Project
RESPECT ESUS: Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate (110 mg or 150 mg, oral b.i.d.) versus acetylsalicylic acid (100 mg oral q.d.) in patients with Embolic Stroke of undetermined Source
Automatically Closed · 2016 until 2018
Kägi Georg, Vehoff Jochen, Müller Anna, Mbialeu Suzie
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Brief description/objective
There is uncertainty over the optimal stroke prevention treatment for patients with ESUS. The current treatment recommendations of ASA alone, sometimes given with clopidogrel or ticlopidine (P08-06684, P08-08481) are based on limited data.
There is some evidence from subanalyses of secondary stroke prevention trials that the use of anticoagulants (such as warfarin) may provide benefits over antiplatelets after strokes with a clear embolic pattern, although a prospective randomized trial in this specific patient population has not yet been conducted. The only randomized evaluation of anticoagulation in cryptogenic stroke is the subgroup analysis of the Warfarin-Aspirin Recurrent Stroke Study (WARSS)
In a subset of patients from this study, the primary outcome (two-year rate of recurrent ischemic stroke or death) was halved in those assigned to warfarin (9% warfarin vs. 17% acetylsalicylic acid) despite the low achieved intensity of warfarin anticoagulation. The WARSS subgroup data support the hypothesis that anticoagulation may be more efficacious than acetylsalicylic acid for patients with cryptogenic ischemic stroke when those with lacunar stroke topography are excluded.
A randomized trial comparing an oral anticoagulant with antiplatelet therapy for secondary prevention among ESUS patients is warranted and justified by the effectiveness of warfarin for stroke prevention in patients with major-risk cardioembolic sources such as AF, subgroup analyses from prior warfarin trials, and the introduction of safer and more effective novel anticoagulants.
The NOAC DE is highly effective against embolic stroke in AF and has an excellent safety profile with a low risk of intracranial hemorrhage (U09-3249-02). Dabigatran etexilate is likely to reduce stroke recurrence in ESUS compared with ASA and to be associated with an acceptably low rate of major hemorrhage. The current trial intends to deliver evidence of the effectiveness and safety of DE in ESUS patients with the goal of expanding the market authorization of dabigatran etexilate and improving patient care.