Does Bivalirudin Improve Outcomes in Contemporary Percutaneous Coronary Intervention?

Review Article

J Cardiovasc Disord. 2016; 3(1): 1020.

Does Bivalirudin Improve Outcomes in Contemporary Percutaneous Coronary Intervention?

Czarny MJ1, and Resar JR2*

1Division of Cardiology, Johns Hopkins Hospital, Baltimore, USA

2Division of Cardiology, Johns Hopkins Hospital, Baltimore, USA

*Corresponding author: Resar JR, Division of Cardiology, Johns Hopkins Hospital, 1800 Orleans St., 7E Room 7125NB3, Baltimore, USA

Received: November 18, 2015; Accepted: January 11, 2016; Published: January 13, 2016


Adequate anticoagulation is critical for successful Percutaneous Coronary Intervention (PCI). Unfractionated heparin has long been the standard, but bivalirudin quickly became an attractive alternative when early studies suggested a bleeding benefit without an increase in ischemic outcomes. Over the last 20 years, clinical trials have evaluated the relative efficacy and safety of heparin and bivalirudin across the spectrum of coronary artery disease presentations and in the setting of concomitant glycoprotein IIb/IIIa inhibitors, pre-treatment with oral antiplatelet agents, and radial rather than femoral arterial access. There is little doubt that bivalirudin monotherapy reduces bleeding when compared to heparin with routine glycoprotein IIb/IIIa inhibitor use, but this comparison is of diminishing relevance to contemporary PCI. Whether bivalirudin monotherapy is superior to heparin monotherapy remains the subject of much debate.

Keywords: Percutaneous Coronary Intervention; Anticoagulation; Unfractionated Heparin; Bivalirudin


ACUITY: Acute Catheterization and Urgent Intervention Triage Strategy; BARC: Bleeding Academic Research Consortium; BRIGHT: Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial; CAD: Coronary Artery Disease; EUROMAX: European Ambulance Acute Coronary Syndrome Angiography; GP IIb/IIIa inhibitor: Glycoprotein IIb/IIIa inhibitor; HEAT-PPCI: How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention; HORIZONS-AMI: Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction; ISAR-REACT 3: Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 3; ISARREACT 4: Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4; MACE: Major Adverse Cardiac Events; MATRIX: Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; MI: Myocardial Infarction; NACE: Net Adverse Clinical Events; NAPLES: Novel Approaches for Preventing or Limiting Events; NSTEMI: Non-ST Segment Elevation Myocardial Infarction; PCI: Percutaneous Coronary Intervention; REPLACE-2: Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events; STEMI: ST-segment Elevation Myocardial Infarction; TVR: Target Vessel Revascularization; UFH: Unfractionated Heparin


Percutaneous Coronary Intervention (PCI) is a common treatment for the full spectrum of Coronary Artery Disease (CAD). Effective antithrombotic therapy is absolutely critical to safe, successful PCI and prevents thrombus formation on the guide catheter, on guide wires, and at the site of intracoronary endothelial disruption resulting from balloon dilation and stent implantation. Intravenous Unfractionated Heparin (UFH) has long been the standard anticoagulant during PCI, but in the last 10 to 15 years the direct thrombin inhibitor bivalirudin has become an attractive alternative. Unlike UFH, bivalirudin does not require a cofactor and is active against both free and thrombus-bound thrombin [1]. Furthermore, the unpredictable pharmacokinetics of UFH in individual patients makes precise dosing difficult and result in somewhat unpredictable anticoagulant effects. Based on trials of bivalirudin monotherapy compared to UFH with routine glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor use, bivalirudin enjoys a reputation for less bleeding. However, GP IIb/IIIa inhibitors are no longer routinely used with UFH, so the currently relevant comparison is bivalirudin monotherapy to UFH monotherapy. Despite nearly 20 years of clinical trials, the relative advantages and disadvantages of bivalirudin monotherapy over UFH monotherapy remain unclear.

Trials in Non-Primary PCI

Major randomized clinical trials of UFH and bivalirudin in PCI are summarized in Table 1. The first major study of bivalirudin in PCI was the Hirulog Angioplasty Study which randomized 4098 patients with unstable angina or post-infarction angina undergoing balloon angioplasty to high-dose UFH (a bolus of 175 units/kg followed by a continuous infusion) or bivalirudin and showed no difference in inhospital death or ischemic outcomes in the per-protocol analysis [2]. However, in-hospital major hemorrhage occurred in 9.8% of patients receiving UFH but only 3.8% of patients receiving bivalirudin (P <0.001). Notably, the re-analysis of this study by the intention-totreat principle confirmed the bleeding advantage of bivalirudin up to 90 days (3.7% vs 9.3%, P <0.001), and additionally suggested a benefit for the composite of death, Myocardial Infarction (MI), or revascularization at 90 days (15.7% vs 18.5%, P = 0.012) which was not maintained at 180 days (23.0% vs 24.7%, P = 0.153) [3].

Citation: Czarny MJ and Resar JR. Does Bivalirudin Improve Outcomes in Contemporary Percutaneous Coronary Intervention?. J Cardiovasc Disord. 2016; 3(1): 1020. ISSN: 2379-7991