Abstract
Anticoagulant therapy and antiplatelet therapy are used regularly for prevention of arterial and venous thrombosis, and combinations of the two drug classes are seen with relative frequency in clinical practice. While co-prescribing is as high as 39–55% in some real-world cohort studies, the number of patients that meet criteria for combination therapy based on the overall body of evidence is likely much lower. This may not always be realized by prescribers, and many patients may be continued on long term combination therapies that provide little additional benefit, and carry significant risk for harm. Given the heightened bleeding risk with combination therapies, prescribers should readily reassess the risk: benefit ratio in all patients on combination therapies. Combined antiplatelet and anticoagulant therapy should be used only in those with a low risk of bleeding who have a higher risk of thromboembolic disease events. Most patients with coronary artery disease, atrial fibrillation, peripheral arterial disease, or bioprosthetic cardiac valves will not benefit from combining antiplatelet and anticoagulant therapies. Conversely, patient populations more likely to derive benefit from antiplatelet-anticoagulant combinations include those with mechanical cardiac valves, patients undergoing percutaneous cardiac intervention who have another indication for anticoagulant therapy, and patients with recurrent thrombotic events while being treated with a single agent. This article will attempt to provide readers with a framework to assess which patient populations are likely to derive the greatest benefit with combination anticoagulant-antiplatelet therapies relative to the weighted risk for bleeding.
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References
Hira RS, Kennedy K, Nambi V et al (2015) Frequency and practice-level variation in inappropriate aspirin use for the primary prevention of cardiovascular disease: insights from the National Cardiovascular Disease Registry’s Practice Innovation and Clinical Excellence registry. J Am Coll Cardiol 65(2):111–121
Barnes GD, Lucas E, Alexander GC, Goldberger ZD (2015) National trends in ambulatory oral anticoagulant use. Am J Med 128(12):1300-5.e2
Mackman N (2008) Triggers, targets and treatments for thrombosis. Nature 451(7181):914–918
De Caterina R, Ammentorp B, Darius H et al (2014) Frequent and possibly inappropriate use of combination therapy with an oral anticoagulant and antiplatelet agents in patients with atrial fibrillation in Europe. Heart 100:1625–1635
Bauersachs R, Berkowitz SD, Brenner B et al (2010) Rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510
Büller HR, Prins MH, Lensin AW et al (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366(14):1287–1297
Agnelli A, Buller HR, Cohen A et al (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369(9):799–808
Connolly SJ, EZekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151
Patel MR, Mahaffery KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891
Granger CB, Alexander JH, McMurray JJV et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992
Barra ME, Fanikos J, Connors JM et al (2016) Evaluation of dose-reduced direct oral anticoagulant therapy. Am J Med 129(11):1198–1204
Johnson SG, Rogers K, Delate T, Witt DM (2008) Outcomes associated with combined antiplatelet and anticoagulant therapy. Chest 133(4):948–954
Steinberg BA, Kim S, Piccini JP et al (2013) Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry. Circulation 128(7):721–728
So CH, Eckman MH (2017) Combined aspirin and anticoagulant therapy in patients with atrial fibrillation. J Thromb Thrombolysis 43(1):7–17
Dentali F, Douketis JD, Lim W, Crowther M (2007) Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Arch Intern Med 167(2):117–124
Sorensen R, Hansen ML, Abildstrom SZ et al (2009) Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet 374(9706):1967–1974
Camm AJ, Kirchhof P, Lip GY et al (2010) Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 31(19):2369–2429
Mohr JP, Thompson JLP, Lazar RM et al (2001) A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 345(20):1444–1451
Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H (2002) Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 347(13):969–974
Anand S, Yusuf S, Xie C et al (2007) Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 357(3):217–227
Ruff CT, Giugliano RP, Braunwald E et al (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383(9921):955–962
Artang R, Rome E, Nielsen JD, Vidaillet HF (2013) Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors. Am J Cardiol 112(12):1973–1979
Witt DM, Clark NP, Kaatz S, Schnurr T, Ansell JE (2016) Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis 41:187–205
Kearon C, Akl EA, Ornelas J et al (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest (149(2):315–352
Alexander JH, Lopes RD, Thomas L et al (2014) Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 35(4):224–232
Shah R, Hellkamp A, Lokhnygina Y et al (2016) Use of concomitant aspirin in patients with atrial fibrillation: findings from the ROCKET AF trial. Am Heart J 179:77–86
Oldgren J, Wallentin L, Alexander JH et al (2013) New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis. Eur Heart J 34(22):1670–1680
Xu H, Ruff CT, Giugliano RP et al (2016) Concomitant use of single antiplatelet therapy with edoxaban or warfarin in patients with atrial fibrillation: analysis from the ENGAGE AF-TIMI48 Trial. J Am Heart Assoc. https://doi.org/10.1161/JAHA.115.002587
Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. (2012) Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e576S–e600S
Colli A, Mestres CA, Castella M, Gherli T (2007) Comparing warfarin to aspirin (WoA) after aortic valve replacement with the St. Jude Medical Epic heart valve bioprosthesis: results of the WoA Epic pilot trial. J Heart Valve Dis 16(6):667–671
Aramendi JI, Mestres CA, Martinez-Leon J et al (2005) Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement: prospective, randomized, co-operative trial. Eur J Cardiotherac Surg 27(5):854–860
Heras M, Chesebro JH, Fuster V et al (1995) High risk of thrombemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol 25(5):1111–1119
Baigent C, Sudlow C, Collins R (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324(7329):71–86
Alonso-Coello P, Bellmunt S, McGorrian C et al. (2012) Antithrombotic therapy in peripheral artery disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e669S–e690s
Johnson WC, Williford WO, Corson JD, Padberg FT Jr (2004) Hemorrhagic complications during long-term postoperative warfarin administration in patients undergoing lower extremity arterial bypass surgery. Vascular 12(6):362–368
Camm AJ, Lip GY, De Caterina R et al (2012) 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 33(21):2719–2747
van Es RF, Jonker JJ, Verheugt FW et al (2002) Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 360(9327):109–113
Andreotti F, Testa L, Biondi-Zoccai CG, Crea F (2006) Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J 27(5):519–526
Testa L, Zoccai GB, Porto I et al (2007) Adjusted indirect meta-analysis of aspirin plus warfarin at international normalized ratios 2 to 3 versus aspirin plus clopidogrel after acute coronary syndromes. Am J Cardiol 99(12):1637–1642
Carreras ET, Mega JL (2013) Balancing antiplatelet and anticoagulant therapies in patients with cardiovascular disease. Cardiol Ther 2(1):85–96
Eikelboom JW, Connolly SJ, Bosch J et al (2017) Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 377(14):1319–1330
Valgimigli M, Beuno H, Byrne RA et al (2017) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. https://doi.org/10.1093/eurheartj/ehx419.
Dewilde WJ, Oirbans T, Verheugt FW et al (2013) Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 381(9872):1107–1115
Gibson CM, Mehran R, Bode C et al (2016) Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 375(25):2423–2434
Cannon CP, Bhatt DL, Oldgren J et al (2017) Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 377(16):1513–1524
January CT, Wann LS, Alpert JS et al (2014) 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 130(23):e199–e267
Gibson CM, Pinto DS, Chi G et al (2017) recurrent hospitalization among patients with atrial fibrillation undergoing intracoronary stenting treated with 2 treatment strategies of rivaroxaban or a dose-adjusted oral vitamin K antagonist treatment strategy. Circulation 135(4):323–333
Levine GN, Bates ER, Bittl JA et al (2016) 2016 ACC/AHA Guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol 68(10):1116–1139
Conway SE, Hwang AY, Ponte CD, Gums JG (2017) Laboratory and clinical monitoring of direct acting oral anticoagulants: what clinicians need to know. Pharmacotherapy 37(2):236–248
Donadini MP, Douketis JD (2010) Combine warfarin-aspirin therapy: what is the evidence? J Thromb Thrombolysis 29(2):208–213
Kernan WN, Ovbiagele B, Black HR et al (2014) Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:2160–2236
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Vandiver, J.W., Diane Beavers, K. Combining oral anticoagulation and antiplatelet therapies: appropriate patient selection. J Thromb Thrombolysis 45, 423–431 (2018). https://doi.org/10.1007/s11239-018-1635-0
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DOI: https://doi.org/10.1007/s11239-018-1635-0