Atrial Fibrillation and Coronary Artery Disease: Deciding on The Best Antithrombotic Regimen

Main Article Content

Jason Andrade
Laurent Macle
Marc Dyall

Keywords

Atrial fibrillation, Anticoagulation, Stroke, Coronary artery disease, Acute Coronary Syndorme, Clopidogrel, ASA, Warfarin, NOAC, Dabigatran, Rivaroxaban, Edoxaban, Apixaban

Abstract

Atrial fibrillation (AF) is a chronic progressive disease characterized by exacerbations and remissions. Up to 20-30% of patients with AF also have coronary artery disease (CAD). In patients with concomitant AF and CAD, the management of antithrombotic therapy is challenging. Oral anticoagulation (OAC) is indicated for the prevention of AF-related stroke and systemic embolism, whereas antiplatelet therapy is indicated for the prevention of coronary events. Each of these therapeutic avenues offers a relative efficacy benefit (e.g. dual antiplatelet therapy [DAPT] is more effective than OAC alone in reducing cardiovascular death, myocardial infarction, stent thrombosis, and ischemic coronary events in an ACS population), but with a relative compromise (e.g. DAPT is significantly inferior to OAC for the prevention of stroke/systemic embolism in an AF population at increased risk of AF-related stroke). The purpose of this review is to explore the current evidence and rationale for antithrombotic treatment strategies in patients with both AF and CAD.

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References

1. Feinberg WM, Blackshear JL, Laupacis A, Kronmal R and Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995;155:469-73.
2. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV and Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370-5.
3. Lip GY, Laroche C, Dan GA, Santini M, Kalarus Z, Rasmussen LH, Oliveira MM, Mairesse G, Crijns HJ, Simantirakis E, Atar D, Kirchhof P, Vardas P, Tavazzi L and Maggioni AP. A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry. Europace. 2014;16:308-19.
4. Kralev S, Schneider K, Lang S, Suselbeck T and Borggrefe M. Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography. PLoS One. 2011;6:e24964.
5. Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S and Yusuf S. 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;367:1903-12.
6. Antithrombotic Trialists C, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC and Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-60.
7. Hart RG, Pearce LA and Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857-67.
8. Group EPSIMR. A controlled comparison of aspirin and oral anticoagulants in prevention of death after myocardial infarction. N Engl J Med. 1982;307:701-8.
9. Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Coumadin Aspirin Reinfarction Study (CARS) Investigators. Lancet. 1997;350:389-96.
10. Fiore LD, Ezekowitz MD, Brophy MT, Lu D, Sacco J, Peduzzi P, Combination H and Mortality Prevention Study G. Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation. 2002;105:557-63.
11. Herlitz J, Holm J, Peterson M, Karlson BW, Haglid Evander M, Erhardt L and Lo Wsg. Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study. Eur Heart J. 2004;25:232-9.
12. Brouwer MA, van den Bergh PJ, Aengevaeren WR, Veen G, Luijten HE, Hertzberger DP, van Boven AJ, Vromans RP, Uijen GJ and Verheugt FW. Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial. Circulation. 2002;106:659-65.
13. Hurlen M, Abdelnoor M, Smith P, Erikssen J and Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347:969-74.
14. van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE and Antithrombotics in the Secondary Preventionof Events in Coronary Thrombosis-2 Research G. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet. 2002;360:109-13.
15. Andreotti F, Testa L, Biondi-Zoccai GG and Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J. 2006;27:519-26.
16. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O'Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, Stork S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S and Investigators C. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377:1319-1330.
17. Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS, Committee P-TS and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-800.
18. Udell JA, Bonaca MP, Collet JP, Lincoff AM, Kereiakes DJ, Costa F, Lee CW, Mauri L, Valgimigli M, Park SJ, Montalescot G, Sabatine MS, Braunwald E and Bhatt DL. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J. 2016;37:390-9.
19. Hess CN, Peterson ED, Peng SA, de Lemos JA, Fosbol EL, Thomas L, Bhatt DL, Saucedo JF and Wang TY. Use and Outcomes of Triple Therapy Among Older Patients With Acute Myocardial Infarction and Atrial Fibrillation. J Am Coll Cardiol. 2015;66:616-27.
20. Hansen ML, Sorensen R, Clausen MT, Fog-Petersen ML, Raunso J, Gadsboll N, Gislason GH, Folke F, Andersen SS, Schramm TK, Abildstrom SZ, Poulsen HE, Kober L and Torp-Pedersen C. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170:1433-41.
21. Fiedler KA, Maeng M, Mehilli J, Schulz-Schupke S, Byrne RA, Sibbing D, Hoppmann P, Schneider S, Fusaro M, Ott I, Kristensen SD, Ibrahim T, Massberg S, Schunkert H, Laugwitz KL, Kastrati A and Sarafoff N. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65:1619-1629.
22. Dewilde W and Berg JT. Design and rationale of the WOEST trial: What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing (WOEST). Am Heart J. 2009;158:713-8.
23. Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, Adriaenssens T, Vrolix M, Heestermans AA, Vis MM, Tijsen JG, van 't Hof AW, ten Berg JM and investigators Ws. 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. 2013;381:1107-15.
24. Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED and Fox KA. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016;375:2423-2434.
25. Gibson CM, Pinto DS, Chi G, Arbetter D, Yee M, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Burton P, van Eickels M, Korjian S, Daaboul Y, Jain P, Lip GY, Cohen M, Peterson ED and Fox KA. 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. 2017;135:323-333.
26. Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH, Committee R-DPS and Investigators. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017;377:1513-1524.
27. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T and Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383:955-62.
28. Dans AL, Connolly SJ, Wallentin L, Yang S, Nakamya J, Brueckmann M, Ezekowitz M, Oldgren J, Eikelboom JW, Reilly PA and Yusuf S. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013;127:634-40.
29. Shah R, Hellkamp A, Lokhnygina Y, Becker RC, Berkowitz SD, Breithardt G, Hacke W, Halperin JL, Hankey GJ, Fox KA, Nessel CC, Mahaffey KW, Piccini JP, Singer DE, Patel MR and Investigators RASC. Use of concomitant aspirin in patients with atrial fibrillation: Findings from the ROCKET AF trial. Am Heart J. 2016;179:77-86.
30. Alexander JH, Lopes RD, Thomas L, Alings M, Atar D, Aylward P, Goto S, Hanna M, Huber K, Husted S, Lewis BS, McMurray JJ, Pais P, Pouleur H, Steg PG, Verheugt FW, Wojdyla DM, Granger CB and Wallentin L. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2014;35:224-32.
31. Xu H, Ruff CT, Giugliano RP, Murphy SA, Nordio F, Patel I, Shi M, Mercuri M, Antman EM and Braunwald E. Concomitant Use of Single Antiplatelet Therapy With Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF-TIMI48 Trial. Journal of the American Heart Association. 2016;5.
32. Shah R, Rashid A, Hwang I, Fan TM, Khouzam RN and Reed GL. Meta-Analysis of the Relative Efficacy and Safety of Oral P2Y12 Inhibitors in Patients With Acute Coronary Syndrome. Am J Cardiol. 2017;119:1723-1728.
33. Mehta SR, Bainey KR, Cantor WJ, Lordkipanidze M, Marquis-Gravel G, Robinson SD, Sibbald M, So DY, Wong GC, Abunassar JG, Ackman ML, Bell AD, Cartier R, Douketis JD, Lawler PR, McMurtry MS, Udell JA, van Diepen S, Verma S, Mancini GBJ, Cairns JA, Tanguay JF and members of the Secondary P. 2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy. Can J Cardiol. 2018;34:214-233.
34. Sarafoff N, Martischnig A, Wealer J, Mayer K, Mehilli J, Sibbing D and Kastrati A. Triple therapy with aspirin, prasugrel, and vitamin K antagonists in patients with drug-eluting stent implantation and an indication for oral anticoagulation. J Am Coll Cardiol. 2013;61:2060-6.
35. Capodanno D, Gargiulo G, Buccheri S, Giacoppo D, Capranzano P and Tamburino C. Meta-Analyses of Dual Antiplatelet Therapy Following Drug-Eluting Stent Implantation: Do Bleeding and Stent Thrombosis Weigh Similar on Mortality? J Am Coll Cardiol. 2015;66:1639-1640.
36. Eriksson P. Long-term clopidogrel therapy after percutaneous coronary intervention in PCI-CURE and CREDO: the "Emperor's New Clothes" revisited. Eur Heart J. 2004;25:720-2.
37. Hahn JY, Song YB, Oh JH, Cho DK, Lee JB, Doh JH, Kim SH, Jeong JO, Bae JH, Kim BO, Cho JH, Suh IW, Kim DI, Park HK, Park JS, Choi WG, Lee WS, Kim J, Choi KH, Park TK, Lee JM, Yang JH, Choi JH, Choi SH, Gwon HC and investigators S-D. 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial. Lancet. 2018;391:1274-1284.
38. Palmerini T, Della Riva D, Benedetto U, Bacchi Reggiani L, Feres F, Abizaid A, Gilard M, Morice MC, Valgimigli M, Hong MK, Kim BK, Jang Y, Kim HS, Park KW, Colombo A, Chieffo A, Sangiorgi D, Biondi-Zoccai G, Genereux P, Angelini GD, Pufulete M, White J, Bhatt DL and Stone GW. Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients. Eur Heart J. 2017;38:1034-1043.
39. Mega JL, Braunwald E, Mohanavelu S, Burton P, Poulter R, Misselwitz F, Hricak V, Barnathan ES, Bordes P, Witkowski A, Markov V, Oppenheimer L and Gibson CM. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet. 2009;374:29-38.
40. Macle L, Cairns J, Leblanc K, Tsang T, Skanes A, Cox JL, Healey JS, Bell A, Pilote L, Andrade JG, Mitchell LB, Atzema C, Gladstone D, Sharma M, Verma S, Connolly S, Dorian P, Parkash R, Talajic M, Nattel S, Verma A and Committee CCSAFG. 2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation. Can J Cardiol. 2016;32:1170-1185.
41. Andrade JG, Macle L, Nattel S, Verma A and Cairns J. Contemporary Atrial Fibrillation Management: A Comparison of the Current AHA/ACC/HRS, CCS, and ESC Guidelines. Can J Cardiol. 2017;33:965-976.
42. Angiolillo DJ, Goodman SG, Bhatt DL, Eikelboom JW, Price MJ, Moliterno DJ, Cannon CP, Tanguay JF, Granger CB, Mauri L, Holmes DR, Gibson CM and Faxon DP. Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A North American Perspective-2016 Update. Circ Cardiovasc Interv. 2016;9.
43. Costa F, Tijssen JG, Ariotti S, Giatti S, Moscarella E, Guastaroba P, De Palma R, Ando G, Oreto G, Zijlstra F and Valgimigli M. Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy. Journal of the American Heart Association. 2015;4.
44. Baber U, Mehran R, Giustino G, Cohen DJ, Henry TD, Sartori S, Ariti C, Litherland C, Dangas G, Gibson CM, Krucoff MW, Moliterno DJ, Kirtane AJ, Stone GW, Colombo A, Chieffo A, Kini AS, Witzenbichler B, Weisz G, Steg PG and Pocock S. Coronary Thrombosis and Major Bleeding After PCI With Drug-Eluting Stents: Risk Scores From PARIS. J Am Coll Cardiol. 2016;67:2224-34.
45. Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, Pilgrim T, Hong MK, Kim HS, Colombo A, Steg PG, Zanchin T, Palmerini T, Wallentin L, Bhatt DL, Stone GW, Windecker S, Steyerberg EW, Valgimigli M and Investigators P-DS. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017;389:1025-1034.
46. Pasea L, Chung SC, Pujades-Rodriguez M, Moayyeri A, Denaxas S, Fox KAA, Wallentin L, Pocock SJ, Timmis A, Banerjee A, Patel R and Hemingway H. Personalising the decision for prolonged dual antiplatelet therapy: development, validation and potential impact of prognostic models for cardiovascular events and bleeding in myocardial infarction survivors. Eur Heart J. 2017;38:1048-1055.