Role of Direct Oral Anticoagulants in the Management of Anticoagulation

Rajiv N. Thakkar, MD; Suman W. Rathbun, MD; Scott M. Wright, MD


South Med J. 2017;110(4):293-299. 

In This Article

Abstract and Introduction


For decades, vitamin K antagonists (VKAs) have been the oral treatment of choice for many thromboembolic conditions. The limitations of VKAs include the need for monitoring through blood testing, drug interactions, and narrow therapeutic windows. These shortcomings have led to the development of direct oral anticoagulants. These new oral agents act on specific targets in the coagulation cascade (eg, factor Xa, thrombin) and negate some of the shortcomings of VKAs. This article reviews the roles of dabigatran, rivaroxaban, apixaban, and edoxaban in stroke prevention in nonvalvular atrial fibrillation, for prevention of venous thromboembolism after orthopedic surgery, and in the treatment of venous thromboembolism. Direct oral anticoagulants are at least as efficacious and safe as traditional anticoagulation therapy.


Clinicians commonly encounter medical conditions that require anticoagulation. Venous thromboembolism (VTE) occurs in 1 to 2 of every 1000 individuals each year, with approximately 90,000 new or recurrent cases diagnosed each year in the United States.[1] The incidence of symptomatic VTE during the first 35 days after knee or hip surgery without VTE prophylaxis may be as high as 4.3%.[2] Atrial fibrillation (AF) is associated with stroke, particularly with higher CHADS2 (congestive heart failure, hypertension: blood pressure consistently >140/90 mm Hg [or treated hypertension on medication], age 75 years old and older, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism scores).[3]

For decades, vitamin K antagonists (VKAs) have been used as the oral agents for the prevention and treatment of VTE, as well as for stroke prevention in patients with nonvalvular AF (NVAF). VKAs can significantly reduce the incidence of recurrent VTE.[4] Similarly, VKA can decrease stroke risk by 60% in patients with AF compared with those who are not treated.[5] Despite their demonstrated effectiveness, the limitations of VKAs include narrow therapeutic windows, drug and dietary interactions, the need for regular monitoring through blood testing, and unpredictable pharmacologic responses. Heparin, low-molecular-weight heparin, and fundaparinux are effective for VTE prophylaxis and treatment but require subcutaneous injections or intravenous infusion, which may affect patient acceptance and compliance.[6,7] These shortcomings have translated into great efforts to discover alternative oral anticoagulants. These new anticoagulants act directly on specific clotting factors in the coagulation pathway, and therefore they have been termed direct oral anticoagulants (DOACs).

This narrative review includes details about the pharmacokinetics and pharmacodynamics of DOACs; a review of randomized controlled trials (RCTs) comparing DOACs with traditional anticoagulation therapy; a discussion of the safety, efficacy, and limitations of DOACs; details about off-label uses; and information relevant to cost considerations.