What is the clinical evidence from this study?

Study design: RCT. Population: Embolic stroke of undetermined source (ESUS) with patent foramen ovale (PFO) (n=7213). Intervention: Rivaroxaban vs. Aspirin 100 mg once daily. Primary outcome: Time to recurrent ischemic stroke (HR 0.54, 95% CI 0.22-1.36).

September 28, 2018ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam)180 citationsOpen Access

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

SKScott E. Kasner BSBalakumar Swaminathan PLPablo M. Lavados

Key Result

Among patients with ESUS and PFO, rivaroxaban did not significantly reduce the risk of recurrent ischemic stroke compared with aspirin (HR 0.54).

Study Design

Type

RCT (n=7,213)

Blinding

Double-blind

Randomization

1:1

Multicenter

Yes

Structured PICO

Does rivaroxaban reduce recurrent ischemic stroke compared with aspirin in patients with embolic stroke of undetermined source and patent foramen ovale?

Population

7,213 patients aged 50 and older with recent embolic stroke of undetermined source, including 534 with patent foramen ovale, followed for a mean of 11 months.

Intervention

Rivaroxaban 15 mg oral once daily (plus placebo-aspirin)

Comparator

Aspirin 100 mg oral once daily (plus placebo-rivaroxaban)

Outcome

Time to recurrent ischemic strokehard clinical

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.

Main Result

Hazard Ratio: 0.54 (95% CI 0.22–1.36)

Absolute Event Rate: 2.6% vs 4.8%

Limitations

Early termination of the trial reduced statistical power
PFO was likely underdetected because bubble studies were not mandated
Non-standardized approach to PFO diagnosis
Underestimated the prevalence of PFO because a standardized approach (e.g., bubble study) was not required
Early termination of the trial dramatically truncated the planned period of follow-up and yielded a lower number of events than anticipated, reducing power to only 51%
Statistical tests for interactions typically offer limited power
Meta-analysis included only 3 trials over a 20-year span with relatively few events

Abstract

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.

Ask AI

Helpful

Bookmark

View Full Paper