Thromb Haemost 2015; 113(04): 698-707
DOI: 10.1160/TH14-09-0765
Review Article
Schattauer GmbH

Bivalirudin for acute coronary syndromes: premises, promises and doubts

Davide Capodanno
1   University of Catania, Catania, Italy
,
Raffaele De Caterina
2   G. d’Annunzio University, Chieti, Italy
› Author Affiliations
Further Information

Publication History

Received: 28 June 2014

Accepted after major revision: 10 October 2014

Publication Date:
24 November 2017 (online)

Summary

Bivalirudin is a valuable anticoagulant option in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention. Advantages over heparin as a parenteral anticoagulant include more predictable pharmacokinetics and pharmacodynamics, shorter half-life, no need for cofactors, some degree of antiplatelet effect, and the ability to inhibit clot-bound thrombin. Clinical evidence supporting the use of bivalirudin over heparin in current ACS guidelines, however, derives mostly from early randomised trials that may no longer reflect current management patterns, now including the use of oral antiplatelet agents more potent than clopidogrel (i.e. prasugrel or ticagrelor) and a broader implementation of strategies to reduce bleeding (i.e. radial access for percutaneous coronary intervention, and use of glycoprotein IIb/IIIa inhibitors only in bailout situations). Defining the fine balance between bivalirudin efficacy and safety over heparins in the context of other antithrombotic treatments remains a challenge in clinical practice, particularly in a fast-evolving scenario, such as ACS, where numerous new trials have been presented in very recent times. Here we provide an up-to-date overview of the evidence on the use of bivalirudin in ACS, with focus on new data, open issues, and future directions.

 
  • References

  • 1 De Caterina R. et al. 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. Thromb Haemost 2013; 109: 569-579.
  • 2 De Caterina R. et al. 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. Thromb Haemost 2013; 109: 769-786.
  • 3 Capodanno D, Angiolillo DJ. Antithrombotic therapy in patients with chronic kidney disease. Circulation 2012; 125 (21) 2649-2661.
  • 4 O’Gara PT. et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61: e78-e140.
  • 5 Anderson JL. et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/ non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61: e179-e347.
  • 6 Stone GW. et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355: 2203-2216.
  • 7 Stone GW. et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218-2230.
  • 8 Windecker S. et al. 2014 ESC/EACTS Guidelines on myocardial revascularisation: The Task Force on Myocardial Revascularisation 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). Eur Heart J. 2014. Epub ahead of print
  • 9 Kastrati A. et al. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med 2011; 365: 1980-1989.
  • 10 Steg PG. et al. Bivalirudin started during emergency transport for primary PCI. N Engl J Med 2013; 369: 2207-2217.
  • 11 Schulz S. et al. Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2014. Epub ahead of print; Epub ahead of print
  • 12 Shahzad A. et al. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet. 2014. Epub ahead of print
  • 13 Lip GY. et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Eur Heart J. 2014. Epub ahead of print
  • 14 Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. Lancet 2014; 384: 599-606.
  • 15 Cassese S. et al. Bivalirudin versus heparin in patients treated with percutaneous coronary intervention: a meta-analysis of randomised trials. EuroIntervention. 2014. Epub ahead of print
  • 16 De Servi S. et al. The bivalirudin paradox: high evidence, low use. J Cardiovasc Med 2013; 14: 334-341.
  • 17 Schulz S. et al. One-year outcomes with abciximab and unfractionated heparin vs bivalirudin during percutaneous coronary interventions in patients with non-ST-segment elevation myocardial infarction: updated results from the ISAR-REACT 4 trial. Eurointervention 2013; 09: 430-436.
  • 18 Sibbing D. et al. Prognostic value of a high on-clopidogrel treatment platelet reactivity in bivalirudin vs 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. J Am Coll Cardiol 2012; 60: 369-377.
  • 19 Ndrepepa G. et al. Bivalirudin vs heparin plus a glycoprotein IIb/IIIa inhibitor in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention after clopidogrel pretreatment: pooled analysis from the ACUITY and ISAR-REACT 4 trials. Circ Cardiovasc Interv 2012; 05: 705-712.
  • 20 Bangalore S. et al. Heparin Monotherapy or Bivalirudin During Percutaneous Coronary Intervention in Patients With Non-ST-Segment-Elevation Acute Coronary Syndromes or Stable Ischaemic Heart Disease: Results From the Evaluation of Drug-Eluting Stents and Ischaemic Events Registry. Circ Cardiovasc Interv. 2014. Epub ahead of print
  • 21 Krishnaswamy A. et al. The use and limitations of unfractionated heparin. Crit Pathw Cardiol 2010; 09: 35-40.
  • 22 White HD. et al. Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators. Circulation 1997; 96: 2155-2161.
  • 23 White H. Hirulog, Early Reperfusion or Occlusion –2 Trial I. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 2001; 358: 1855-1863.
  • 24 Mehran R. et al. Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial. Lancet 2009; 374: 1149-1159.
  • 25 Kirtane AJ. et al. Association between intraprocedural thrombotic events and adverse outcomes after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (a Harmonizing Outcomes With RevascularisatioN and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Substudy). Am J Cardiol 2014; 113: 36-43.
  • 26 Zeymer U. et al. Bivalirudin is superior to heparins alone with bailout GP IIb/ IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a prespecified analysis from the EUROMAX trial. Eur Heart J. 2014. Epub ahead of print
  • 27 Clemmensen P. et al. Predictors associated with acute stent thrombosis after primary PCI: the EUROMAX trial. J Am Coll Cardiol 2014; 63: 1_S.
  • 28 Zimarino et al. Isolated troponin increase after percutaneous coronary interventions: Does it have prognostic relevance?. Atherosclerosis 2012; 221 (02) 297-302.
  • 29 Berger PB, Blankenship JC. Is the heat on HEAT-PPCI appropriate?. Lancet. 2014. Epub ahead of print
  • 30 Parodi G. et al. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study. Am Heart J 2014; 167: 909-914.
  • 31 Alexopoulos D. et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2012; 05: 797-804.
  • 32 Shelton R. et al. Bivalirudin in patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: outcomes in a large real-world population. Eurointervention 2013; 09: 118-124.
  • 33 Hibbert B. et al. Bivalirudin for primary percutaneous coronary interventions: outcome assessment in the Ottawa STEMI registry. Circ Cardiovasc Interv 2012; 05: 805-812.
  • 34 Latour-Perez J, de-Miguel-Balsa E. Cost effectiveness of anticoagulation in acute coronary syndromes. Pharmacoeconomics 2012; 30: 303-321.
  • 35 Schwenkglenks M. et al. Cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor in the treatment of non-ST-segment elevation acute coronary syndromes. Value Health 2011; 14: 24-33.
  • 36 Schwenkglenks M. et al. Cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor in the treatment of acute ST-segment elevation myocardial infarction. Heart 2012; 98: 544-551.
  • 37 Steg PG. et al. Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J 2011; 32: 1854-1864.
  • 38 Kadakia MB. et al. Use of anticoagulant agents and risk of bleeding among patients admitted with myocardial infarction: a report from the NCDR ACTION Registry--GWTG (National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry--Get With the Guidelines). JACC Cardiovasc Interv 2010; 03: 1166-1177.
  • 39 Valgimigli M. et al. Scientific foundation and possible implications for practice of the Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX (MATRIX) trial. J Cardiovasc Transl Res 2014; 07: 101-111.