Bivalirudin in acute coronary syndromes

ABSTRACT

Introduction

Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Areas covered

Despite showing a superior safety profile compared with unfractionated heparin (UFH), bivalirudin is not considered the anticoagulant of choice in ACS patients undergoing PCI, mainly because of an increased rate of acute stent thrombosis (ST) shown by several randomized controlled trials (RCTs), in addition to limited availability in certain countries and increased costs. However, RCTs on bivalirudin have been characterized by several confounding factors hindering the interpretation of its safety and efficacy compared with UFH among the spectrum of ACS patients. Furthermore, a significant body of evidence has demonstrated that the risk of acute ST can be mitigated by a full-dose infusion regimen following PCI, without compromising the favorable safety profile compared to UFH.

Expert opinion

In light of the increased understanding of the prognostic relevance of bleeding events and the excellent safety profile of bivalirudin, recent trial evidence may allow for this anticoagulant agent to reemerge and have a more prominent role in the management of ACS patients undergoing PCI.

KEYWORDS:

• Bivalirudin
• acute coronary syndrome
• heparin
• post-PCI infusion
• ST-segment myocardial infarction
• non-ST-segment myocardial infarction

Article highlights

• Bivalirudin is a synthetic 20-amino acid peptide deriving from hirudin that directly inhibits thrombin by binding thrombin catalytic site. It is characterized by fast onset of action (~5 min) and short half-life (~25 min), enabling for prompt and effective anticoagulation also in the absence of an antidote.

• Randomized controlled trials (RCTs) have consistently shown increased safety profile of bivalirudin compared with unfractionated heparin (UFH), but its use has been downgraded by guidelines mainly because of an increased rates of acute stent thrombosis (ST).

• A significant body of evidence has demonstrated that the risk of acute ST could be mitigated by a full-dose regimen for a duration of 3 or 4 h following percutaneous coronary intervention (PCI), without any trade-off in bleeding compared to UFH.

• Several confounding factors of RCTs, such as the concomitant use of glycoprotein IIb/IIIa inhibitors, the use of different doses of bivalirudin infusion, the selective inclusion of East Asian patients, and the lower rate of radial access and low use of potent P2Y₁₂ inhibitors in early compared to more recent RCTs, have hindered the interpretation of the safety and efficacy of bivalirudin compared with UFH among the spectrum of ACS patients.

• The understanding of the pitfalls of previous trials has led to the design of modern day studies suggesting that bivalirudin may represent an effective and safer option compared with UFH in ACS patients undergoing PCI.

Declaration of interest

M Galli has received consulting fees from Terumo, outside the present work. G Biondi-Zoccai has consulted for Amarin, Balmed, Cardionovum, Crannmedical, Endocore Lab, Eukon, Guidotti, Innovheart, Meditrial, Microport, Opsens Medical, Terumo, and Translumina, outside the present work. F Franchi declares that he has received payment as an individual for consulting fee or honoraria from AstraZeneca, Bayer, and Sanofi, outside the present work; and institutional payments for grants from PLx Pharma and The Scott R. MacKenzie Foundation. DJ Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi and Vectura, outside the present work. DJ Angiolillo also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions and Scott R. MacKenzie Foundation.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Acknowledgments

Figures were created with Biorender.com

Additional information

Funding

Research leading to this work has received funding the European Union - NextGenerationEU, through the Italian Ministry of University and Research, under PNRR - M4C2-I1.3 Project PE_00000019 “HEAL ITALIA” to Giuseppe Biondi-Zoccai CUP B53C22004000006 Sapienza University of Rome. The views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them.