The extended use of thromboprophylaxis with direct oral anticoagulants (DOACs) for more than 30 days has been evaluated as an alternative for the standard duration thromboprophylaxis (7–10 days) with low molecular weight heparin in medically ill patients to reduce the risk of venous thromboembolism (VTE) after hospital discharge. EMBASE and MEDLINE were searched for studies evaluating extended duration thromboprophylaxis with DOACs versus standard thromboprophylaxis with enoxaparin in medically ill patients through October 2018. Search was limited to randomized-controlled trials. Symptomatic VTE, VTE-related death, and death from any cause, and major and clinically relevant non-major bleeding were used to assess the efficacy and safety, respectively. The Mantel–Haenszel random-effects model risk ratio (RR) and corresponding 95% CIs were calculated using the metan routine in Stata (version 14.2) to estimate the pooled treatment effects. Heterogeneity was assessed by the I2 statistics. Four studies met the inclusion criteria. DOACs were superior to enoxaparin in preventing symptomatic VTE (RR = 0.59, 95% CI 0.44–0.79). There were no significant differences in thromboprophylactic efficacy between extended and standard thromboprophylaxis as to VTE-related death (RR = 0.81, 95% CI 0.60–1.10) and death from any cause (RR = 0.98, 95% CI 0.87–1.09). Compared to the standard duration, extended thromboprophylaxis was associated with approximately two-fold greater risk of major (RR = 1.95, 95% CI 1.25–3.04), and clinically relevant non-major (RR = 1.81, 95% CI 1.29–2.53) bleeding. The superior efficacy was diminished by the unfortunate safety profile. Therefore, we continue to support both the American Society of Hematology (ASH) and the American College of Chest Physicians (ACCP) guidelines recommendation against the extended use of thromboprophylaxis beyond the hospital stay.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Cayley WE Jr (2007) Preventing deep vein thrombosis in hospital inpatients. BMJ 335(7611):147–151. https://doi.org/10.1136/bmj.39247.542477.AE
Cohen AT, Hamilton M, Bird A, Mitchell SA, Li S, Horblyuk R, Batson S (2016) Comparison of the non-VKA oral anticoagulants apixaban, dabigatran, and rivaroxaban in the extended treatment and prevention of venous thromboembolism: systematic review and network meta-analysis. PLoS ONE 11(8):e0160064. https://doi.org/10.1371/journal.pone.0160064
Toker S, Hak DJ (2011) Morgan SJ (2011) Deep vein thrombosis prophylaxis in trauma patients. Thrombosis. https://doi.org/10.1155/2011/505373
Al Yami MS, Kurdi S, Abraham I (2018) Direct oral anticoagulants for extended thromboprophylaxis in medically ill patients: meta-analysis and risk/benefit assessment. J Blood Med 9:25–34. https://doi.org/10.2147/jbm.S149202
Schunemann HJ, Cushman M, Burnett AE, Kahn SR, Beyer-Westendorf J, Spencer FA, Rezende SM, Zakai NA, Bauer KA, Dentali F, Lansing J, Balduzzi S, Darzi A, Morgano GP, Neumann I, Nieuwlaat R, Yepes-Nunez JJ, Zhang Y, Wiercioch W (2018) American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv 2(22):3198–3225. https://doi.org/10.1182/bloodadvances.2018022954
Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR (2012) Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl):e419S–e496S. https://doi.org/10.1378/chest.11-2301
Mahan CE, Fisher MD, Mills RM, Fields LE, Stephenson JJ, Fu AC, Spyropoulos AC (2013) Thromboprophylaxis patterns, risk factors, and outcomes of care in the medically ill patient population. Thromb Res 132(5):520–526. https://doi.org/10.1016/j.thromres.2013.08.013
Hull RD, Merali T, Mills A, Stevenson AL, Liang J (2013) Venous thromboembolism in elderly high-risk medical patients: time course of events and influence of risk factors. Clin Appl Thromb Hemost 19(4):357–362. https://doi.org/10.1177/1076029613481105
Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD, EXCLAIM study (2010) Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 153(1):8–18. https://doi.org/10.7326/0003-4819-153-1-201007060-00004
Spahn G (2002) Compliance with self-administration of heparin injections in outpatients. Eur J Trauma 28(2):104–109
Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI, Adopt Trial Investigators (2011) Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 365(23):2167–2177. https://doi.org/10.1056/NEJMoa1110899
Cohen AT, Spiro TE, Buller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V, Magellan Investigators (2013) Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 368(6):513–523. https://doi.org/10.1056/NEJMoa1111096
Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM, Apex Investigators (2016) Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med 375(6):534–544. https://doi.org/10.1056/NEJMoa1601747
Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE, Mariner Investigators (2018) Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med 379(12):1118–1127. https://doi.org/10.1056/NEJMoa1805090
Tao DL, Bien JY, DeLoughery TG, Shatzel JJ (2017) Extended thromboprophylaxis with direct oral anticoagulants for medical patients: a systematic review and meta-analysis. Blood 129(5):653–655. https://doi.org/10.1182/blood-2016-10-747931
Liew AY, Piran S, Eikelboom JW, Douketis JD (2017) Extended-duration versus short-duration pharmacological thromboprophylaxis in acutely Ill hospitalized medical patients: a systematic review and meta-analysis of randomized controlled trials. J Thromb Thrombolysis 43(3):291–301. https://doi.org/10.1007/s11239-016-1461-1
Conflicts of interests
All authors declare no conflicts of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Alshouimi, R.A., Al Rammah, S.M., Alzahrani, M.Y. et al. The use of direct oral anticoagulants for extended duration thromboprophylaxis in medically ill patients: a systematic review and meta-analysis. J Thromb Thrombolysis 48, 422–429 (2019). https://doi.org/10.1007/s11239-019-01900-2
- Venous thromboembolism
- Direct oral anticoagulants
- Medically ill patients