STROKE AF at 3 Years: High AF Rate After Atherosclerotic Stroke

February 09, 2023

In the STROKE AF study, among patients who had had a stroke that was presumably caused by atherosclerosis, the rate of atrial fibrillation (AF) was almost 22% at 3 years, as detected by continuous monitoring.

Three-year results from the study were presented by Lee H. Schwamm, MD, Massachusetts General Hospital, Boston, at the International Stroke Conference (ISC) 2023, being held in Dallas, Texas.

Schwamm said the high rate of AF detection in this study suggests that continuous monitoring for AF should be considered for a larger population of stroke patients, rather than just those with cryptogenic stroke.

"We found a much higher rate of AF than we expected in this population of patients who have had an atherosclerotic stroke," Schwamm told | Medscape Cardiology.

"These AF occurrences were found by a device, so they are known as 'device-documented AF.' The patient is not generally aware of symptoms, but 67% of the AF episodes lasted for more than 1 hour, showing that this is not trivial AF. This is meaningful AF," he said.

Schwamm said the major question is whether these cases of AF that are detected with a device warrant treatment with anticoagulation. He noted that in this study, clinicians decided to provide anticoagulation to 70% to 80% of patients in whom AF was detected.

"If we think it deserves treatment, then we have to look for it. And if we care about finding AF, we have no choice but to monitor continuously," he said.

"If this data doesn't convince you that AF is present in this population, I don't think any data will. Because it is consistent, it accumulates over time and looks remarkably similar to a set of data that we have all become very comfortable with ― the CRYSTAL- AF study in patients with cryptogenic stroke," he stated.

Schwamm noted that the STROKE AF trial was not based on the cause of the index stroke; rather, it was asking whether there are risk factors that could contribute to the 25% stroke recurrence rate in this population that are not covered in current guidelines.

"I'm really trying to move away from the anchor that I was trained in, which is to figure out the cause of the last stroke to help decide how to prevent the next stroke, towards more of a probabilistic model ― of what is all the information I have at my disposal and how do I act on it to prevent the next stroke? We have to start thinking differently about building models for future stroke risk and determining therapy based on that," he commented.

Changing Practice

ISC 2023 program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, New Jersey, and moderator of the session at which the results were presented, discussed the STROKE-AF results in a highlights presentation.

"To me as clinician, these results are even more relevant than those at 12 months," Jovin said. "The lesson I took is that AF is even more prevalent than we thought. The burden of AF is significant in these patients, and it doesn't seem to be limited to a particular time. These are very thought-provoking results which are going to change clinical practice. I think the threshold for long-term monitoring will be lower."

Co-moderator Lauren Sansing, MD, Yale University School of Medicine, added: "This study shows that the longer we monitor, the more patients with AF we are likely to pick up. And because in two thirds of patients with AF, it lasted longer than 1 hour, I do believe this was clinically relevant AF. The question now is, do we monitor everyone? I think it puts the burden on us to search for AF in our patients."

In his presentation, Schwamm explained that on the basis of the CRYSTAL-AF study, insertable cardiac monitoring devices are frequently used to identify post-stroke AF in patients with cryptogenic stroke. In the device-monitored arm of that study, AF was detected in 12.4% of patients over 12 months, vs 2.0% in the control arm.

"However, we don't know how often AF is detected in other presumed stroke types ― largely those due to atherosclerosis."

He pointed out that at present, long-term monitoring post stroke for the detection of AF is not currently recommended for patients with ischemic stroke, owing to presumed small-vessel occlusion or large-artery atherosclerosis.

"In these patients, we are not suspecting AF because we believe the cause of the stroke was not embolic. But we wanted to investigate what the AF risk is in these patients, who often have multiple stroke risk factors," he said.

The trial enrolled 496 patients at 33 centers in the US. Eligible patients were aged 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor and had had an index stroke that was attributed to large-artery or small-vessel disease. Patients were randomly assigned either to continuous monitoring with the Reveal LINQ device (Medtronic) or to the control arm following site-specific standard of care for AF detection.

Schwamm noted that usual care for these patients normally involves monitoring for just a few days while in hospital, but this picks up less than 5% of AF occurrences.

Baseline characteristics of patients in the STROKE AF study showed that the enrolled population was at high risk for stroke, with a CHADSVASC score 5. But the index strokes were generally small; the median National Institutes of Health Stroke Scale (NIHSS) score was 2.

Results at 12 months, reported 2 years ago, showed a 12.5% incidence of AF with continuous monitoring, vs 1.8% with standard of care (HR, 7.7; P < .001), rates similar to that found in the CRYSTAL-AF study.

By 3 years, the rate of detected AF had risen to 21.7% in the continuous monitoring arm, vs 2.4% in the control arm (HR, 10.0; P < .001).

"At 12 months, we were seven times more likely to detect AF with continuous monitoring in these patients, and by 3 years, it was 10 times more likely that AF would be detected with continuous monitoring. I think we've settled the question of the best way to find AF in these patients ― it is with an inserted device," Schwamm said.

"We have also shown that this is not a transient rise in AF after the stroke which then diminishes over the next few years. It is a continuous and progressive detection of AF."

Schwamm pointed out that 88% of the recorded AF episodes were asymptomatic. "So relying on patients self-reporting symptoms when deciding who to monitor is unreliable and not a sensible strategy."

The median time to the first adjudicated AF episode at 12-month follow-up was 99 days; at the 3-year follow-up, it was 284 days.

"This shows that 30 days of monitoring with an external patch is not sufficient to exclude the presence of AF. And this really argues for a strategy of immediate insertion of cardiac monitor placement if your goal is to look for AF," Schwamm commented.

Is This Clinically Relevant AF?

Schwamm acknowledged that there is a question of whether device-detected AF should be thought about in the same way as clinically detected AF with respect to future stroke risk.

He noted that in this study, 67.4% of patients for whom AF was detected by continuous monitoring (31 of 46 patients) had at least one episode of AF that lasted more than 1 hour.

"This is not a trivial little squiggle of something on an EKG which then goes away. This is of significant duration that the cardiologist who adjudicated these rhythm strips felt confident was AF."

He added: "AF lasting more than 1 hour crosses the threshold for most practitioners I know to feel confident in treating the patient with anticoagulation. If it was symptomatic AF, this wouldn't even be a question."

Schwamm made the point that device-detected AF has been accepted as worthy of treatment in patients after cryptogenic stroke.

"If we are honest with ourselves and if we have no hesitation in starting anticoagulation in a patient with cryptogenic stroke who has had device-detected AF 6 months later, should we decide that if the patient has had a lacunar stroke, we can ignore that same device-detected fibrillation?"

He put forward the idea that, at some level, all stroke is cryptogenic. "We never know for sure what the cause was. We have hypotheses, we have associations, but we don't really know. So how much should we weigh that presumptive etiology in terms of how we interpret a rhythm disturbance of fibrillation?"

When looking for predictors of AF in this study, the investigators found that patients were more likely to have an episode of AF detected if they had one of the four following risk factors: congestive heart failure, left atrial enlargement, obesity, or QRS prolongation.

"In patients with any one of those four factors, 30% of those had device-detected AF. These are same predictors of AF that we are all accustomed to," Schwamm said.

Shared Decision-Making

Schwamm told | Medscape Cardiology that in his practice, for these patients, the decision as to whether to use continuous monitoring is made with the patient through shared decision-making.

"We discuss the chance that they could have AF, and I suggest that it might be worth looking for it, but there are factors to be considered. There is a cost to the device, and reimbursement may depend on insurance coverage. Also, some patients may have strong feelings about having the chip implanted in their body."

He says implanting the chip is easy. "It takes longer to check in at the front desk than to put the device in. It is injected under the skin. It just needs two stitches and a Band-Aid." The device connects with a smartphone, and the results are interpreted by a cardiologist.

Schwamm pointed out that the optimal antithrombotic regimen for these patients in whom AF is detected remains uncertain and should be the focus of future research.

"Do we just stick to antiplatelet therapy or advance to anticoagulation? In moving to an anticoagulant, are we providing less effective prevention for the atherosclerotic stroke risk at the expense of reducing the AF-related stroke risk? That may be a reasonable trade-off because we know the disability from AF-associated stroke is much higher.

"Or perhaps the optimal therapy is aspirin plus low-dose anticoagulant? Or left atrial appendage closure and an antiplatelet for patients at a higher risk of bleeding?" he said. "These are the really important questions we need to start asking."

He added that he hopes a future study will address these questions, but he noted that it would have to be a large study, that it would have to first identify these patients and then randomly assign them to anticoagulation or to no treatment. "That is quite a major undertaking."

In the highlights presentation, Jovin said he was uncertain of which of these patients in whom AF is detected would benefit from anticoagulation. He said he would also like to see a randomized trial on this. But he added: "This would be challenging, as there is the issue of whether there would be equipoise to allow us to randomize to a placebo."

Sansing agreed. "I think it would be a hard sell. I would have to think carefully about randomizing a patient to anticoagulation therapy or no therapy who has been found to have AF."

Schwamm noted that the current STROKE-AF study was not designed or powered to detect differences in stroke recurrence rates and that there was no difference in stroke recurrence rates between the two arms. There was also no randomization with regard to treatment; choice of medication was left to the discretion of the treating physician.

But he noted that for only 3 of the 34 patients with recurrent stroke in the continuous-monitor arm was AF detected prior to the recurrent stroke, and only one of those three was receiving anticoagulation at the time of the recurrent stroke.

"These strokes were occurring in patients who did not have device-detected AF," Schwamm said. "This is because the population in this study were loaded with stroke risk factors and are at risk of recurrent stroke, but we don't have the opportunity in this study to really understand the significance of the recurrent strokes."

The STROKE AF trial was funded by Medtronic. Schwamm is a consultant to Medtronic.

International Stroke Conference (ISC) 2023: Presentation LB1. Presented February 8, 2023.

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