Subscribe to RSS
DOI: 10.1055/s-0036-1582124
Update on Anticoagulation: What the Interventional Radiologist Needs to Know
Publication History
Publication Date:
10 May 2016 (online)
Abstract
The novel oral anticoagulants (NOACs) represent a major advance in the treatment of patients with nonvalvular atrial fibrillation and venous thromboembolism (VTE). They have several advantages over vitamin-K antagonists such as warfarin, including more predictable pharmacokinetics and improved safety, particularly with fatal bleeding and intracranial hemorrhage. However, several issues remain surrounding the use of NOACs in certain subpopulations and with the approach to reversal. The periprocedural management of anticoagulation with these relatively new agents can also present several challenges. This article reviews the basic pharmacology, efficacy, and safety of these drugs. Several populations at higher risk for complications with use of NOACs are discussed, including those undergoing procedures. Finally, several target-specific reversal agents have either received FDA approval or likely will be approved in the near future; these agents and their roles in the approach to anticoagulation reversal will also be discussed.
-
References
- 1 McMahon BJ, Kwaan HC. The new or non-vitamin K antagonist oral anticoagulants: what have we learned since their debut. Semin Thromb Hemost 2015; 41 (2) 188-194
- 2 Palladino M, Merli G, Thomson L. Evaluation of the oral direct factor Xa inhibitor—betrixaban. Expert Opin Investig Drugs 2013; 22 (11) 1465-1472
- 3 Linkins LA, Dans AL, Moores LK , et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e495S-e530S
- 4 Eikelboom JW, Weitz JI. New anticoagulants. Circulation 2010; 121 (13) 1523-1532
- 5 Eisert WG, Hauel N, Stangier J, Wienen W, Clemens A, van Ryn J. Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol 2010; 30 (10) 1885-1889
- 6 Weitz JI. New oral anticoagulants in development. Thromb Haemost 2010; 103 (1) 62-70
- 7 Liesenfeld KH, Lehr T, Dansirikul C , et al. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial. J Thromb Haemost 2011; 9 (11) 2168-2175
- 8 Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillón E. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. Eur J Haematol 2015; 95 (5) 389-404
- 9 Beyer-Westendorf J, Gelbricht V, Förster K , et al. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J 2014; 35 (28) 1888-1896
- 10 Krishnamoorthy A, Sherwood MW, Lopes RD, Becker RC. The periprocedural management of novel oral anticoagulants in patients with nonvalvular atrial fibrillation: rationale and a summary of the available evidence from phase 3 clinical trials. Am Heart J 2015; 169 (3) 315-322
- 11 Mar PL, Familtsev D, Ezekowitz MD, Lakkireddy D, Gopinathannair R. Periprocedural management of anticoagulation in patients taking novel oral anticoagulants: Review of the literature and recommendations for specific populations and procedures. Int J Cardiol 2016; 202: 578-585
- 12 Llau JV, Ferrandis R. New anticoagulants and regional anesthesia. Curr Opin Anaesthesiol 2009; 22 (5) 661-666
- 13 Connolly SJ, Ezekowitz MD, Yusuf S , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
- 14 Granger CB, Alexander JH, McMurray JJ , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
- 15 Patel MR, Mahaffey KW, Garg J , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
- 16 Giugliano RP, Ruff CT, Braunwald E , et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
- 17 Schulman S, Kearon C, Kakkar AK , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
- 18 Schulman S, Kakkar AK, Goldhaber SZ , et al; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014; 129 (7) 764-772
- 19 Bauersachs R, Berkowitz SD, Brenner B , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
- 20 Büller HR, Prins MH, Lensin AW , et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297
- 21 Agnelli G, Buller HR, Cohen A , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (9) 799-808
- 22 Büller HR, Décousus H, Grosso MA , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
- 23 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975
- 24 Gómez-Outes A, Terleira-Fernández AI, Lecumberri R, Suárez-Gea ML, Vargas-Castrillón E. Direct oral anticoagulants in the treatment of acute venous thromboembolism: a systematic review and meta-analysis. Thromb Res 2014; 134 (4) 774-782
- 25 Agnelli G, Buller HR, Cohen A , et al; PLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368 (8) 699-708
- 26 Romualdi E, Donadini MP, Ageno W. Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study). Expert Rev Cardiovasc Ther 2011; 9 (7) 841-844
- 27 Schulman S, Kearon C, Kakkar AK , et al; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368 (8) 709-718
- 28 Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillón E. Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review. Vasc Health Risk Manag 2014; 10: 627-639
- 29 Gómez-Outes A, Terleira-Fernández AI, Suárez-Gea ML, Vargas-Castrillón E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ 2012; 344: e3675
- 30 Eriksson BI, Dahl OE, Rosencher N , et al; RE-MODEL Study Group. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007; 5 (11) 2178-2185
- 31 Eriksson BI, Dahl OE, Rosencher N , et al; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370 (9591) 949-956
- 32 Eriksson BI, Borris LC, Friedman RJ , et al; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358 (26) 2765-2775
- 33 Lassen MR, Ageno W, Borris LC , et al; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358 (26) 2776-2786
- 34 Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM ; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010; 363 (26) 2487-2498
- 35 Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P ; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010; 375 (9717) 807-815
- 36 Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139 (11) 893-900
- 37 Kearon C, Akl EA, Comerota AJ , et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e419S-e494S
- 38 Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014; 124 (15) 2450-2458
- 39 Beyer-Westendorf J, Förster K, Pannach S , et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124 (6) 955-962
- 40 Dobesh PP, Fanikos J. Direct oral anticoagulants for the prevention of stroke in patients with nonvalvular atrial fibrillation: understanding differences and similarities. Drugs 2015; 75 (14) 1627-1644
- 41 Sardar P, Chatterjee S, Chaudhari S, Lip GY. New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 2014; 62 (5) 857-864
- 42 Eikelboom JW, Wallentin L, Connolly SJ , 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) 2363-2372
- 43 Lee AY, Levine MN, Baker RI , et al; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 (2) 146-153
- 44 Wanek MR, Horn ET, Elapavaluru S, Baroody SC, Sokos G. Safe use of hemodialysis for dabigatran removal before cardiac surgery. Ann Pharmacother 2012; 46 (9) e21
- 45 Chen BC, Sheth NR, Dadzie KA , et al. Hemodialysis for the treatment of pulmonary hemorrhage from dabigatran overdose. Am J Kidney Dis 2013; 62 (3) 591-594
- 46 Liotta EM, Levasseur-Franklin KE, Naidech AM. Reversal of the novel oral anticoagulants dabigatran, rivoraxaban, and apixaban. Curr Opin Crit Care 2015; 21 (2) 127-133
- 47 Ebright J, Mousa SA. Oral anticoagulants and status of antidotes for the reversal of bleeding risk. Clin Appl Thromb Hemost 2015; 21 (2) 105-114
- 48 Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011; 124 (14) 1573-1579
- 49 Schiele F, van Ryn J, Canada K , et al. A specific antidote for dabigatran: functional and structural characterization. Blood 2013; 121 (18) 3554-3562
- 50 Glund S, Moschetti V, Norris S , 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) 943-951
- 51 Glund S, Stangier J, Schmohl M , et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet 2015; 386 (9994) 680-690
- 52 Pollack Jr CV, Reilly PA, Bernstein R , et al. Design and rationale for RE-VERSE AD: A phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost 2015; 114 (1) 198-205
- 53 Pollack Jr CV, Reilly PA, Eikelboom J , et al. Idarucizumab for Dabigatran Reversal. N Engl J Med 2015; 373 (6) 511-520
- 54 Lu G, DeGuzman FR, Hollenbach SJ , et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013; 19 (4) 446-451
- 55 Siegal DM, Curnutte JT, Connolly SJ , et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med 2015; 373 (25) 2413-2424
- 56 Crowther M, Crowther MA. Antidotes for novel oral anticoagulants: current status and future potential. Arterioscler Thromb Vasc Biol 2015; 35 (8) 1736-1745
- 57 Hollenbach S, Lu G, DeGuzman F , et al. Abstract 14657: Andexanet-alfa and PER977 (Arapazine) Correct Blood Loss in a Rabbit Liver Laceration Model - Only Andexanet Reverses Markers of fXa-mediated Anticoagulation. Circulation 2014; 130 (Suppl. 02) A14657
- 58 Ansell JE, Bakhru SH, Laulicht BE , et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014; 371 (22) 2141-2142