Pharmacotherapy for stroke prevention in nonvalvular atrial fibrillation: current strategies and future directions

ABSTRACT

Introduction

Cardioembolic stroke, associated to nonvalvular atrial fibrillation (NVAF), accounts for approximately one in every four strokes. Cardioembolic stroke has a bad prognosis and is associated with a significant rate of recurrence.

Areas covered

This article reviews current pharmacotherapeutic options for prevention of stroke in NVAF, paying special attention to their use in particular clinical settings (e.g. cardioversion, catheter ablation). We also aim to review new drug candidates that have entered clinical studies in this indication.

Expert opinion

Oral anticoagulant therapy (OAT) remains the mainstay for ischemic stroke prophylaxis in NVAF in patients at risk. Several oral (asundexian, milvexian) and parenteral (abelacimab, osocimab, xisomab, IONIS-FXI_RX, fesomersen) factor XIa inhibitors are under development. These new compounds appear to be associated with a low bleeding tendency and have the potential to complement current existing alternatives for anticoagulation. However, it is also of paramount importance to implement interventions to improve adherence to available anticoagulants, which is currently suboptimal. Non-anticoagulant drugs, such as colchicine, metformin and dronedarone, also being investigated to reduce the burden of NVAF and cardioembolic stroke. Additional clinical data are needed to more clearly define the role of these drugs for stroke prevention in NVAF.

KEYWORDS:

• Atrial fibrillation
• stroke
• anticoagulation
• DOAC
• VKA
• asundexian
• milvexian
• osocimab
• xisomab
• IONIS-FXI_RX
• fesomersen

Article highlights

• OAT remains the mainstay for ischemic stroke prophylaxis in NVAF in patients at risk.

• Real-world data indicate that adherence to OAT is still suboptimal and this is associated to poorer clinical outcomes. Measures to improve adherence are urgently needed.

• Several oral (asundexian, milvexian) and parenteral (abelacimab, osocimab, xisomab, IONIS-FXI_RX and fesomersen) factor XIa inhibitors are under development for the prevention of thromboembolism.

• New compounds appear to be associated with a low bleeding tendency and have the potential to complement current existing alternatives for anticoagulation.

• Other medications, such as colchicine, metformin and dronedarone are also being investigated to reduce the burden of AF and its complications, including stroke. Additional clinical data are needed to more clearly define the role of these drugs for stroke prevention in NVAF.

• This box summarizes key points contained in the article.

Acknowledgments

The opinions expressed in this review are of the authors alone and they do not necessarily represent the view of their institution or any other party.

Declaration of interest

Alejandro-Isidoro Pérez-Cabeza has received personal fees for lectures and consultancies from Bayer Hispania, Boehringer Ingelheim and Daiichi Sankyo, and personal fees for lectures from Bristol Myers Squibb and Pfizer outside the submitted work. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

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

Additional information

Funding

This paper was not funded.