Which Cryptogenic Stroke Patients Benefit From Anticoagulation?

April 16, 2019

Rivaroxaban appears to modestly reduce recurrent stroke in a small subgroup of patients with embolic stroke of undetermined source (ESUS) and moderate to severe left atrial enlargement, a subgroup analysis of the NAVIGATE-ESUS trial shows.

The subgroup analysis was published online in JAMA Neurology on April 8. It was previously presented at the 11th World Stroke Congress (WSC) 2018.

"In patients with cryptogenic stroke — which we now refer to as embolic stroke of undetermined source — around one third have subclinical atrial fibrillation (AF)," lead author Jeff Healey, MD, McMaster University, Hamilton, Ontario, Canada, explained to Medscape Medical News.

"We know anticoagulants reduce future stroke risk in patients with AF but trying to identify patients with subclinical AF is difficult," he said.

The NAVIGATE-ESUS trial looked at the strategy of treating all patients with cryptogenic stroke with rivaroxaban but results were neutral in terms of stroke reduction and there with an increased rate of bleeding, "so this is not an effective approach," he said. "This subgroup analysis was done to investigate whether we can identify a group of patients who are at increased risk of AF in whom rivaroxaban had a benefit."

In the NAVIGATE-ESUS trial, 7000 patients were stratified by predictors of AF, including left atrial diameter, frequency of premature atrial contractions, and HAVOC score, a validated score derived from seven common clinical patient characteristics associated with risk of future AF.

For the current analysis, researchers investigated whether these predictors could be used to identify a group of patients in whom rivaroxaban reduces recurrent stroke risk.

Results showed the mean HAVOC score was 2.6, mean left atrial diameter was 3.8 cm, and median daily frequency of premature atrial contractions was 48.

Although higher HAVOC scores and increased frequency of premature atrial contractions did identify patients at greater risk of AF, neither of these measures affected the association of rivaroxaban with recurrent ischemic stroke (P for interaction = .67 and .96, respectively).

Increased left atrial diameter was also associated with increased risk of AF, and among the predefined subgroup of patients with a left atrial diameter of more than 4.6 cm (9% of the overall population), the risk of ischemic stroke was lower among the rivaroxaban group compared with the aspirin group (1.7% vs 6.5% per year; hazard ratio, 0.26; P for interaction = .02).

"ESUS is a broad catch-all and includes a variety of strokes which we think have embolic causes," Healey said. "In this subgroup analysis we have identified one group of these patients who may benefit from anticoagulation. These results need to be confirmed in another randomized trial and such a trial — ARCADIA — is now underway."

"So I would say that this current subgroup analysis has found an interesting observation that needs confirmation," he concluded. "These results won't change clinical practice in any great way, yet they may cause us to now look harder for AF in our patients with left atrium enlargement. This could involve more intensive AF surveillance possibly with an implantable cardiac monitor."

The study was supported by Bayer and Janssen Research. Healey has reported receiving grants from Bayer during the conduct of the study.

JAMA Neurol. Published online April 8, 2019. Abstract

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