Impact of cancer on outcomes following breakthrough ischaemic stroke on oral anticoagulants for atrial fibrillation: insights from the ASPERA-R study

BACKGROUND: Breakthrough ischaemic stroke during oral anticoagulation (OAC) for atrial fibrillation (AF) represents a major therapeutic challenge, especially in patients with cancer, who face competing risks of thrombosis and bleeding. This study investigated the impact of cancer on 90-day outcomes after ischaemic stroke on OAC. PATIENTS AND METHODS: We analysed patients with AF who experienced ischaemic stroke while on continuous OAC enrolled in the international retrospective ASPERA-R study, comprising 35 stroke centres across 9 countries. Inverse probability weighting was applied to adjust for baseline imbalances, and weighted Cox, ordinal logistic and generalised linear models were used to estimate adjusted 90-day risks for the primary (ischaemic stroke or TIA), secondary (mRS shift, vascular/all-cause death) and safety (moderate-to-severe bleeding, ICH, 24-h haemorrhagic transformation) outcomes. RESULTS: Among 1649 included patients (mean age 78.0 ± 10.7 years; 45.8% male), 247 (15.0%) had cancer, of whom 87 (35.2%) had active cancer and 160 (64.8%) were in remission. After weighting, patients with cancer had a significantly higher 90-day risk of new ischaemic stroke or TIA (8.2% vs 2.8%; adjusted hazard ratio [aHR] 2.56; 95% CI, 1.59-4.13; P < .001) and worse 90-day mRS score distribution (adjusted odds ratio 1.29; 95% CI, 1.08-1.54; P = .005) than those without cancer. Active cancer conferred a > 4-fold higher risk of new ischaemic stroke or TIA (HR 4.48, 95% CI, 2.46-8.13; P < .001) and nearly 3-fold higher risk of moderate-to-severe bleeding (HR 2.77; 95% CI, 1.30-5.88; P = .008). Patients with cancer in remission showed increased ischaemic risk (HR 2.60; 95% CI, 1.59-5.25; P = .001) but not bleeding risk. Haematological malignancies carried a higher risk for both new ischaemic stroke or TIA (HR 3.06; 95% CI, 1.69-5.54; P = .001) and moderate-to-severe bleeding (HR 3.47, 95% CI, 1.57-7.70; P = .006) compared to solid malignancies. CONCLUSION: Cancer, particularly active and haematological malignancies, substantially worsens 90-day prognosis after breakthrough stroke on OAC, underscoring the need for refined risk stratification and tailored secondary prevention. TRIAL REGISTRATION: URL: www.clinicaltrials.gov; Unique identifier: NCT06823466.