The international guidelines recommend the use of direct oral anticoagulants (DOACs) over vitamin K antagonists for anticoagulation long-term therapy in patients diagnosed with venous thromboembolism (VTE), and for stroke prevention in patients with non-valvular atrial fibrillation (AF). Efficacy and safety of DOACS have been extensively evaluated in large phase III trials. According to the product label, dose reductions of DOACs are recommended for patients with AF and renal impairment, low body weight and concomitant use of interfering medications. Except for Edoxaban, dose reductions of DOACs are not recommended in patients with VTE based on the same indications for AF patients. The aim of this article is to discuss the indication of a lower DOAC dose in some patients with VTE. Observational studies and randomized control trials (RCTs) show that patients with AF are usually older, more often have chronic diseases, and more often are treated with several concomitant medications, potentially increasing their haemorrhagic risk. Furthermore, many VTE patients need a shorter period of anticoagulation therapy than AF patients. In real-life studies, VTE patients treated with inappropriate DOAC doses present a higher rate of VTE recurrence, and the same risk of bleeding compared to those treated with the correct dose. In light of this evidence, the use of lower DOAC dose in patients with VTE does not appear reasonable and may be potentially dangerous.
Anticoagulation Direct oral anticoagulant Dose reduction Venous thromboembolism
This is a preview of subscription content, log in to check access.
Dr Francesco Dentali has acted as paid lecturer or board member and received grants and honoraria from Bayer, Sanofi, BMS/Pfizer, Boheringer, Alfa Wasserman and IL in the last 36 months for researches unrelated to the present study.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of human and animal rights
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent is not required.
Kearon C, Akl EA, Ornelas J et al (2016) Antithrombotic therapy for VTE disease. Chest guideline and expert panel report. Chest 149:315–352CrossRefPubMedGoogle Scholar
van Es N, Coppens M, Schulman S et al (2014) Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 124(12):1968–1975CrossRefPubMedGoogle Scholar
Kirchhof P, Benussi S, Kotecha D et al (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 18(11):1609–1678CrossRefPubMedGoogle Scholar
Prisco D, Ageno W, Becattini C et al (2017) Italian intersociety consensus on DOAC use in internal medicine. Intern Emerg Med 12(3):387–406CrossRefPubMedGoogle Scholar
Tran E, Duckett A, Fisher S et al (2017) Appropriateness of direct oral anticoagulant dosing for venous thromboembolism treatment. J Thromb ThrombolysisGoogle Scholar
Tellor KB, Patel S, Armbruster AL et al (2015) Evaluation of the appropriateness of dosing, indication and safety of rivaroxaban in a community hospital. J Clin Pharm Ther 40(4):447–451CrossRefPubMedGoogle Scholar
Di Pasquale G, Mathieu G, Maggioni AP et al (2013) Current presentation and management of 7148 patients with atrial fibrillation in cardiology and internal medicine hospital centers: the ATA AF study. Int J Cardiol 167(6):2895–2903CrossRefPubMedGoogle Scholar
Kakkar AK, Mueller I, Bassand JP et al (2013) Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD registry. PLoS ONE 8(5):e63479CrossRefPubMedPubMedCentralGoogle Scholar
Dentali F, Di Micco G, Giorgi Pierfranceschi M et al (2015) Rate and duration of hospitalization for deep vein thrombosis and pulmonary embolism in real-world clinical practice. Ann Med 47(7):546–554CrossRefPubMedGoogle Scholar
Verdecchia P, Angeli F, Bartolini C et al (2015) Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial fibrillation: a Bayesian meta-analysis approach. Expert Opin Drug Saf. 14(1):7–20CrossRefPubMedGoogle Scholar
Kline JA, Jimenez D, Courtney DM et al (2016) Comparison of four bleeding risk scores to identify Rivaroxaban-treated patients with venous thromboembolism at low risk for major bleeding. Acad Emerg Med 23(2):144–150CrossRefPubMedPubMedCentralGoogle Scholar
Schulman S, Kakkar AK, Goldhaber SZ et al (2014) RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 129(7):764–772CrossRefPubMedGoogle Scholar
Davidson BL, Verheijen S, Lensing AW et al (2014) Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 174(6):947–953CrossRefPubMedGoogle Scholar
Ageno W, Samperiz A, Caballero R et al (2015) Duration of anticoagulation after venous thromboembolism in real world clinical practice. Thromb Res 135(4):666–672CrossRefPubMedGoogle Scholar
Blanco-Molina A, Enea I, Gadelha T et al (2014) Sex differences in patients receiving anticoagulant therapy for venous thromboembolism. Medicine (Baltimore) 93(17):309–317CrossRefGoogle Scholar
Trujillo-Santos J, Di Micco P, Dentali F et al (2017) Real-life treatment of venous thromboembolism with direct oral anticoagulants: the influence of recommended dosing and regimens. Thromb Haemost 117(2):382–389CrossRefPubMedGoogle Scholar