action, predictable pharmacologic and pharmacodynamic properties, few drug–drug interactions, low bleeding risk, and stable plasma concentrations throughout the dosing interval

• Large head-to-head trials directly comparing the efficacy, safety or tolerability of apixaban with the other DOACs for the primary treatment and secondary prevention of VTE are needed to differentiate their strenghs and identify any superiorities.

• Direct comparator trials exploring the relative efficacy and safety of andexanet in relation to prothrombin complex concentrates, placebo or no reversal, and reversal agents under development such as ciraparantag, must be performed to justify the high costs of andexanet alfa and define its place in anticoagulation reversal

• Use of apixaban in patients with reduced renal function has been established, but more studies are needed in obesity, oncology, HIT and pediatrics to establish safety and efficacy

• Insurance coverage and out-of-pocket cost of apixaban remains unmanageable for a proportion of patients which must be addressed on a national level

Declaration of interest

R. Rosovsky reports institutional research grant support from Janssen Pharmaceuticals and Bristol Meyer Squibbs and advisory/consult for Dova Pharmaceuticals, Portola, Janssen Pharmaceuticals, and Bristol Meyer Squibbs. H Al-Samkari is a consultant to Agios and Dova Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.