The clinical and economic impact of bivalirudin for percutaneous coronary intervention

Abstract

Bivalirudin (BVR) is a direct thrombin inhibitor used as an adjunctive antithrombotic agent in combination with aspirin and an ADP-receptor blocker in patients with acute coronary syndrome undergoing percutaneous coronary intervention. When compared to a strategy of heparin plus a glycoprotein IIb/IIIa inhibitor, BVR has been shown in a number of randomized clinical trials to be at least as effective at reducing ischemic endpoints and to have a consistently lower rate of bleeding complications. In addition, various economic analyses have shown it to be cost-effective compared to heparin plus a glycoprotein IIb/IIIa inhibitor and this, coupled with its proven clinical efficacy, has led to the incorporation of BVR into both EU and US clinical guidelines. Previous studies with BVR have mostly assessed its use in patients treated with aspirin and clopidogrel and further studies are ongoing to determine its role in combination with newer, more potent oral antiplatelet agents.

Keywords::

• bivalirudin
• bleeding
• clinical efficacy
• economic impact
• percutaneous coronary intervention

Financial & competing interests disclosure

AH Gershlick has been on the advisory board for and received honorarium payments from the Medicines Company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Bivalirudin (BVR) is a direct thrombin inhibitor used in addition to dual antiplatelet therapy in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) and high-risk non-ST elevation acute coronary syndrome (ACS) patients planned for urgent PCI.

• • When compared to a combination of heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), BVR has been shown to be non-inferior in terms of ischemic outcomes, except for an increase in acute stent thrombosis in STEMI patients treated with primary PCI in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial.

• • BVR has a favorable safety profile and when compared to a combination of heparin plus a GPI, it has consistently been found to be associated with less bleeding complications often leading to improved overall outcomes.

• • In the HORIZONS-AMI trial, comparing the use of BVR versus heparin plus a GPI in STEMI patients undergoing primary PCI, two-thirds of patients in the BVR ‘monotherapy’ arm had been given a prior bolus dose of unfractionated heparin (UFH). This is not reflected in the clinical guidelines.

• • A number of economic evaluations for the use of BVR in various clinical settings have shown it to be cost-effective when compared to heparin plus a GPI.

• • BVR has been given a class I recommendation (level of evidence B) in EU and US guidelines for use as adjuvant antithrombotic therapy during primary PCI for STEMI and during PCI for unstable angina/NSTEMI.

• • There is currently only limited data for the use of BVR in combination with newer, more potent oral ADP-receptor antagonists and this is currently being addressed in two randomized clinical trials looking at its combination with prasugrel.

• • In the context of more potent antiplatelet agents, BVR will be compared to ‘heparin-only’ treatment in non-ST elevation ACS patients undergoing PCI in the upcoming VALIDATE-SCAAR trial, based on the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

• • The HEAT-PPCI study is comparing BVR therapy to UFH in STEMI patients undergoing primary PCI according to current and evolving standards, including more potent antiplatelet agents and predominant radial access.

• • Another clinical study, European Ambulance ACS Angiography trial (EUROMAX), is investigating whether the early administration of BVR can improve outcomes in STEMI patients presenting indirectly via ambulance or via a non-interventional center.