NAVIGATE
Trial question
What is the role of rivaroxaban in secondary stroke prevention in patients with embolic stroke of undetermined source?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
38.4% female
61.6% male
N = 7213
7213 patients (2777 female, 4432 male)
Inclusion criteria: patients with embolic stroke of undetermined source; with patent foramen ovale and without PFO
Key exclusion criteria: a history of AF, severely disabling stroke, the presence of or plan to insert an implantable ECG loop recorder, specific indication for chronic anticoagulation or for chronic antiplatelet therapy, or previous non-traumatic ICH
Interventions
N=3609 rivaroxaban (15 mg tablet plus placebo-aspirin once daily)
N=3604 aspirin (at a dose of 100 mg tablet plus placebo-rivaroxaban once daily)
Primary outcome
Incidence of recurrent ischemic stroke in patients with patent foramen ovale
2.6
4.8
4.8/100 py
3.6/100 py
2.4/100 py
1.2/100 py
0.0/100 py
Rivaroxaban
Aspirin
No significant
difference ↔
No significant difference in the incidence of recurrent ischemic stroke in patients with patent foramen ovale (2.6/100 py vs. 4.8/100 py; HR 0.54, 95% CI 0.22 to 1.36)
Secondary outcomes
No significant difference in the incidence of recurrent ischemic stroke in patients without PFO (4.9/100 py vs. 4.6/100 py; HR 1.06, 95% CI 0.84 to 1.33)
Safety outcomes
No significant differences in risks of major bleeding in patients with PFO (HR 2.05, 95% CI 0.51-8.18) and without PFO (HR 2.82, 95% CI 1.69-4.70; p interaction=0.68).
Conclusion
In patients with embolic stroke of undetermined source; with patent foramen ovale and without PFO, rivaroxaban was not superior to aspirin with respect to the incidence of recurrent ischemic stroke in patients with patent foramen ovale.
Reference
Kasner SE, Swaminathan B, Lavados P et al. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial. Lancet Neurol. 2018 Dec;17(12):1053-1060.
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