Triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting: hovering among bleeding risk, thromboembolic events, and stent thrombosis

Thrombosis Journal

Roberto Grilli³  Rossana De Palma³  Antonio Manari²  Andrea Rubboli¹  Mila Menozzi² 

[1] Division of Cardiology & Cardiac Catheterization Laboratory, Maggiore HospitalLargo Nigrisoli, 2 – 40133, Bologna, Italy;Interventional Cardiology, S. Maria Nuova Hospital; Viale Risorgimento, 80 - 42123 Reggio Emilia, Italy;Regional Agency for Health and Social Care, Viale Aldo Moro, 21 - 40127, Bologna, Italy

关键词: Antiplatelet drugs;    Warfarin;    Stent;    Percutaneous coronary intervention;    Atrial fibrillation;   

Others  :  838829
DOI  :  10.1186/1477-9560-10-22

 received in 2012-07-31, accepted in 2012-10-09,  发布年份 2012

【 摘 要 】

Dual antiplatelet treatment with aspirin and clopidogrel is the antithrombotic treatment recommended after an acute coronary syndrome and/or coronary artery stenting. The evidence for optimal antiplatelet therapy for patients, in whom long-term treatment oral anticoagulation is mandatory, is however scarce. To evaluate the safety and efficacy of the various antithrombotic strategies adopted in this population, we reviewed the available evidence on the management of patients receiving oral anticoagulation, such as a vitamin-k-antagonists, referred for coronary artery stenting.

Atrial fibrillation is the most frequent indication for oral anticoagulation. The need of starting antiplatelet therapy in this clinical scenario raises concerns about the combination to choose: triple therapy with warfarin, aspirin, and a thienopyridine being the most frequent and advised. The safety of this regimen appeared suboptimal because of an increased risk in hemorrhagic complications. On the other hand, the combination of oral anticoagulation and an antiplatelet agent is suboptimal in preventing thromboembolic events and stent thrombosis; dual antiplatelet therapy may be considered only when a high hemorrhagic risk and low thromboembolic risk are perceived. Indeed, the need for prolonged multiple-drug antithrombotic therapy increases the bleeding risks when drug eluting stents are used.

Since current evidence derives mainly from small, single-center and retrospective studies, large-scale prospective multicenter studies are urgently needed.

【 授权许可】

   
2012 Menozzi et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Camm AJ, Kirchhof P, Lip GY, et al.: 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 2010, 31:2369-2429.
• [2]Lip GY, Huber K, Andreotti F, et al.: Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. A Consensus Document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Thromb Haemost 2010, 103:13-28.
• [3]Guyatt GH, Akl EA, Crowther M, et al.: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012, 141(2)(Suppl):7S-74S.
• [4]Wijns W, Kolh P, Danchin N, et al.: Guidelines on myocardial revascularization. Eur Heart J 2010, 31:2501-2555.
• [5]Rubboli A, Colletta M, Valencia J, et al.: Periprocedural Management and In-Hospital Outcome of Patients with Indication for Oral Anticoagulation Undergoing Coronary Artery Stenting. J Interven Cardiol 2009, 22:390-397.
• [6]Connolly S, Pogue J, Hart R, ACTIVE Writing Group of the ACTIVE Investigators, et al.: Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006, 367:1903-1912.
• [7]Rubboli A, Milandri M, Castelvetri C, Cosmi B: Meta-analysis of trials comparing oral anticoagulation and aspirin versus dual antiplatelet therapy after coronary stenting. Clues for the management of patients with an indication for long-term anticoagulation undergoing coronary stenting. Cardiology 2005, 104:101-106.
• [8]Rubboli A, Dewilde W, Huber K, et al.: The Management of Patients on Oral Anticoagulation Undergoing Coronary Stent Implantation: A Survey among Interventional Cardiologists from Eight European Countries. J Interv Cardiol 2012, 25(2):163-169.
• [9]Orford JL, Fasseas P, Melby S, et al.: Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J 2004, 147:463-467.
• [10]Mattichack SJ, Reed PS, Gallagher MJ, et al.: Evaluation of safety of warfarin in combination with antiplatelet therapy for patients treated with coronary stents for acute myocardial infarction. J Interven Cardiol 2005, 18:163-166.
• [11]Khurram Z, Chou E, Minutello R, et al.: Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol 2006, 18(4):162-164.
• [12]Porter A, Konstantino Y, Iakobishvili Z, et al.: Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 2006, 68:56-61.
• [13]Lip GYH, Karpha M: Anticoagulant and antiplatelet therapy use in patients with atrial fibrillation undergoing percutaneous coronary intervention: the need for consensus and a management guideline. Chest 2006, 130:1823-1827.
• [14]Karjalainen PP, Porela P, Ylitalo A, et al.: Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J 2007, 28:726-732.
• [15]DeEugenio D, Kolman L, DeCaro M, et al.: Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy. Pharmacoherapy 2007, 27(5):691-696.
• [16]Rubboli A, Colletta M, Herzfeld J, Sangiorgio P, Di Pasquale G: Peri-procedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention. Coron Artery Dis 2007, 18:193-199.
• [17]Nguyen MC, Lim YL, Walton A, et al.: Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent? Eur Heart J 2007, 28:1717-1722.
• [18]Rogacka R, Chieffo A, Michev I, et al.: Dual antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients taking chronic oralanticoagulation. JACC Cardiovasc Interv 2008, 1(1):56-61.
• [19]Ruiz-Nodar JM, Marin F, Hurtado JA, et al.: Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention andstent implantation implications for bleeding riskandprognosis. J Am Coll Cardiol 2008, 51(8):818-825.
• [20]Manzano-Fernandez S, Pastor FJ, Marin F, et al.: Increased major bleeding complications related to triple antithrombotic therapy usage in patients with atrial fibrillation undergoing percutaneous coronary artery stenting. Chest 2008, 134(3):559-567.
• [21]Sarafoff N, Ndrepepa G, Mehilli J, et al.: Aspirin and clopidogrelwith or without phenprocoumon after drug eluting coronary stentplacement in patients on chronic oral anticoagulation. J Intern Med 2008, 264:472-480.
• [22]Maegdefessel L, Schlitt A, Faerber J, et al.: Anticoagulant and/or antiplatelet treatment in patients with atrial fibrillation after percutaneous coronary intervention. A single-center experience. Med Klin (Munich) 2008, 103(9):628-632.
• [23]Rossini R, Musumeci G, Lettieri C, et al.: Outcomes of long-term triple therapy with aspirin, clopidogrel, and warfarin in patientsundergoing coronary stenting [abstract]. Eur Heart 2008, 29(Suppl):328.
• [24]Valencia J, Mainar V, Bordes P, et al.: Observance of Antiplatelet Therapy after Stent Implantation in Patients under Chronic Oral Anticoagulant Treatment. J Interven Cardiol 2008, 21:218-224.
• [25]Gao F, Zhou YJ, Wang ZJ, et al.: Comparison of Different Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Drug-Eluting Stent Implantation. Circ J 2010, 74:701-708.
• [26]Sambola A, Ferreira-González I, Angel J, et al.: Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study. Heart 2009, 95(18):1483-1488.
• [27]Gilard M, Blanchard D, Helft G, et al.: Antiplatelet therapy in patients with anticoagulants undergoing percutaneous coronary stenting (from STENTIng and oral antiCOagulants [STENTICO]). Am J Cardiol 2009, 104(3):338-342.
• [28]Hälg C, Brunner-La Rocca HP, Kaiser C, et al.: Early and late increased bleeding rates after angioplasty and stenting due to combined antiplatelet and anticoaglant therapy. EuroIntervention 2009, 5:425-431.
• [29]Halbfass P, Janko S, Dorwarth U, et al.: Dilemma of antithrombotic therapy in anticoagulated atrial fibrillation patients squeezed between thrombosis and bleeding events: a single-center experience. Europace 2009, 11:957-960.
• [30]Helft G, Dambrin G, Zaman A, et al.: Percutaneous coronary intervention in anticoagulated patients via radial artery access. Catheter Cardiovasc Interv 2009, 73:44-47.
• [31]Olson KL, Delate T, Johnson SG, et al.: Incidence of hemorrhage among anticoagulated patients receiving antiplatelet therapy after percutaneous coronary intervention. J Thromb Thrombolysis 2009, 29:316-321.
• [32]Baber U, Akhter M, Kothari S, et al.: Efficacy of modified dual antiplatelet therapy combined with warfarin following percutaneous coronary intervention with drug-eluting stents. J Invasive Cardiol 2010, 22:80-83.
• [33]Persson J, Lindbaeck J, Hofman-Bang C, et al.: Efficacy and safety of clopidogrel after PCI with stenting in patients on oral anticoagulants with acute coronary syndrome. EuroIntervention 2011, 6:1046-1052.
• [34]Uchida Y, Mori F, Ogawa H, et al.: Impact of anticoagulant therapy with dual antiplatelet therapy on prognosis after treatment with drug-eluting coronary stents. J Cardiol 2010, 55:362-369.
• [35]Guasch E, Sionis A, Reverter JC, et al.: Safety issues of adjunctive clopidogrel in patients discharged after percutaneous coronary intervention with stent placement and requiring oral anticoagulation. Int J Cardiol 2011, 146:e1-e4.
• [36]Jang S-W, Rho T-H, Kim D-B, et al.: Optimal antithrombotic strategy in patients with atrial fibrillation after coronary stent implantation. Korean Circ J 2011, 41:578-582.
• [37]Zhao H-J, Zheng Z-T, Wang Z-H, et al.: “Triple Therapy” Rather Than “Triple Threat” A Meta-analysis of the Two Antithrombotic Regimens After Stent Implantation in Patients Receiving Long-term Oral Anticoagulant Treatment. Chest 2011, 139(2):260-270.
• [38]Rubboli A, Halperin JL: Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regime in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions. Thromb Haemost 2008, 100(5):752-753.
• [39]Faxon DP, Eikelboom JW, Berger PB, et al.: Consensus Document: Antithrombotic therapy in patients with atriale fibrillation undergoing coronary stenting. Thromb Haemost 2011, 106:571-584.
• [40]Rubboli A, Magnavacchi P, Guastaroba P, et al.: Antithrombotic Management and 1-Year Outcome of Patients on Oral Anticoagulation Undergoing Coronary Stent Implantation (from the Registro Regionale Angioplastiche Emilia-Romagna Registry). Am J Cardiol 2012, 109:1411-1417.
• [41]Beyth RJ, Quinn LM, Landefeld CS: Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998, 105:91-99.
• [42]Shiotani A, Manabe N, Kamada T, et al.: Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: A comprehensive review. J Gastroenterol Hepatol 2012, 27(Suppl. 3):8-12.
• [43]Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ: Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest 2010, 137:263-272.
• [44]Agostoni P, Biondi-Zoccai GGL, De Benedictis L, et al.: Radial versus femoral approach for percutaneous coronary diagnostic and interventional procedures: systematic overview and meta-analysis of randomized trials. J Am Coll Cardiol 2004, 44:349-356.
• [45]Ziakas AG, Koskinas KC, Gavrilidis S, et al.: Radial versus femoral access for orally anticoagulated patients. Catheter Cardiovasc Interv 2010, 76:493-499.
• [46]Jessup DB, Coletti AT, Muhlestein JB, et al.: Elective coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy. Catheter Cardiovasc Interv 2003, 60:180-184.
• [47]Karjalainen P, Porela P, Ylitalo A, et al.: Safety of percutaneous coronary intervention during uninterrupted anticoagulation treatment. Int J Cardiol 2007, 119:9. abstr
• [48]Lahtela H, Rubboli A, Schlitt A, et al.: Heparin Bridging vs. Uninterrupted Oral Anticoagulation in Patients With Atrial Fibrillation Undergoing Coronary Artery Stenting. Circ J 2012, 76(6):1363-1368.
• [49]Bonello L, Armero S, Sbragia P, Paganelli F, Ait Mokhtar O: Early and late outcomes of clopidogrel and Coumadin combination for patients on oral anticoagulants undergoing coronary stenting. Cardiovasc Revasc Med 2010, 11:159-162.
• [50]Lip G, Frison L, Halperin JL, Lane DA: Comparative Validation of a Novel Risk Score for Predicting Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation. J Am Coll Cardiol 2011, 57:173-180.
• [51]Cantor WJ, Peterson ED, Popma JJ, et al.: Provisional stenting strategies: systematic overview and implication for clinical decision-making. J Am Coll Cardiol 2000, 36:1142-1151.
• [52]Rubboli A, Kovacic JC, Mehran R, Lip GY: Coronary stent implantation in patients committed to long-term oral anticoagulation therapy: successfully navigating the treatment options. Chest 2011, 139(5):981-987.
• [53]Serruys PW, Silber S, Garg S, et al.: Comparison of Zotarolimus-Eluting and Everolimus-Eluting Coronary Stents. N Engl J Med 2010, 363:136-146.
• [54]Connolly SJ, Ezekowitz MD, Yusuf S, et al.: Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009, 361:1139-1151.
• [55]Connolly SJ, Eikelboom J, Joyne C, et al.: Apixaban in Patients with Atrial Fibrillation. N Engl J Med 2011, 364:806-817.
• [56]Patel MR, Mahaffey KW, Garg J, et al.: Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med 2011, 365:883-891.
• [57]Mega JL, Braunwald E, Wiviott SD, et al.: Rivaroxaban in Patients with a Recent Acute Coronary Sindrome. N Engl J Med 2012, 366:9-19.
• [58]Alexander JH, Lopes RD, James S, et al.: Apixaban with Antiplatelet therapy after Acute Coronary Syndrome. N Engl J Med 2011, 365:699-708.
• [59]Wiviott SD, Braunwald E, McCabe CH, et al.: Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2007, 57:2001-2015.
• [60]Wallentin L, Becker RC, Budaj A, et al.: Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2009, 361:1045-1057.
• [61]Hahn J-Y, Song YB, Choi J-H, et al.: Three-month dual antiplatelet therapy after implantation of zotarolimus-eluting stents: the DATE (Duration of Dual Antiplatelet Therapy AfterImplantation of Endeavor Stent) registry. Circ J 2010, 74:2314-2321.
• [62]Stefanini GG, Kalesan B, Serruys PW, et al.: Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet 2011, 378:1940-1948.
• [63]Serruys PW, Ormiston J, Onuma Y, et al.: Absorb trial first-in-man evaluation of a bioabsorbable everolimus-eluting coronary stent system: two-year outcomes and results from multiple imaging modalities. Lancet 2009, 373:897-910.