Hemorrhagic side effects are the bane of oral anticoagulation. Despite careful selection of medications and close monitoring, some adverse events are unavoidable. The available literature about the risks of triple oral anticoagulation therapy versus dual antiplatelet therapy does not address all of the medication combinations currently available. This report describes a patient with atrial fibrillation and recent stent placement who developed severe, recurrent epistaxis on aspirin, prosugrel, and rivaroxaban. We believe this is the first case report of severe bleeding with this combination, and it may help provide insights into the risk for other patients. 1. Introduction Several options, with well-described bleeding risks, exist for the chemoprophylaxis of thrombotic complications of either atrial fibrillation or coronary stents in isolation. However, therapy is less clear when the two conditions are comorbid. The “gold standard” therapies differ for each and provide suboptimal risk reduction for the other condition. For example, the combination of aspirin and a thienopyridine inhibitor is recommended to prevent in-stent thrombosis but is inferior to warfarin or the newer oral anticoagulants for the prevention of stroke in atrial fibrillation. As a result, some clinicians have utilized both gold standard therapies simultaneously, resulting in triple oral antithrombotic therapy. While this strategy theoretically minimizes the risk of thrombotic complications, it may increase the risk of bleeding beyond the benefits gained. The net risk-benefit ratio for patients for patients on triple antithrombotic therapy should drive treatment decisions, yet it is often unclear. 2. Case A 55-year-old Caucasian male presented to the emergency department for one-day history of intractable nausea and vomiting and was found to be in atrial fibrillation with rapid ventricular response. He had a known history of paroxysmal atrial fibrillation but had previously refused warfarin therapy. His past medical history was otherwise significant for congestive heart failure preserved ejection fraction, coronary artery disease treated with a bare metal stent six months prior, diabetes mellitus type 2, hypertension, gout, and chronic kidney disease stage 3 (creatinine clearance 30). His home medications included prasugrel, aspirin atorvastatin, clonidine, furosemide, potassium chloride, amlodipine, insulin, allopurinol, and hydralazine. His nausea and vomiting were treated with supportive care and he was started on heparin and diltiazem drip for his atrial fibrillation. Cardiology
References
[1]
S. B. King III, S. C. Smith Jr., J. W. Hirshfeld Jr. et al., “2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association task force on practice guidelines,” Circulation, vol. 117, no. 2, pp. 261–295, 2008.
[2]
S. Connolly, J. Pogue, R. Hart 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,” The Lancet, vol. 367, no. 9526, pp. 1903–1912, 2006.
[3]
R. L. McNamara, L. J. Tamariz, J. B. Segal, and E. B. Bass, “Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography,” Annals of Internal Medicine, vol. 139, no. 12, pp. 1018–1033, 2003.
[4]
R. G. Hart, L. A. Pearce, and M. I. Aguilar, “Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation,” Annals of Internal Medicine, vol. 146, no. 12, pp. 857–867, 2007.
[5]
M. B. Leon, D. S. Baim, J. J. Popma et al., “A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting,” The New England Journal of Medicine, vol. 339, no. 23, pp. 1665–1671, 1998.
[6]
D. P. Faxon, J. W. Eikelboom, P. B. Berger et al., “Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: a North American perspective: executive summary,” Circulation: Cardiovascular Interventions, vol. 4, no. 5, pp. 522–534, 2011.
[7]
H.-J. Zhao, Z.-T. Zheng, Z.-H. Wang 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, vol. 139, no. 2, pp. 260–270, 2011.
[8]
M. L. Hansen, R. S？rensen, M. T. Clausen et al., “Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation,” Archives of Internal Medicine, vol. 170, no. 16, pp. 1433–1441, 2010.
[9]
R. S？rensen, M. L. Hansen, S. Z. Abildstrom et al., “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,” The Lancet, vol. 374, no. 9706, pp. 1967–1974, 2009.
[10]
J. S. Paikin, D. S. Wright, M. A. Crowther, S. R. Mehta, and J. W. Eikelboom, “Triple antithrombotic therapy in patients with atrial fibrillation and coronary artery stents,” Circulation, vol. 121, no. 18, pp. 2067–2070, 2010.
[11]
W. J. Dewilde, T. Oirbans, F. W. Verheugt, et al., “Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial,” The Lancet, vol. 381, no. 9872, pp. 1107–1115, 2013.
[12]
V. Fuster, L. E. Ryden, D. S. Cannom, et al., “ACC/AHA/ESC 2006 guidelines 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 European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society,” Circulation, vol. 114, no. 7, pp. e257–e354, 2006.
[13]
J. J. You, D. E. Singer, P. A. Howard, et al., “Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest, vol. 141, pp. e531S–e575S, 2012.
[14]
T. Y. Wang, L. A. Robinson, F.-S. Ou et al., “Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: physician practice in the CRUSADE registry,” American Heart Journal, vol. 155, no. 2, pp. 361–368, 2008.
[15]
M. R. Patel, K. W. Mahaffey, J. Garg et al., “Rivaroxaban versus warfarin in nonvalvular atrial fibrillation,” The New England Journal of Medicine, vol. 365, no. 10, pp. 883–891, 2011.
[16]
J. Mega, E. Braunwald, S. Mohanavelu et al., “Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial,” The Lancet, vol. 374, no. 9683, pp. 29–38, 2009.
[17]
J. L. Mega, E. Braunwald, S. D. Wiviott et al., “Rivaroxaban in patients with a recent acute coronary syndrome,” The New England Journal of Medicine, vol. 366, no. 1, pp. 9–19, 2012.
[18]
J. L. Mega, E. Braunwald, S. D. Wiviott et al., “Comparison of the efficacy and safety of two rivaroxaban doses in acute coronary syndrome (from ATLAS ACS 2-TIMI 51),” American Journal of Cardiology, vol. 112, no. 4, pp. 472–478, 2013.
[19]
S. D. Wiviott, D. Trenk, A. L. Frelinger et al., “Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the prasugrel in comparison to clopidogrel for inhibition of platelet activation and aggregation-thrombolysis in myocardial infarction 44 trial,” Circulation, vol. 116, no. 25, pp. 2923–2932, 2007.
[20]
S. D. Wiviott, E. Braunwald, C. H. McCabe et al., “Prasugrel versus clopidogrel in patients with acute coronary syndromes,” The New England Journal of Medicine, vol. 357, no. 20, pp. 2001–2015, 2007.
[21]
S. R. Mehta, J.-F. Tanguay, J. W. Eikelboom et al., “Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial,” The Lancet, vol. 376, no. 9748, pp. 1233–1243, 2010.
[22]
D. L. Bhatt, J. Scheiman, N. S. Abraham, et al., “ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use,” The American Journal of Gastroenterology, vol. 103, no. 11, pp. 2890–2907, 2008.
