3-Year Follow-Up of STROKE-AF Demonstrates Stroke Risk Increase With Atrial Fibrillation

Findings from the STROKE-AF trial (NCT02700945) showed that after 3 years of observation, approximately 1 in 5 patients with ischemic stroke had atrial fibrillation (AF) observed by an insertable cardiac monitor (ICM), a 10-fold increase versus standard of care (SOC).¹ These findings suggest undetected AF may increase risk for cardioembolic stroke for a patient population not considered normally for AF management.

At 12-months, an AF incidence rate of 12.1% was observed in patients monitored with an ICM vs. 1.8% with SOC, which was similar to the results in the CRYSTAL AF study (NCT00924638) of cryptogenic stroke patients.² Results from STROKE-AF were presented as a late breaker by lead author Lee Schwamm, MD, professor of neurology at Harvard Medical School, at the 2023 International Stroke Conference (ISC), February 8-10, in Dallas, Texas.

“We know that about 25% of ischemic strokes happen in patients who have survived a previous stroke. This drives our quest to understand not just the cause of the most recent stroke, but also their risk for future strokes due to all treatable causes, so we can do our best to prevent the next one,” Schwamm said in a statement.³

The prospective, randomized, controlled, multicenter trial compared AF incidence rates detected with ICM (n = 242) versus SOC (n = 250) in patients with ischemic stroke, attributed to large or small vessel disease, and no AF diagnosis prior. Patients were aged more than or 60 years old of age, with a stroke index of less than or 10 days prior to ICM, and no indication of longterm oral anticoagulation.

“We found that the rate of atrial fibrillation continued to increase over the course of the three years, therefore, it’s not just a short-lived event and self-resolving related to the initial stroke,” Schwamm noted in a statement.³ “Fibrillation is common in these patients. Relying on routine monitoring strategies is not sufficient and neither is placing a 30-day continuous monitor on the patient. Even if fibrillation is ruled out in the first 30 days, most of the cases are missed — because, as we found, more than 80% of the episodes are first detected more than 30 days after the stroke.”

At 3-years, AF incidence rate was 21.7% in the ICM arm vs 2.4% SOC arm (HR,10.0; 95% CI, 4.0-25.2; P <.001) per Kaplan-Meier estimates. The median duration of the longest AF episode was 10.0 (IQR, 4.0-192.0) min among patients with ICM and AF. Notably, 37.2% of patients had an episode lasting more than or 1 hour. The median maximum daily AF burden in patients with AF was 0.3 hours, with 1 in every 4 patients having AF longer than 5.3 hours. No significant difference in the rates of recurrent stroke were observed at 3 years between the ICM and SOC arms (17.0% vs 14.1%; HR, 1.10; 95% CI, 0.67-1.78; P = .71).

“There is still a lot that we don’t yet understand about why people who have had a previous stroke have another one; however, this study contributes important information to one potential cause— namely, unsuspected atrial fibrillation—for some of those 25% of patients with recurrent strokes,” Schwamm added in a statement.³ “What we need to sort out is what additional risk does atrial fibrillation add, and can the use of anticoagulation reduce that risk, especially for the type of major and disabling strokes that are often associated with atrial fibrillation.”

Previous coverage on the trial identified several risk factors associated with poststroke AF, the most significant being congestive heart failure (CHF) and left atrial fibrillation (LAE).⁴ The analysis included 242 participants randomly assigned to the ICM from the trial, 27 (11.6%) of which had AF detected at 12-month follow-up. A multivariable analysis showed that only CHF (HR, 5.06; 95% Ci, 1.45-17.64; P = .05) and LAE (HR, 3.32; 95% CI, 1.34-8.19; P = .009) were associated with an increased likelihood of detecting AF during monitoring, with a trend toward significance for QRS duration (HR, 1.02; 95% CI, 1.00-1.04; P = .06).

Click here for more coverage of ISC 2023.

REFERENCES
1. Schwamm LH, Kamel H, Sethi PP, et al. 3-year Results from the STROKE-AF Randomized Trial. Presented at: 2023 International Stroke Conference; February 8-10; Dallas, TX. LB1
2. Sinha AM, Diener HC, Morillo CA, et al. Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF): design and rationale. Am Heart J. 2010;160(1):36-41.e1. doi:10.1016/j.ahj.2010.03.032
3. Irregular heart rhythms detected in 1 in 5 stroke survivors, increasing risk of new stroke. News Release. American Heart Association. Published February 8, 2023. Accessed February 8, 2023. https://newsroom.heart.org/news/irregular-heart-rhythms-detected-in-1-in-5-stroke-survivors-increasing-risk-of-new-stroke
4. Schwamm LH, Kamel H, Granger CB, et al. Predictors of atrial fibrillation in patients with stroke attributed to large- or small-vessel disease: a prespecified secondary analysis of the STROKE AF randomized clinical trial. JAMA Neurol. Published online November 14, 2022. doi:10.1001/jamaneurol.2022.4038