An update on novel therapies for treating patients with arterial thrombosis

ABSTRACT

Introduction

Antithrombotic therapy field is undergoing rapid and significant changes during the past decade. In addition to new therapeutic strategies with existing targets, investigators are exploring the potential use of new targets to address unmet needs to treat patients with arterial diseases.

Areas covered

We aim to provide an update on and a comprehensive review of the antithrombic agents that are being explored in patients with arterial diseases. We discuss latest developments with respect to upstream antiplatelet agents, and collagen and thrombin pathway inhibitors. We searched PubMed databases for English language articles using keywords: antiplatelet agents, thrombin pathway inhibitors, collagen receptors, arterial disease.

Expert opinion

Despite implementation of potent P2Y₁₂ inhibitors, there are numerous unmet needs in the treatment of arterial diseases including ceiling effect of currently available antiplatelet agents along with and an elevated risk of bleeding. The latter observations encouraged investigators to explore new targets that can attenuate the generation of platelet-fibrin clot formation and subsequent ischemic event occurrences with minimal effect on bleeding. These targets include collagen receptors on platelets and thrombin generation including FXa, FXIa, and FXIIa. In addition, investigators are studying novel antiplatelet agents/strategies to facilitate upstream therapy in high-risk patients.

KEYWORDS:

• antithrombotic agents
• arterial thrombosis
• acetyl salicylic acid
• P2Y₁₂ receptor
• GPVI receptor
• GPIIb/IIIa receptor
• FXA
• FXIa
• FXIIa

Article highlights

• New formulations of aspirin and P2Y₁₂ receptor inhibitors are being explored for upstream treatment in high-risk arterial disease patients.

• Novel antiplatelet agents targeting GPIIb/IIIa receptor, thrombin receptor and collagen receptors are in the development.

• These agents may overcome some of the unmet needs of the currently available antiplatelet agents.

• Inhibitors of ‘thrombin pathway’ are also being explored in recent trials. In addition to currently available FXa inhibitor (very low dose rivaroxaban) for arterial thrombosis, FXIa and FXIIa inhibitors are being explored in clinical trials.

Declaration of interest

PA Gurbel has received consulting fees and/or honoraria from Bayer, Otitopic, Janssen, UpToDate, Cleveland Clinic, Adeno, Wolters Kluwer Pharma, Web MD Medscape, Baron and Budd, North American Thrombosis Forum, Innovative Sciences; institutional research grants from the Haemonetics, Janssen, Bayer, Instrumentation Laboratories, Amgen, Idorsia, Otitopic, Hikari Dx, Novartis, Precision Biologic, Nirmidas Biotech, and R-Pharma International; in addition, PA Gurbel has two patents, Detection of restenosis risk in patients issued and Assessment of cardiac health and thrombotic risk in a patient. PA Gurbel was an expert witness in a lawsuit associated with Plavix.

E Navarese reports speaker and consultancy fees from Amgen, Sanofi-Regeneron, Bayer, and grants from Abbott.

U Tantry reports consulting fees from UpToDate.

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 or other relationships to disclose.

Additional information

Funding

This work was not funded.