Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era

Abstract

Background: Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation.

Methods: Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance.

Conclusion: NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism.

Keywords: anticoagulation; deep vein thrombosis; direct Factor Xa inhibitor; direct thrombin inhibitor; patient needs; pulmonary embolism; vitamin K antagonist.

Figure 1

The balance between the risk of recurrent venous thromboembolism and bleeding events. Notes: Data from Konstantinides et al and Kearon et al. Abbreviations: GI, gastrointestinal; VTE, venous thromboembolism.

Figure 2

Principal efficacy and safety results of Phase III clinical trials of novel oral anticoagulants for the acute treatment of venous thromboembolism and long-term prevention of recurrence. Notes: Data from the acute treatment of VTE are presented for the (A) pooled EINSTEIN DVT and EINSTEIN PE,,, (B) pooled RE-COVER I and RE-COVER II,, (C) AMPLIFY, and (D) Hokusai-VTE studies. Data from studies of extended treatment are also presented for the (A) EINSTEIN EXT, (B) RE-SONATE, and (C) AMPLIFY-EXT studies. Patients in the extension studies did not necessarily complete the equivalent acute treatment study first. ^aEfficacy data were derived during the 6-month study period; ^bsafety data were obtained from the start of any study drug. Abbreviations: bid, twice daily; CI, confidence interval; HR, hazard ratio; LMWH, low-molecular-weight heparin; NMCR, nonmajor clinically relevant; RR, relative risk; VKA, vitamin K antagonist; VTE, venous thromboembolism.