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News & Articles > Bivalirudin or heparin in patients undergoing invasive management of ACS


Originally published as an update to Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 11th edition

Debra L. Beck and Eugene Braunwald, MD

Date Published: 06 July 2018


Bivalirudin or heparin in patients undergoing invasive management of ACS

There are conflicting data on the comparative safety and effectiveness of bivalirudin compared with unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs). The issue has been made more unclear with the expansion of antithrombotic therapies available for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), which has led to a reduction in planned GPI use. This analysis of the MATRIX trial assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with ACS who underwent invasive management.


In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) trial, 7,213 patients with ACS were randomly assigned to receive either bivalirudin (with GPIs restricted to bailout use) or UFH (with GPIs use left to the discretion of the operator). Among the 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups at 4.5% and 5.4%, respectively (p=0.11).


At 30 days, no differences were seen between the 3 groups in terms of the 2 coprimary endpoints of MACEs (death, MI, stroke) and NACEs (MACE or major bleeding) in either multivariable or propensity-adjusted models. Similarly, there were no within-group differences in the individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke.


However, compared to those who received UFH or UFH + planned GPI, bivalirudin consistently reduced major bleeding, including fatal and nonaccess site-related events, transfusion rates, and the need for surgical access site repair. These findings were also consistent in multivariable, propensity score-adjusted, and propensity score-matched analyses, and were not influenced by randomly allocated access site or intraprocedural dose of UFH.


Stent thrombosis trended higher and mortality lower with bivalirudin compared to UFH or UFH+GPI, but none of the single components of the coprimary composite endpoints differ significantly other than bleeding.



The investigators concluded that, in ACS patients, composite adverse outcomes did not differ with bivalirudin compared to UFH, irrespective of planned GPI use, but bivalirudin was associated with significantly less bleeding.



“…the findings of this elegant analysis are noteworthy and of clinical value,” wrote Angiolillo et al in an editorial, although the findings need to be viewed with caution in the context of a trial that did not meet its primary outcome and was underpowered for mortality. However, if a larger analysis finds a mortality benefit for bivalirudin (and it would have to come from a retrospective analysis because a suitable trial of the issue is unlikely to ever be done), this might trump the increased cost associated with the drug. Also, said the editorialists, dedicated investigations on the role of bivalirudin in high bleeding risk settings are warranted.


  1. G Gargiulo, G Carrara, E Frigoli, et al: Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes. J Am Coll Cardiol. 71(11): 1231-1242. 2018 Mar 20. 29544607
  2. DJ Angiolillo, F Rollini, F Franchi: The Quest for the Optimal Periprocedural Antithrombotic Treatment Strategy in ACS Patients Undergoing PCI. J Am Coll Cardiol. 71(11): 1243-1245. 2018 Mar 20. 29544608


Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine features a unique update program by Dr. Braunwald, creating a “living textbook” by featuring weekly Hot off the Press, periodic Late-Breaking Clinical Trials (including links to authors’ presentation slides), and monthly Focused Reviews.

Learn more about Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 11th Edition. Download a free chapter here.

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