Subclinical AF and Increased Stroke Risk: Is There a Clear Connection?

The average lifespan is increasing in most parts of the globe, triggering a corresponding increase in the prevalence of atrial fibrillation (AF) across many demographics.¹ Symptomatic AF is known to significantly increase lifetime risk of thrombotic events (TEs), and general wisdom supports the use of oral anticoagulants (OACs) in patients with symptomatic AF.

However, many clinicians struggle to determine whether OAC is an appropriate treatment for subclinical atrial fibrillation (SCAF). According to a meta-analysis published in Biomedical Papers, there is insufficient evidence supporting the link between some forms of SCAF and an increased risk of TE. The meta-analysis concludes that clinicians must judge each patient’s risk factors to determine if anticoagulant therapy is appropriate.¹

Understanding the Recent Increase in AF Cases

AF is strongly associated with increased age, and because of increased lifespans and progress with AF diagnostic techniques, an ever-increasing number of people have been diagnosed with SCAF. These individuals may experience no symptoms and may be unaware of their condition for many years. Often, SCAF is only diagnosed after a stroke or heart failure.

However, the link between SCAF and increased thromboembolic risk is currently unclear. A systematic review by Mahajan et al revealed that the stroke risk in individuals with SCAF was 1.89, but the risk was only 0.93 in patients without SCAF.² However, some clinicians have speculated that comorbid conditions and other risk factors may play a significant role in determining risk for TE. As a result, global treatment guidelines for SCAF have yet to be standardized.

Although some studies indicate that SCAF episodes lasting longer than 24 hours are associated with a significant increase in the risk for TEs,² there is no standardized threshold for beginning anticoagulation therapy. Many individuals with SCAF do not experience stroke or heart failure during their lifetime. Thus, evidence supporting the use of OACs to treat SCAF when additional TE risk factors are not present remains weak.

Prevalence of AF and Stroke Risk

Overall, 2.3% of individuals have AF by age 40, and by age 65, the prevalence of AF rises to 6%.¹ Numbers continue to increase with age, with AF is present in almost 20% of the population aged 80 and older.¹

Additionally, the meta-analysis confirmed a strong link between AF and lifetime risk of thromboembolic events. When risk factors were adjusted to reflect the patient’s age, individuals with AF were determined to be 5 times more likely to experience a stroke than the general population.¹

However, clinicians must recall that the groups analyzed in these studies include patients with symptomatic AF and possibly other comorbidities. The link between SCAF and thromboembolic events is even less clear. SCAF may increase the risk of developing detectable forms of AF, but this increased risk does not always translate to a risk of TE or a need for anticoagulant therapy.

Defining and Diagnosing AF

Before clinicians can use the data from recent studies to guide treatment decisions for SCAF, it is essential to consider the SCAF thresholds analyzed in recent studies. Regrettably, this process can be a challenge: the meta-analysis revealed that many studies use varying thresholds to interpret atrial high-rate episodes (AHRE).¹

Clinicians often rely on cardiac implantable devices (CIEDs), such as external loop recorders and pacemakers, to diagnose SCAF. These devices are an excellent tool for quickly identifying AF and assessing the severity of the condition. However, device manufacturers often have different thresholds for evaluating the severity and duration of AHRE and may not log episodes that fail to meet these thresholds,¹ and these data are sometimes excluded from medical studies.

“The AF detection algorithms are in most cases correct…there are, however, several limitations,” noted the meta-analysis. “[F]alse positive AF detections may occur in 2% to 20% [of patients] depending on the tip to ring electrode spacing and position of the atrial lead.¹ The other issue of CIEDs is atrial undersending, causing underdetection of AF.”

Although CIEDs are an essential tooth for detecting and managing SCAF, clinicians are still responsible for interpreting CIED data and using the data parameters to guide treatment decisions. At present, it is not always clear which parameters should be considered to determine when to start anticoagulant treatment.

The length and frequency of AHRE episodes may play a significant role in assessing stroke risk. However, the reliability of the device’s algorithms can sometimes be called into question. In other cases, there may be inconsistencies between the data provided by CIEDs and the clinician’s ECG results. Even when SCAF is confirmed, clinicians are left to determine whether the diagnosis represents a significant indicator of stroke risk, or if it is merely one of many risk factors. At present, a direct temporal link between SCAF and stroke is still unproven.²

Clinical Data Regarding Stroke Risk

The Framingham Heart Study indicates that the risk of AF-related thromboembolic events rises steadily between the ages of 50 to 80, from 1.5% to 24%, respectively.³ Further, approximately 17% of strokes are attributed to AF, and AF-related strokes are often linked to a higher mortality rate.³ It is still unclear whether these numbers reflect the risks of SCAF.

During the TRENDS and ASSERT trials considered in the meta-analysis, AF episodes were detected in the 30 days preceding stroke in 55% and 22% of patients, respectively.² Stronger links were observed in those experiencing AHRE less than 30 days before a stroke. SCAF episodes lasting longer than 24 hours were also associated with an increased risk of stroke.¹

It is also unclear whether the frequency of AHRE has an impact on the risk of TE. Episodes of longer than 5 minutes of device-detected AF were associated with an increased risk of TE.¹ This risk was further increased with the duration of the AHRE, but the researchers concluded that “[w]e have insufficient data to confirm that the frequency during AHRE plays any role in the stroke risk.”

The Use of OAC in Patients With SCAF

Current treatment guidelines are contradictory and do not provide sufficient evidence for clinicians to conclusively determine whether the use of OAC is advisable in patients with SCAF.

The ASSERT study guidelines advise starting anticoagulation therapy if AHREs last for 5 minutes or longer with a rate greater than 180/min.¹ Clinicians are advised to verify the presence of AF through ECG or a review of CIED data. EHRA guidelines suggest beginning OAC if the AF burden exceeds 5.5 h/day.² Some individuals below that threshold may also benefit from OAC if there are multiple risk factors present.

The inconsistency between these recommendations may leave many clinicians without clear-cut guidelines for determining when to begin OAC. In general, the meta-analysis concluded, clinicians must adopt an individualized approach to assessing patient risk factors to select the best treatment strategy.

References

1. Plasek J, Taborsky M. Subclinical atrial fibrillation – what is the risk of stroke? [published online January 10, 2019]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. doi:10.5507/bp.2018.083
2. Mahajan R, Perera T, Elliott AD, et al. Subclinical device-detected atrial fibrillation and stroke risk: a systematic review and meta-analysis. Eur Heart J. 2018;39(16):1407-15.
3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-8.

This article originally appeared on The Cardiology Advisor