Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. It occurs when the upper chambers of the heart (the atria) beat irregularly and often too fast (more than 400 beats per minute). In persistent AF, this irregular rhythm doesn’t resolve independently and lasts longer than seven days, often requiring medical treatment to restore a normal heartbeat.¹ 

AF affected over 33 million people in 2019. Its prevalence has surged significantly, doubling from 28 million cases in 1990 to nearly 57 million by 2019, with projections indicating further increases in the coming decades. In Europe alone, AF is expected to affect 14.4 million individuals over the age of 65 by 2060, marking an 89% rise compared to 2016.^2,3 

The burden of AF varies globally. High-income regions, such as North America and Europe, have seen rapid increases due to ageing populations and lifestyle factors like obesity and high blood pressure. Meanwhile, middle-income countries are experiencing the fastest growth in AF-related morbidity and mortality. Deaths linked to AF have risen sharply, with increases of over 200% in lower-middle-income countries between 1990 and 2019.^2,3 

People with atrial fibrillation are at a much higher risk of stroke, around five times more likely than those with a normal heart rhythm. This is because an irregular heartbeat can cause blood to pool and form clots in the heart, which can then travel to the brain.⁴

This article highlights the importance of persistent AF and how anticoagulation therapy plays a crucial role in preventing strokes and saving lives.

Understanding persistent atrial fibrillation 

AF comes in different forms, depending on how long it lasts and whether it resolves on its own. Paroxysmal AF comes and goes on its own within seven days, usually within 48 hours. Persistent AF lasts longer than seven days and often needs medical treatment like medication or cardioversion to bring the heart back to a normal rhythm. If the condition continues despite treatment, it may become permanent AF.¹ 

In persistent AF, the electrical signals in the atria become disorganised, causing the heart to beat irregularly. This disrupts how blood flows through the heart and can lead to the formation of clots, especially in the left atrial appendage (LAA).⁵

Several factors increase the risk of developing AF, including older age, high blood pressure, heart failure, diabetes, obesity, and sleep apnea. Some people notice palpitations, fatigue, or shortness of breath, while others might not feel any symptoms at all. AF is typically diagnosed using an electrocardiogram (ECG) or Holter monitor, which records the heart’s rhythm over time.¹ 

Stroke risk in atrial fibrillation patients 

When the heart beats irregularly, especially in persistent AF, it doesn’t pump blood through the atria as effectively. This can cause blood to pool, particularly in a small pouch called the LAA, which increases the chance of clots forming. Hence, the risk of thrombus formation is higher, leading to embolic strokes, meaning that if a clot breaks free and travels to the brain, it can block blood flow and lead to a stroke.^1,6

People with AF are four to five times more likely to have a stroke than those without it. Not only are strokes more common in AF patients, but they also tend to be more severe and are associated with higher rates of disability and death.⁶ 

To assess stroke risk in people with AF, doctors use a scoring system called CHA₂DS₂-VASc. This tool considers several factors:⁷

• Congestive heart failure
• Hypertension
• Age 75 or older (2 points)
• Diabetes
• Stroke or TIA history (2 points)
• Vascular disease
• Age 65–74
• Sex category

A score of 2 or more in people assigned as male at birth, or 3 or more in people assigned as female at birth, typically indicates the need for anticoagulation therapy to lower stroke risk.⁷

Anticoagulation therapy: role and options

The primary aim of anticoagulation therapy in AF is to prevent thromboembolic events, particularly ischaemic stroke. By reducing the formation of blood clots in the atria, anticoagulants play a central role in improving outcomes for patients with persistent AF.⁸

Historically, vitamin K antagonists (VKAs), most notably warfarin, have been the primary treatment option for stroke prevention in AF. Warfarin works by inhibiting vitamin K-dependent clotting factors, thereby reducing blood coagulability. However, regular international normalised ratio (INR) monitoring is required to ensure therapeutic levels (typically between 2.0 and 3.0), and its effectiveness can be affected by diet, other medications, and genetic factors. While warfarin is effective, it narrows the therapeutic window, requiring frequent dose adjustments and higher bleeding risk, which has led to the development of alternative options.^9,10

Recently, Direct Oral Anticoagulants (DOACs) have become increasingly preferred. This class includes dabigatran (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (factor Xa inhibitors). DOACs offer several advantages over warfarin: they have predictable pharmacokinetics, do not require routine monitoring, have fewer drug and food interactions, and are associated with a lower risk of intracranial bleeding. DOACs are now considered first-line therapy for most patients. However, warfarin may still be used in cases where DOACs are not indicated.¹⁰ 

Balancing stroke prevention with bleeding risk

While anticoagulation therapy significantly reduces the risk of stroke in patients with AF, it also introduces a potential risk of bleeding. Therefore, treatment decisions must carefully weigh the benefits of stroke prevention against the individual’s bleeding risk.¹¹

The HAS-BLED score is a widely used clinical tool to estimate bleeding risk in patients on anticoagulation. It evaluates factors such as hypertension, abnormal renal or liver function, stroke history, bleeding history, labile INR, age over 65, and use of drugs or alcohol. A score of 3 or more indicates a higher bleeding risk and signals the need for closer monitoring, not necessarily to withhold anticoagulation but to manage modifiable risk factors.¹²

Regular patient review and shared decision-making are essential. This ensures that therapy remains appropriate over time and allows clinicians to adjust treatment based on changes in the patient’s health, preferences, or concurrent medications. Strategies to minimise bleeding risk include accurate dosing, especially with DOACs (which are often weight- and renal function-dependent), routine renal function checks, and educating patients on medication adherence, signs of bleeding, and avoiding over-the-counter drugs that increase bleeding risk, such as NSAIDs.¹²

Summary

Persistent AF significantly increases the risk of stroke due to irregular heart rhythms that promote blood clot formation, particularly in the left atrial appendage. Anticoagulation therapy plays a vital role in reducing this risk. This article explored the pathophysiology of persistent AF, outlines stroke risk assessment using the CHA₂DS₂-VASc score, and reviews anticoagulation options, including warfarin and DOACs. It also discusses bleeding risk management using the HAS-BLED score and highlights the importance of regular patient review, proper dosing, and shared decision-making. Ultimately, effective anticoagulation in AF requires a careful balance between stroke prevention and bleeding risk, guided by clinical tools and patient-specific considerations.