Key result
Adding antiplatelets to OAC increases bleeding risk without reducing recurrent ischemic stroke in AF.
Why the study?
The benefit-risk balance of adding antiplatelet therapy to oral anticoagulation in patients with atherothrombotic brain infarction and concomitant nonvalvular atrial fibrillation is unclear.
Does adding antiplatelet therapy to oral anticoagulation reduce recurrent ischemic stroke in patients with nonvalvular atrial fibrillation and atherosclerotic cardiovascular disease after atherothrombotic or cardioembolic stroke?
Does adding antiplatelet therapy to oral anticoagulation reduce recurrent ischemic stroke in patients with nonvalvular atrial fibrillation and atherosclerotic cardiovascular disease after atherothrombotic or cardioembolic stroke?
In patients with NVAF and atherothrombotic stroke, adding antiplatelet therapy to oral anticoagulation increases bleeding risk without significantly reducing recurrent ischemic stroke.
May warrant avoiding antiplatelet addition to anticoagulation in NVAF with atherothrombotic stroke; challenges consensus favoring dual therapy.
Background: Antiplatelet therapy is recommended for prevention of recurrent stroke in patients with atherothrombotic brain infarction (ATBI). However, the benefit-risk balance of adding antiplatelet therapy to oral anticoagulant (OAC) in patients with concomitant nonvalvular atrial fibrillation (NVAF) is unclear. We compared ischemic and bleeding outcomes of OAC plus antiplatelet versus OAC alone in ATBI and cardioembolic stroke (CE) in patients with NVAF and atherosclerotic cardiovascular disease (ASCVD). Methods: ATIS-NVAF was a randomized trial of patients with NVAF and ASCVD after ischemic stroke or transient ischemic attack assigning OAC alone or OAC plus antiplatelet therapy. In this post-hoc analysis, we included those with a final etiologic diagnosis of ATBI or CE. The primary outcome was recurrent ischemic stroke. Secondary outcomes were major or clinically relevant non-major bleeding and all-cause mortality. Results: A total of 175 patients were included (ATBI: n=82, CE: n=93). In the ATBI group, recurrent ischemic stroke occurred in 14.8 % in the combination arm and 19.1% in the monotherapy arm (HR, 0.74; 95% CI, 0.23–2.33; p=0.61). In the CE group, recurrent ischemic stroke occurred in 13% in the combination arm and 7.9% in the monotherapy arm (HR, 1.63; 95% CI, 0.36–7.27; p=0.53). In ATBI patients, hemorrhagic events tended to be more frequent in the combination arm than in the monotherapy arm (25.4% vs 8.7%); the Cox model showed a trend toward higher risk (HR, 3.36; 95% CI, 0.91 –12.4; p=0.07). All-cause mortality did not differ significantly between groups. Conclusions: In patients with ATBI and NVAF, adding antiplatelet therapy to OAC increased bleeding without evidence of reduced recurrent ischemic stroke or mortality. These findings do not support routine combination therapy for secondary prevention in this subgroup
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Shirakawa et al. (2026) studied this question. In patients with atherothrombotic stroke and nonvalvular atrial fibrillation, adding antiplatelet therapy to anticoagulation increased bleeding risk without reducing recurrent ischemic stroke.
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