Among patients with ESUS and PFO, rivaroxaban did not significantly reduce the risk of recurrent ischemic stroke compared with aspirin (HR 0.54).
RCT (n=7,213)
Double-blind
1:1
Yes
Does rivaroxaban reduce recurrent ischemic stroke compared with aspirin in patients with embolic stroke of undetermined source and patent foramen ovale?
In patients with ESUS and PFO, anticoagulation may reduce the risk of recurrent stroke compared to antiplatelet therapy, though the trial was underpowered due to early termination.
Hazard Ratio: 0.54 (95% CI 0.22–1.36)
Absolute Event Rate: 2.6% vs 4.8%
BACKGROUND: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS: =0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. INTERPRETATION: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. FUNDING: Bayer and Janssen.
Kasner et al. (2018) conducted an RCT in Embolic stroke of undetermined source (ESUS) with patent foramen ovale (PFO) (n=7,213). Rivaroxaban vs. Aspirin 100 mg once daily was evaluated on Time to recurrent ischemic stroke (HR 0.54, 95% CI 0.22-1.36). Among patients with ESUS and PFO, rivaroxaban did not significantly reduce the risk of recurrent ischemic stroke compared with aspirin (HR 0.54).