Bleeding Risk, Management and Outcome in Patients Receiving Non-VKA Oral Anticoagulants (NOACs)
- 1.1k Downloads
Modern direct-acting anticoagulants are rapidly replacing vitamin K antagonists (VKA) in the management of millions of patients worldwide who require anticoagulation. These drugs include agents that inhibit activated factor X (FXa) (such as apixaban and rivaroxaban) or thrombin (such as dabigatran), and are collectively known today as non-VKA oral anticoagulants (NOACs). Since bleeding is the most common and most dangerous side effect of long-term anticoagulation, and because NOACs have very different mechanisms of action and pharmacokinetics compared with VKA, physicians are naturally concerned about the lack of experience regarding frequency, management and outcome of NOAC-associated bleeding in daily care. This review appraises trial and registry (or “real-world”) data pertaining to bleeding complications in patients taking NOACs and VKA and provides practical recommendations for the management of acute bleeding situations.
KeywordsDabigatran Major Bleeding Rivaroxaban Apixaban Bleeding Risk
Conflict of interest statement
SW received speaker honoraria from Bayer Healthcare. TB received honoraria from Bayer and Boehringer Ingelheim. FNA received honoraria from Bayer, BMS and Leo Pharma. JBW received honoraria for lectures and advisory boards as well as research support from Bayer Healthcare, Boehringer Ingelheim, Daiichi-Sankyo and Pfizer. All authors declare that the content of the presented review is not influenced by the above-stated relations with the pharmaceutical industry.
- 8.Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11):1234–43.PubMedGoogle Scholar
- 9.Toth P, van Veen JJ, Robinson K, Maclean RM, Hampton KK, Laidlaw S, et al. Real world usage of PCC to “rapidly” correct warfarin induced coagulopathy. Blood Transfus Trasfus del sangue. 2013;11(4):500–5.Google Scholar
- 14.van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2014;12(3):320–8.CrossRefPubMedGoogle Scholar
- 17.Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol. 2011;57(2):173–80.CrossRefPubMedGoogle Scholar
- 20.Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–47.CrossRefPubMedGoogle Scholar
- 21.Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123(21):2363–72.CrossRefPubMedGoogle Scholar
- 22.Halvorsen S, Atar D, Yang H, De Caterina R, Erol C, Garcia D, et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014;35(28):1864–72.PubMedCentralCrossRefPubMedGoogle Scholar
- 23.Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H, Brighton TA, et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013;11(1):21.PubMedCentralCrossRefPubMedGoogle Scholar
- 24.Sorensen R, Gislason G, Torp-Pedersen C, Olesen JB, Fosbol EL, Hvidtfeldt MW, et al. Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study. BMJ Open. 2013;3(5). doi: 10.1136/bmjopen-2013-002758.
- 27.Beyer-Westendorf J, Ebertz F, Förster K, Gelbricht V, Michalski F, Köhler C, et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost. 2015;113(6). doi: 10.1160/TH14-11-0954.
- 34.Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y, et al. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP)—March 2013. Arch Cardiovasc Dis. 2013;106(6–7):382–93.CrossRefPubMedGoogle Scholar
- 41.Glund S, Moschetti V, Norris S, Stangier J, Schmohl M, van Ryn J, et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015;113(5):911–1157. doi: 10.1160/TH14-12-1080.CrossRefGoogle Scholar
- 52.Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): predictors, characteristics, and clinical outcomes. J Am Coll Cardiol. 2014;63(20):2141–7.CrossRefPubMedGoogle Scholar