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Review

Current and emerging pharmacotherapy for ischemic stroke prevention in patients with atrial fibrillation

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Pages 1999-2009 | Received 09 May 2018, Accepted 15 Oct 2018, Published online: 25 Oct 2018

References

  • Lip GYH , Freedman B , de Caterina R , et al. Stroke prevention in atrial fibrillation: past, present and future comparing the guidelines and practical decision-making. Thromb. Haemost. 2017;117:1230–1239.
  • Hart RG , Pearce LA , Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–867.
  • Gallagher AM , Setakis E , Plumb JM , et al. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb. Haemost. [Internet]. 2011;106:968–977.
  • Vestergaard AS , Skjøth F , Larsen TB , et al. The importance of mean time in therapeutic range for complication rates in warfarin therapy of patients with atrial fibrillation: A systematic review and meta-regression analysis. PLoS One. 2017;12:e0188482. doi: 10.1371/journal.pone.0188482.
  • Esteve-Pastor M , Rivera-Caravaca J , Roldán-Rabadán I , et al. Relation of renal dysfunction to quality of anticoagulation control in patients with atrial fibrillation: the fantasiia registry. Thromb. Haemost. [Internet]. 2018;118:279–287. Available from http://www.ncbi.nlm.nih.gov/pubmed/29443369%0Ahttp://www.thieme-connect.de/DOI/DOI?10.1160/TH17-06-0416
  • Lip GYH , Collet JP , De CR , et al. Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working. Europace [Internet]. 2017;19:1757–1758.
  • Mazurek M , Huisman M , Rothman K , et al. Regional differences in antithrombotic treatment for atrial fibrillation: insights from the GLORIA-AF phase II registry. Thromb. Haemost. [Internet]. 2017;117:2376–2388.
  • Senoo K , Lip GYH. Comparative efficacy and safety of the non-vitamin k antagonist oral anticoagulants for patients with nonvalvular atrial fibrillation. Semin. Thromb. Hemost. 2015;41:146–153.
  • Lip GYH , Keshishian A , Kamble S , et al. Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin. Thromb. Haemost. [Internet]. 2016;116:975–986.
  • Ruff CT , Giugliano RP , Braunwald E , et al. 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;383:955–962.
  • Alamneh EA , Chalmers L , Bereznicki LR . Suboptimal use of oral anticoagulants in atrial fibrillation: has the introduction of direct oral anticoagulants improved prescribing practices? Am. J. Cardiovasc. Drugs. 2016;183–200.
  • Steffel J , Verhamme P , Potpara TS , et al. The 2018 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur. Heart J. [Internet]. 2018;1–64. Available from https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehy136/4942493
  • Pollack CV Jr. , Pa R , Eikelboom J , et al. Idarucizumab for dabigatran reversal. N.Engl.J.Med. 2015;373:511–520.
  • Deborah M. Siegal , M.D., John , et al. Andexanet alfa for the reversal of factor xa inhibitor activity. N Engl J Med. 2015;373:2413–2424.
  • Ansell JE , Bakhru SH , Laulicht BE , et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N. Engl. J. Med. [Internet]. 2014;371:2141–2142. Available from http://www.nejm.org/doi/10.1056/NEJMc1411800
  • US Food and Drug Administration . BEVYXXA (Betrixaban) Prescribing Information. FDA [Internet]. [cited 2018 Oct 03]. 2017. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208383s001lbl.pdf.
  • Cohen AT , Harrington RA , Goldhaber SZ , et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N. Engl. J. Med. [Internet]. 2016;375:534–544. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1601747
  • Connolly SJ , Eikelboom J , Dorian P , et al. Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa). Eur. Heart J. 2013;34:1498–1505.
  • Rao PSS , Burkart T . Advances in oral anticoagulation therapy – what’s in the pipeline?. Blood Rev. 2017;31:205–211.
  • Lip GYH , Halperin JL , Petersen P , et al. A Phase II, double-blind, randomized, parallel group, dose-finding study of the safety and tolerability of darexaban compared with warfarin in patients with non-valvular atrial fibrillation (OPAL-2). J. Thromb. Haemost. [Internet]. 2015;13:1405–1413. Available from http://www.ncbi.nlm.nih.gov/pubmed/26052866
  • Goldstein S , Bates ER , Bhatt DL , et al. Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome. Thromb. Haemost. 2014;111:1141–1152.
  • Agnelli G , Haas S , Js G , et al. A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement. J. Thromb. Haemost. [Internet]. 2007;5:746–753. Available from http://www.ncbi.nlm.nih.gov/pubmed/17408408
  • Choi H , Choi S , Kim Y , et al. Population pharmacokinetic and pharmacodynamic modeling analysis of GCC-4401C, a novel direct factor xa inhibitor, in healthy volunteers. CPT Pharmacometrics Syst. Pharmacol.. 2016;5:532–543.
  • Cohen AT , Boyd RA , Mandema JW , et al. An adaptive-design dose-ranging study of PD 0348292, an oral factor Xa inhibitor, for thromboprophylaxis after total knee replacement surgery. J. Thromb. Haemost.. 2013;11:1503–1510.
  • De Caterina R , Husted S , Wallentin L , et al. Vitamin K antagonists in heart disease: current status and perspectives (section iii). position paper of the ESC working group on thrombosis–task force on anticoagulants in heart disease. Thromb. Haemost. [Internet]. 2013;110:1087–1107. Available from http://th.schattauer.de/en/contents/archive/issue/1810/manuscript/20501.html
  • Bonde AN , Lip GYH , A-L K , et al. Renal function, time in therapeutic range and outcomes in warfarin-treated atrial fibrillation patients: a retrospective analysis of nationwide registries. Thromb. Haemost. [Internet]. 2017;117:2291–2299. Available from http://www.thieme-connect.de/DOI/DOI?10.1160/TH17-03-0198%0Ahttp://www.ncbi.nlm.nih.gov/pubmed/29212117
  • Zoppellaro G , Granziera S , Bertozzo G , et al. Consequences of warfarin suspension after major bleeding in very elderly patients with non valvular atrial fibrillation. Thromb. Haemost. 2017;1828–1830.
  • Hobl EL, Jilma B. Tecarfarin: A Novel Vitamin K Antagonist. Thromb Haemost . 2017;117:2009–2011.
  • Bavisotto LM , Ellis DJ , Milner PG , et al. Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants. J. Clin. Pharmacol. 2011;51:561–574.
  • Albrecht D , Ellis D , Canafax DM , et al. Pharmacokinetics and pharmacodynamics of tecarfarin, a novel vitamin K antagonist oral anticoagulant. Thromb Haemost. 2017;117:706–717.
  • Ellis DJ , Usman MH , Milner PG , et al. The first evaluation of a novel vitamin K antagonist, tecarfarin (ATI-5923), in patients with atrial fibrillation. Circulation. 2009;120:1029–1035.
  • Whitlock RP , Fordyce CB , Midei MG , et al. A randomised, double blind comparison of tecarfarin, a novel vitamin k antagonist, with warfarin the embraceac trial. Thromb. Haemost. 2016;116:241–250.
  • Albrecht D , Turakhia MP , Ries D , et al. Pharmacokinetics of tecarfarin and warfarin in patients with severe chronic kidney disease. Thromb Haemost. 2017;117:2026–2033.
  • Camire RM , Bos MHA . The molecular basis of factor V and VIII procofactor activation. J. Thromb. Haemost. 2009;1951–1961.
  • Bos MHA , Camire RM . Blood coagulation factors V and VIII: molecular mechanisms of procofactor activation. J. Coagul. Disord. [Internet]. 2010;2:19–27. Available from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3001592&tool=pmcentrez&rendertype=abstract
  • Espana F , Medina P , Navarro S , et al. The multifunctional protein C system. Curr. Med. Chem. Cardiovasc. Hematol. Agents. 2005;3:119–131.
  • Kearon C , Comp P , Douketis J , et al. Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement. J. Thromb. Haemost. 2005;3:962–968. Internet]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15869592
  • Saito H , Maruyama I , Shimazaki S , et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost [Internet]. 2007;5:31–41. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17059423
  • Wada H , Okamoto K , Iba T , et al. Addition of recommendations for the use of recombinant human thrombomodulin to the “expert consensus for the treatment of disseminated intravascular coagulation in Japan.”. Thromb Res. 2014;134:924–925.
  • Verhamme P , Pakola S , Jensen TJ , et al. Tolerability and pharmacokinetics of TB-402 in healthy male volunteers. Clin. Ther. 2010;32:1205–1220.
  • Verhamme P , Tangelder M , Verhaeghe R , et al. Single intravenous administration of TB-402 for the prophylaxis of venous thromboembolism after total knee replacement: a dose-escalating, randomized, controlled trial. J. Thromb. Haemost. 2011;9:664–671.
  • Verhamme P , Gunn S , Sonesson E , et al. Single-dose TB-402 or rivaroxaban for the prevention of venous thromboembolism after total hip replacement: A randomised, controlled trial. Thromb. Haemost. 2013;109:1091–1098.
  • Howard EL, Becker KC, Rusconi CP, et al. Factor IXa inhibitors as novel anticoagulants. Arterioscler Thromb Vasc Biol . 2007;27:722–727.
  • Gómez-Outes A , García-Fuentes M , Suárez-Gea ML . Discovery methods of coagulation-inhibiting drugs. expert opin. Drug Discov. [Internet]. 2017;12:1195–1205. Available from.
  • Franchini M , Mannucci PM . The history of hemophilia. Semin. Thromb. Hemost. 2014;571–576.
  • Eriksson BI , Dahl OE , Lassen MR , et al. Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study. J. Thromb. Haemost. 2008;6:457–463.
  • Povsic TJ , Vavalle JP , Alexander JH , et al. Use of the REG1 anticoagulation system in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the phase II RADAR-PCI study. EuroIntervention J. Eur. Collab. With Work. Gr. Interv. Cardiol. Eur. Soc. Cardiol. 2014;10:431–438.
  • Lincoff AM , Mehran R , Povsic TJ , et al. Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): A randomised clinical trial. Lancet. 2016;387:349–356.
  • Brill A , Fuchs TA , Savchenko AS , et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J. Thromb. Haemost. 2012;10:136–144.
  • Kannemeier C , Shibamiya A , Nakazawa F , et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc. Natl. Acad. Sci. [Internet]. 2007;104:6388–6393. Available from http://www.pnas.org/cgi/doi/10.1073/pnas.0608647104
  • Gould TJ , Vu TT , Swystun LL , et al. Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms. Arterioscler. Thromb. Vasc. Biol. 2014;34:1977–1984.
  • McFadyen JD , Jackson SP . Differentiating haemostasis from thrombosis for therapeutic benefit. Thromb. Haemost. 2013;110:859–867.
  • Renné T , Pozgajová M , Grüner S , et al. Defective thrombus formation in mice lacking coagulation factor XII. J. Exp. Med. [Internet]. 2005;202:271–281. Available from http://www.jem.org/lookup/doi/10.1084/jem.20050664
  • Renné T , Oschatz C , Seifert S , et al. Factor XI deficiency in animal models. J. Thromb. Haemost. 2009;79–83.
  • Key NS . Epidemiologic and clinical data linking factors XI and XII to thrombosis. Hematology. 2014;2014:66–70.
  • Gailani D, Bane CE, Gruber A. Factor XI and contact activation as targets for antithrombotic therapy. J Thromb Haemost . 2015;13:1383–1395.
  • Renné T , Schmaier AH , Nickel KF , et al. In vivo roles of factor XII. Blood. 2012;4296–4303.
  • Van Montfoort ML , Meijers JCM . Recent insights into the role of the contact pathway in thrombo-inflammatory disorders. Hematology. 2014;2014:60–65.
  • Bickmann JK , Baglin T , Meijers JCM , et al. Novel targets for anticoagulants lacking bleeding risk. Curr Opin Hematol. 2017;24:419–426.
  • Buller HR , Bethune C , Bhanot S , et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N. Engl. J. Med. 2015;372:232–240.
  • Cheng Q , Tucker EI , Pine MS , et al. A role for factor XIIa-mediated factor XI activation in thrombus formation in vivo. Blood. 2010;116:3981–3989.
  • Tucker EI , Marzec UM , White TC , et al. Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI. Blood. 2009;113:936–944.
  • Gómez-Outes A , García-Fuentes M , Suárez-Gea ML , et al. Factors XI and XII as targets for new anticoagulants. Front. Med. [Internet]. 2017;4:147–154. Available from http://journal.frontiersin.org/article/10.3389/fmed.2017.00019/full
  • Yau JW , Liao P , Fredenburgh JC , et al. Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits. Blood. 2014;123:2102–2107.
  • Crosby JR , Marzec U , Revenko AS , et al. Antithrombotic effect of antisense factor xi oligonucleotide treatment in primates. Arterioscler. Thromb. Vasc. Biol. 2013;33:1670–1678.
  • Wong PC , Quan ML , Watson CA , et al. In vitro, antithrombotic and bleeding time studies of BMS-654457, a small-molecule, reversible and direct inhibitor of factor XIa. J. Thromb. Thrombolysis. 2015;40:416–423.
  • Wong P , Quan M , Watson C . A small-molecule and direct inhibitor of factor xia provides strong antithrombotic activity with low bleeding in non-human primate model of arterial thrombosis. Res. Pract. Thromb. Haemost. [Internet]. 2017;1:OC40.4. Available from http://www.professionalabstracts.com/isth2017/iplanner/#/presentation/678
  • Kouyama S , Ono T , Hagio T , et al. Discovery of ONO-5450598, a highly orally bioavailable small molecule factor XIa inhibitor: the pharmacokinetic and pharmacological profiles. Res. Pract. Thromb. Haemost. [Internet]. 2017;1:PB 2139. Available from https://www.postersessiononline.eu/173580348_eu/congresos/ISTH2017/aula/-PB_2139_ISTH2017.pdf
  • Revenko AS , Gao D , Crosby JR , et al. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding. Blood. 2011;118:5302–5311.
  • Larsson M , Rayzman V , Nolte MW , et al. A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. Sci Transl Med. 2014;6:222ra17.
  • Matafonov A , Leung PY , Gailani AE , et al. Factor XII inhibition reduces thrombus formation in a primate thrombosis model. Blood. 2014;123:1739–1746.
  • Woodruff RS , Xu Y , Layzer J , et al. Inhibiting the intrinsic pathway of coagulation with a factor XII-targeting RNA aptamer. J. Thromb. Haemost. 2013;11:1364–1373.
  • Siller-Matula JM , Schwameis M , Blann A , et al. Thrombin as a multi-functional enzyme: focus on in vitro and in vivo effects. Thromb Haemost. 2011;106:1020–1033.
  • Bates SM , Weitz JI . The mechanism of action of thrombin inhibitors. J. Invasive Cardiol. [Internet]. 2000;12(Suppl F):27F–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11156731
  • Albers GW , Diener HC , Grind M , et al. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet [Internet]. 2003;362:1691–1698.
  • Keisu M , Andersson TB . Drug-induced liver injury in humans: the case of ximelagatran. Handb. Exp. Pharmacol. [Internet]. 2010;196:407–418. Available from http://www.springerlink.com/index/10.1007/978-3-642-00663-0%0Ahttp://www.ncbi.nlm.nih.gov/pubmed/20020269
  • Lip GYH , Rasmussen LH , Olsson SB , et al. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur. Heart J. [Internet]. 2009;30:2897–2907. Available from https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehp318
  • Lip GYH , Rasmussen LH , Bertil Olsson S , et al. Exposure-response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation. Br. J. Clin. Pharmacol. 2015;80:1362–1373.
  • Olsson SB , Rasmussen LH , Tveit A , et al. Safety and tolerability of an immediate-release formulation of theoral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Thromb. Haemost. [Internet]. 2010;103:604–612. Available from.
  • Baglin TP , Langdown J , Frasson R , et al. Discovery and characterization of an antibody directed against exosite I of thrombin. J. Thromb. Haemost. 2016;14:137–142.
  • Lip GYH . The ABC pathway: an integrated approach to improve AF management. Nat. Rev. Cardiol. 2017;14:627–628.

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