{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:38:48Z","timestamp":1776087528902,"version":"3.50.1"},"reference-count":89,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,2,27]],"date-time":"2016-02-27T00:00:00Z","timestamp":1456531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue injury, coagulation and platelet response, so the treatment of ACS is based on the combined use of both antiplatelet (such as aspirin, clopidogrel, prasugrel and ticagrelor) and antithrombotic drugs (unfractionated heparin, enoxaparin, fondaparinux and bivalirudin). Bivalirudin competitively inhibits thrombin with high affinity, a predictable response from its linear pharmacokinetics and short action. However, a present remarkable controversy exists between the latest main Guidelines in Clinical Practice and the key trials evaluating the use of bivalirudin in ACS. The aim of this review is to update the development of bivalirudin, including pharmacological properties, obtained information from clinical trials evaluating efficacy and safety of bivalirudin in ACS; as well as the recommendations of clinical Guidelines.<\/jats:p>","DOI":"10.3390\/molecules21030284","type":"journal-article","created":{"date-parts":[[2016,2,29]],"date-time":"2016-02-29T10:55:59Z","timestamp":1456743359000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New Approaches to the Role of Thrombin in Acute Coronary Syndromes: Quo Vadis Bivalirudin, a Direct Thrombin Inhibitor?"],"prefix":"10.3390","volume":"21","author":[{"given":"Mar\u00eda","family":"Esteve-Pastor","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, Instituto Murciano de Investigaci\u00f3n Biosanitaria, IMIB-Arrixaca, Murcia 30120, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Hern\u00e1ndez-Romero","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, Instituto Murciano de Investigaci\u00f3n Biosanitaria, IMIB-Arrixaca, Murcia 30120, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariano","family":"Vald\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, Instituto Murciano de Investigaci\u00f3n Biosanitaria, IMIB-Arrixaca, Murcia 30120, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, Instituto Murciano de Investigaci\u00f3n Biosanitaria, IMIB-Arrixaca, Murcia 30120, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1160\/TH14-09-0765","article-title":"Bivalirudin for acute coronary syndromes: Premises, promises and doubts","volume":"113","author":"Capodanno","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1160\/TH14-02-0119","article-title":"Ticagrelor vs. prasugrel one-month maintenance therapy: Impact on platelet reactivity and bleeding events","volume":"112","author":"Alexopoulos","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.thromres.2015.05.025","article-title":"Risk and benefit of direct oral anticoagulants or PAR-1 antagonists in addition to antiplatelet therapy in patients with acute coronary syndrome","volume":"136","author":"Gao","year":"2015","journal-title":"Thromb. Res."},{"key":"ref_4","first-page":"269","article-title":"Plaque rupture, thrombosis, and therapeutic implications","volume":"26","author":"Fuster","year":"1996","journal-title":"Haemostasis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11046","DOI":"10.3390\/molecules200611046","article-title":"Development of Orally Active Thrombin Inhibitors for the Treatment of Thrombotic Disorder Diseases","volume":"20","author":"He","year":"2015","journal-title":"Molecules"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/med.20016","article-title":"Progress in the design of low molecular weight thrombin inhibitors","volume":"25","author":"Srivastava","year":"2005","journal-title":"Med. Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1046\/j.1538-7836.2003.00298.x","article-title":"What is all that thrombin for?","volume":"1","author":"Mann","year":"2003","journal-title":"J. Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1538-7836.2007.02473.x","article-title":"Factor Xa or thrombin: Is factor Xa a better target?","volume":"5","author":"Ansell","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.ahj.2014.06.014","article-title":"Antiplatelet and anticoagulation agents in acute coronary syndromes: What is the current status and what does the future hold?","volume":"168","author":"Huber","year":"2014","journal-title":"Am. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0140-6736(14)61216-2","article-title":"Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials","volume":"384","author":"Cavender","year":"2014","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.1002\/anie.201004575","article-title":"Oral, direct thrombin and factor Xa inhibitors: the replacement for warfarin, leeches, and pig intestines?","volume":"50","author":"Straub","year":"2011","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/ccd.25955","article-title":"Bivalirudin versus heparin in patients with acute myocardial infarction: A meta-analysis of randomized trials","volume":"86","author":"Ferrante","year":"2015","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/157340312803217193","article-title":"Antiplatelet and antithrombin strategies in acute coronary syndrome: State-of-the-art review","volume":"8","author":"Showkathali","year":"2012","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature06797","article-title":"Triggers, targets and treatments for thrombosis","volume":"451","author":"Mackman","year":"2008","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1056\/NEJM199201233260406","article-title":"The pathogenesis of coronary artery disease and the acute coronary syndromes. Part I","volume":"326","author":"Fuster","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1056\/NEJM199201303260506","article-title":"The pathogenesis of coronary artery disease and the acute coronary syndromes. Part II","volume":"326","author":"Epstein","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1161\/01.CIR.92.3.657","article-title":"Coronary plaque disruption","volume":"92","author":"Falk","year":"1995","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1056\/NEJM199203193261205","article-title":"Molecular and cellular biology of blood coagulation","volume":"326","author":"Furie","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/j.1538-7836.2004.00828.x","article-title":"Factor VIIa-mediated tenase function on activated platelets under flow","volume":"2","author":"Goel","year":"2004","journal-title":"J. Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1023\/B:THRO.0000011370.80989.7b","article-title":"Thrombin domains: structure, function and interaction with platelet receptors","volume":"15","year":"2003","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_21","unstructured":"Colman, R.W., Mardeer, V.J., Clowes, A.W., George, J.N., and Goldhaber, S.Z. (2006). Protease Activated Receptors in Hemostasis, Thrombosis, and Vascular Biology, Hemostasis and Thrombosis: Basic Principles and Clinical Practice, Lippincott, Williams, & Wilkins. [5th ed.]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/eurheartj\/ehp504","article-title":"Platelet thrombin receptor antagonism and atherothrombosis","volume":"31","author":"Angiolillo","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/35025229","article-title":"Thrombin signalling and protease-activated receptors","volume":"407","author":"Coughlin","year":"2000","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1161\/01.ATV.0000031340.68494.34","article-title":"Platelets and thrombin generation","volume":"22","author":"Monroe","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1172\/JCI114723","article-title":"Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors","volume":"86","author":"Weitz","year":"1990","journal-title":"J. Clin. Unvest."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1055\/s-0038-1648947","article-title":"The influence of fibrinogen and fibrin on thrombin generation evidence for feedback activation o f the clotting system by clot bound thrombin","volume":"72","author":"Kumar","year":"1994","journal-title":"Thromb. Haemost."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1055\/s-2006-939550","article-title":"An overview of the structure and function of thrombin","volume":"32","author":"Davie","year":"2006","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1160\/th14-03-0265","article-title":"Insights into the role of thrombin in the pathogenesis of recurrent ischaemia after acute coronary syndrome","volume":"112","author":"Weitz","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14777","DOI":"10.1074\/jbc.270.24.14477","article-title":"Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor","volume":"270","author":"Bajzar","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14477","DOI":"10.1074\/jbc.272.22.14477","article-title":"In the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B","volume":"272","author":"Sakharov","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1161\/01.CIR.91.1.28","article-title":"Plasmin-mediated activation of contact system in response to pharmacological thrombolysis","volume":"91","author":"Ewald","year":"1995","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/0049-3848(88)90329-5","article-title":"Differential effects of activation of prothrombin by streptokinase compared with urokinase and tissue-type plasminogen activation (t-PA)","volume":"50","author":"Eisenberg","year":"1998","journal-title":"Thromb. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0268-9499(93)90031-P","article-title":"Prothrombin activation by thrombolytic agents","volume":"7","author":"Seitz","year":"1993","journal-title":"Fibrinolysis"},{"key":"ref_34","first-page":"463","article-title":"Effect of shear stress on clot structure formation","volume":"20B","author":"Glover","year":"1974","journal-title":"Trans. Am. Soc. Artif. Intern. Organs"},{"key":"ref_35","first-page":"89","article-title":"Thrombin and antithrombotics","volume":"24","author":"Fenton","year":"1998","journal-title":"Semin. Thormb. Hemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1056\/NEJMoa1109719","article-title":"TRACER Investigators. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes","volume":"366","author":"Tricoci","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s11886-012-0286-6","article-title":"Which antithrombin for whom? Identifying the patient population that benefits most from novel antithrombin agents","volume":"14","author":"Burke","year":"2012","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1160\/TH12-06-0403","article-title":"Parenteral anticoagulants in heart disease: Current status and perspectives (Section II). Position paper of the ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease","volume":"109","author":"Husted","year":"2013","journal-title":"Thromb. Haemost."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCINTERVENTIONS.109.884478","article-title":"Anticoagulant therapy for percutaneous coronary intervention","volume":"3","author":"Rao","year":"2010","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s11886-011-0228-8","article-title":"Promise of factor Xa inhibition in acute coronary syndromes","volume":"14","author":"Lee","year":"2012","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1016\/j.jacc.2007.01.093","article-title":"Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial","volume":"49","author":"Gibson","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1056\/NEJMoa052711","article-title":"Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention","volume":"355","author":"Montalescot","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1056\/NEJMoa055443","article-title":"Comparison of fondaparinux and enoxaparin in acute coronary syndromes","volume":"354","author":"Yusuf","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1001\/jama.295.13.joc60038","article-title":"Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: The OASIS-6 randomized trial","volume":"295","author":"Yusuf","year":"2006","journal-title":"JAMA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"12P","DOI":"10.1016\/S0002-9149(98)00660-2","article-title":"Direct thrombin inhibitors for treatment of arterial thrombosis: potential differences between bivalirudin and hirudin","volume":"82","author":"Bates","year":"1998","journal-title":"Am. J. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s11239-015-1288-1","article-title":"Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants","volume":"41","author":"Ansell","year":"2016","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/ejh.12610","article-title":"Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives","volume":"95","author":"Lecumberri","year":"2015","journal-title":"Eur. J. Haematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1093\/europace\/eut083","article-title":"European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation","volume":"15","author":"Heidbuchel","year":"2013","journal-title":"Europace"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1160\/TH15-02-0158","article-title":"\u201cRealworld\u201d use of non-vitamin K antagonist oral anticoagulants (NOACs): Lessons from the Dresden NOAC Registry","volume":"113","author":"Eikelboom","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_50","first-page":"11","article-title":"Past, present, and future of hirudin","volume":"21","author":"Markwardt","year":"1991","journal-title":"Haemostasis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7095","DOI":"10.1021\/bi00482a021","article-title":"Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin","volume":"29","author":"Maragonore","year":"1990","journal-title":"Biochemistry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1160\/TH12-10-0772","article-title":"General mechanisms of coagulation and targets of anticoagulants (Section I). Position Paper of the ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease","volume":"109","author":"Husted","year":"2013","journal-title":"Thromb. Haemost."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/bj2830737","article-title":"Thrombin-specific inhibition by an slow cleavage of hirulog-1","volume":"283","author":"Witting","year":"1992","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14807","DOI":"10.1021\/bi00253a020","article-title":"Kinetic mechanism for the interaction of Hirulog with thrombin","volume":"33","author":"Parry","year":"1994","journal-title":"Biochemistry"},{"key":"ref_55","first-page":"27F","article-title":"The mechanism of action of thrombin inhibitors","volume":"12","author":"Bates","year":"2000","journal-title":"J. Invasive Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1160\/TH07-10-0644","article-title":"Bivalirudin","volume":"99","author":"Warkentin","year":"2008","journal-title":"Thromb Haemost."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0149-2918(02)85004-4","article-title":"Bivalirudin: a direct thrombin inhibitor","volume":"24","author":"Gladwell","year":"2002","journal-title":"Clin. Ther."},{"key":"ref_58","unstructured":"(2005). Angiomax\u2122 (Package insert) Parsippany, The Medicines Company."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1067\/mcp.2002.124522","article-title":"Bivalirudin pharmacokinetics and pharmacodynamics: Effect of renal function, dose, and gender","volume":"71","author":"Robson","year":"2002","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1161\/01.CIR.88.4.1495","article-title":"Initial experience with a direct antithrombin, Hirulog, in ustable angina. Anticoagulant, antithrombotic and clinical effects","volume":"88","author":"Juneau","year":"1993","journal-title":"Circulation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1161\/01.CIR.87.5.1622","article-title":"Use of a direct antithrombin, Hirulog, in place of heparin during coronary angioplasty","volume":"87","author":"Topol","year":"1993","journal-title":"Circulation"},{"key":"ref_62","first-page":"41F","article-title":"Dosage, pharmacological effects and clinical outcomes for bivalirudin in percutaneous coronary intervention","volume":"12","author":"Lui","year":"2000","journal-title":"J. Invasive Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1056\/NEJM199509213331204","article-title":"Adelman B, for the Hirulog Angioplasty Study Investigatiors. Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina","volume":"333","author":"Bittl","year":"1995","journal-title":"N. Engl. K. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1055\/s-0038-1656078","article-title":"Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass: Assessment of the whole blood ecarin clotting time","volume":"77","author":"Hund","year":"1997","journal-title":"Thromb. Haemost."},{"key":"ref_65","first-page":"383","article-title":"Bivalirudin monitored with the ecarin clotting time for anticoagulation during cardiopulmonary bypass","volume":"96","author":"Koster","year":"2003","journal-title":"Anesth. Analg."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1248\/bpb.34.1841","article-title":"Pharmacokinetics, pharmacodynamics, tolerability and safety of single doses of bivalirudin in healthy chinese subjects","volume":"34","author":"Zhang","year":"2011","journal-title":"Biol. Pharm. Bull."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-0038-1651573","article-title":"Anticoagulant activity of Hirulog, a direct thrombin inhibitor, in humans","volume":"69","author":"Fox","year":"1993","journal-title":"Thromb. Haemost."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1056\/NEJMoa0708191","article-title":"Bivalirudin during primary PCI in acute myocardial infarction","volume":"358","author":"Stone","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1056\/NEJMoa1311096","article-title":"Bivalirudin started during emergency transport for primary PCI","volume":"369","author":"Steg","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jcin.2014.11.002","article-title":"Acute stent thrombosis after primary percutaneous coronary intervention: insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography)","volume":"8","author":"Clemmensen","year":"2015","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/S0140-6736(14)60924-7","article-title":"Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): An open-label, single centre, randomised controlled trial","volume":"384","author":"Shahzad","year":"2014","journal-title":"Lancet"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1001\/jama.2015.2323","article-title":"Bivalirudin vs. heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: The BRIGHT randomized clinical trial","volume":"313","author":"Han","year":"2015","journal-title":"JAMA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1093\/eurheartj\/ehu182","article-title":"Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction","volume":"35","author":"Schulz","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1016\/j.jacc.2005.12.077","article-title":"A randomized trial to evaluate the relative protection against post-percutaneous coronary intervention microvascular dysfunction, ischemia, and inflammation among antiplatelet and antithrombotic agents: The PROTECT-TIMI-30 trial","volume":"47","author":"Gibson","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1016\/j.jacc.2007.12.052","article-title":"Safety and efficacy of switching from either unfractionated heparin or enoxaparin to bivalirudin in patients with non-ST-segment elevation acute coronary syndromes managed with an invasive strategy: Results from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial","volume":"51","author":"White","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jacc.2012.02.044","article-title":"Prognostic value of a high on-clopidogrel treatment platelet reactivity in bivalirudin versus abciximab treated non-ST-segment elevation myocardial infarction patients. ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy","volume":"60","author":"Sibbing","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1093\/eurheartj\/ehs215","article-title":"ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation","volume":"33","author":"Steg","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_78","first-page":"E1","article-title":"2013 ACCF\/AHA guideline for the management of ST-elevation myocardial infarction: Executive summary: A report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines: Developed in collaboration with the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions","volume":"82","author":"Kushner","year":"2013","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"ref_79","unstructured":"National Clinical Guideline Centre (UK) (2013). Myocardial Infarction with ST-Segment Elevation: The Acute Management of Myocardial Infarction with ST-Segment Elevation [Internet], Royal College of Physicians (UK)."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1093\/eurheartj\/ehu278","article-title":"2014 ESC\/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI)","volume":"35","author":"Windecker","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"National Clinical Guideline Centre (UK) (2010). Unstable Angina and NSTEMI: The Early Management of Unstable Angina and Non-ST-Segment-Elevation Myocardial Infarction, Royal College of Physicians (UK).","DOI":"10.1016\/B978-0-323-04107-2.50025-9"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/eurheartj\/ehv320","article-title":"2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)","volume":"37","author":"Roffi","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1016\/j.jacc.2014.09.017","article-title":"2014 AHA\/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"64","author":"Amsterdam","year":"2014","journal-title":"J. Am. Coll Cardiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMoa1507854","article-title":"Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes","volume":"373","author":"Valgimigli","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e000258","DOI":"10.1136\/openhrt-2015-000258","article-title":"Bivalirudin versus unfractionated heparin: A meta-analysis of patients receiving percutaneous coronary intervention for acute coronary syndromes","volume":"2","author":"Farag","year":"2015","journal-title":"Open Heart"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e002789","DOI":"10.1161\/CIRCINTERVENTIONS.115.002789","article-title":"Factors Affecting Bleeding and Stent Thrombosis in Clinical Trials Comparing Bivalirudin With Heparin During Percutaneous Coronary Intervention","volume":"8","author":"Bittl","year":"2015","journal-title":"Circ. Cardiovasc Interv."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jcin.2014.10.003","article-title":"Comprehensive meta-analysis of safety and efficacy of bivalirudin versus heparin with or without routine glycoprotein IIb\/IIIa inhibitors in patients with acute coronary syndrome","volume":"8","author":"Navarese","year":"2015","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1160\/TH14-08-0646","article-title":"Early stent thrombosis with bivalirudin in patients undergoing percutaneous coronary intervention. A meta-analysis of randomised clinical trials","volume":"113","author":"Piccolo","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_89","first-page":"209","article-title":"Bivalirudin Versus Heparin: A Fight Far From Finished?: Efficacy, Safety, and Cost Remain Battlegrounds for the Treatment Of ST-Segment Elevation Myocardial Infarction","volume":"40","author":"Alexander","year":"2015","journal-title":"Pharm. Ther."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/3\/284\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:19:50Z","timestamp":1760210390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/3\/284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,27]]},"references-count":89,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3]]}},"alternative-id":["molecules21030284"],"URL":"https:\/\/doi.org\/10.3390\/molecules21030284","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,27]]}}}