Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Background: Ischaemic stroke may occur despite antiplatelet therapy (APT). We aimed to investigate frequency, potential causes and outcomes in patients with ischaemic stroke despite APT. Methods: In this cohort study, we enrolled patients with imaging-confirmed ischaemic stroke from the Swiss Stroke Registry (01/2014-07/2022). We determined the frequency of prior APT, assessed stroke aetiology (modified TOAST classification) and determined the association of prior APT with unfavourable functional outcome (modified Rankin Scale score 3-6) and recurrent ischaemic stroke at 3months using regression models. Results: Among 53,352 patients, 27,484 (51.5%) had no prior antithrombotic treatment, 17,760 (33.3%) were on APT, 7039 (13.2%) on anticoagulation and 1069 (2.0%) were on APT+anticoagulation. In patients with a history of ischaemic stroke/TIA (n=11,948; 22.4%), 2401 (20.1%) had no prior antithrombotic therapy, 6594 (55.2%) were on APT, 2489 (20.8%) on anticoagulation and 464 (3.9%) on APT+anticoagulation. Amongst patients with ischaemic stroke despite APT, aetiology was large artery atherosclerosis in 19.8% (n=3416), cardiac embolism in 23.6% (n=4059), small vessel disease in 11.7% (n=2011), other causes in 7.4% (n=1267), more than one cause in 6.3% (n=1078) and unknown cause in 31.3% (n=5388). Prior APT was not independently associated with unfavourable outcome (aOR=1.06; 95% CI: 0.98-1.14; p=0.135) or death (aOR=1.10; 95% CI: 0.99-1.21; p=0.059) at 3-months but with increased odds of recurrent stroke (6.0% vs 4.3%; aOR 1.26; 95% CI: 1.11-1.44; p<0.001). Conclusions: One-third of ischaemic strokes occurred despite APT and 20% of patients with a history of ischaemic stroke had no antithrombotic therapy when having stroke recurrence. Aetiology of breakthrough strokes despite APT is heterogeneous and these patients are at increased risk of recurrent stroke.