Rivaroxaban Shows Superiority to Aspirin in Lowering Risk of Recurrent Stroke in Patients With Left Ventricular Dysfunction

Data from the phase 3 NAVIGATE ESUS trial indicate that rivaroxaban (Xarelto; Janssen) is superior to aspirin in decreasing the risk of recurrent stroke or systemic embolism in patients with left ventricular (LV) dysfunction.

The study, published in JAMA Neurology, evaluated 7213 patients with neuroimaging-confirmed embolic strokes of undetermined source between 7 days and 6 months prior to screening. Among these patients, 7107 (98.5%) had a documented assessment of LV function and were included in the exploratory analysis.

Patients were randomized to either 15 mg of rivaroxaban or 100 mg of aspirin once daily for the prevention of recurrent stroke. Of the 7107 participants with a documented assessment of LV function, 502 (7%) had LV dysfunction reported.

Over a median follow-up of 10.4 months, the primary outcome of recurrent stroke or systemic embolism was found in 321 patients (4.9% per year). Event rates were 2.4% per year (95% CI, 1.1-5.4) in the rivaroxaban cohort compared with 6.5% (95% CI, 4.0-11) in the aspirin cohort.

Among patients who did not have LV dysfunction (n = 6605), event rates were similar between both cohorts. Event rates in the rivaroxaban cohort were 5.3% per year (95% CI, 4.5-6.2) compared with 4.5% per year on aspirin (95% CI, 3.8-5.3). After adjusting for the main effects of assigned treatment and LV dysfunction, the observed heterogeneity of treatment effect was deemed statistically significant (P = .03 for interaction).

Further, patients with LV dysfunction administered rivaroxaban showed a significantly lower risk of the primary outcome (HR, 0.36 [95% CI, 0.14-0.93]). Conversely, patients without LV dysfunction had a similar risk (HR, 1.16 [95% CI, 0.93-1.46]).

Secondary outcomes included recurrent stroke, systemic embolism, myocardial infarction, and cardiovascular mortality. These events were reported in 390 of the 7107 patients (overall, 5.5%), of whom 201 (6.1% per year) patients were in the rivaroxaban group compared with 189 (5.7% per year) in the aspirin cohort.

Among 502 patients with LV dysfunction, rates were 4.9% per year (95% CI, 2.8-8.6) in the rivaroxaban cohort vs 9.5% per year (95% CI, 6.3-14) in the aspirin cohort. The study authors suggested a dedicated secondary stroke prevention trial among these patients to evaluate the efficacy and safety of anticoagulation in preventing cardiac embolism and subsequent stroke.

A major bleeding event was reported in 83 participants out of the total patient population. Approximately 95% (n = 78) of these adverse events (AEs) occurred in patients without evidence of LV dysfunction, (rivaroxaban: n = 55; aspirin: n = 23) and the remaining 5 AEs were reported in participants with evidence of LV dysfunction (rivaroxaban: n = 5; aspirin: n = 0).

REFERENCE

Merkler AE, Pearce LA, Kasner SE, et al. Left ventricular dysfunction among patients with embolic stroke of undetermined source and the effect of rivaroxaban vs aspirin: a subgroup analysis of the NAVIGATE ESUS randomized clinical trial. JAMA Neurol. Published online October 25, 2021. doi:10.1001/jamaneurol.2021.3828