Xarelto outperforms aspirin in reducing recurrent stroke risk

Xarelto was superior to aspirin for lowering the risk for recurrent stroke or systemic embolism among individuals with left ventricular dysfunction, according to results of a post hoc exploratory analysis of a randomized clinical trial.

“A subset of cryptogenic strokes often appear to be embolic and are referred to as embolic strokes of undetermined source (ESUS),” Alexander E. Merkler, MD, MS, of the department of neurology at Weill Cornell Medical College in New York, and colleagues wrote in JAMA Neurology. “Two recent randomized clinical trials (the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism

in ESUS [NAVIGATE ESUS] trial and the Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source [RESPECT-ESUS] trial) found that anticoagulation was no better than aspirin at reducing the risk of recurrent stroke and systemic embolism among all patients with ESUS.

“However, patients included in these trials had heterogeneous potential etiologies of ESUS, and anticoagulation was not an effective overarching treatment strategy for this undifferentiated population,” they added.

According to the researchers, sources of cardiac embolism and subsequent stroke can arise from the left ventricle (LV), and LV regional wall motion abnormalities and impaired LV contractility are common among patients with ESUS and can also lead to thrombus formation, cardiac embolism and stroke. However, these forms of LV dysfunction are not currently thought of as linked to increased risk for cardiac embolism, thus leading to a lack of anticoagulation prescriptions among patients with stroke who have these abnormalities.

In the current analysis of data from NAVIGATE ESUS, Merkler and colleagues examined whether anticoagulation was superior to aspirin for recurrent stroke reduction among patients with ESUS and LV dysfunction. They analyzed data from 459 stroke recruitment centers across 31 countries of 7,107 patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening and who had a documented assessment of LV function at study entry. Researchers randomly assigned participants to 15 mg of Xarelto (rivaroxaban, Janssen/Bayer) or 100 mg of aspirin once per day. Main outcomes included determining whether rivaroxaban outperformed aspirin in reducing the risk for recurrent stroke or systemic embolism (primary outcome) and recurrent stroke, systemic embolic, myocardial infarction or cardiovascular mortality (secondary outcome). Researchers identified LV dysfunction locally via echocardiography, and they defined it as “moderate to severe global impairment in LV contractility and/or a regional wall motion abnormalities.”

Further, they used a Cox proportional hazards model to assess for treatment interaction and to calculate the HRs for those randomly assigned to rivaroxaban compared with aspirin by LV dysfunction status.

Results showed LV dysfunction among 502 (7.1%) participants (mean age, 67 years; 26% women). The researchers noted annualized primary event rates in these patients of 2.4% (95% CI, 1.1-5.4) for those treated with rivaroxaban and 6.5% (95% CI, 4-11) for those who received aspirin. Participants without LV dysfunction had similar rates for rivaroxaban (5.3%; 95% CI, 4.5-6.2) and aspirin (4.5%; 95% CI, 3.8-5.3). Those with LV dysfunction who received rivaroxaban compared with aspirin had a lower risk for the primary outcome (HR = 0.36; 95% CI, 0.14-0.93), unlike participants without LV dysfunction (HR = 1.16; 95% CI, 0.93-1.46). The researchers noted similar results for the secondary outcome.

“A dedicated secondary stroke prevention trial in patients with LV dysfunction should be considered to evaluate the efficacy and safety of anticoagulation to prevent cardiac embolism and subsequent stroke,” Merkler and colleagues wrote.