Abstract
Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.
Highlights
Stroke is associated with nonvalvular atrial fibrillation (NVAF), occurring in a yearly average of 5% of untreated NVAF patients and equaling approximately 700,000 cases per year [1]
In the pivotal phase 3 clinical trials in patients with Venous thromboembolism (VTE), direct-acting oral anticoagulants (DOACs) were noninferior for the treatment of acute symptomatic VTE and were associated with significantly decreased bleeding risks compared with standard therapy (LMWH or unfractionated heparin followed by treatment with an overlapping vitamin K antagonist (VKA); see Supplemental Table 2) [29,30,31,32,33]
Four DOACs are available for the prevention of stroke in patients with NVAF and for the treatment of VTE
Summary
Stroke is associated with nonvalvular atrial fibrillation (NVAF), occurring in a yearly average of 5% of untreated NVAF patients and equaling approximately 700,000 cases per year [1]. Venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), occurs at a rate of 117 people per 100,000 personyears annually, with increased incidence in select patient populations [2, 3]. Both NVAF-related stroke and VTE are causes of significant economic burden. Dabigatran (Pradaxa; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT), rivaroxaban (Xarelto; Janssen Pharmaceuticals, Inc., Titusville, NJ), apixaban (Eliquis; Bristol-Myers Squibb Co., Princeton, NJ), and edoxaban (Savaysa (United States) and Lixiana (European Union and Japan); Daiichi Sankyo, Parsippany, NJ) are directacting oral anticoagulants (DOACs) that have been approved in many regions of the world for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE [13,14,15,16,17,18].
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