Abstract A003: Baseline Systolic Blood Pressure Modifies the Net Benefit of Combination Antithrombotic Therapy After Ischemic Stroke/TIA in Patients With NVAF and ASCVD: Subanalysis of the ATIS–NVAF trial

Background: The optimal antithrombotic strategy after ischemic stroke or TIA in patients with nonvalvular atrial fibrillation (NVAF) and atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We tested whether baseline systolic blood pressure (SBP) modifies the net clinical effect of intensified therapy. Methods: The ATIS–NVAF trial randomized patients with ischemic stroke/TIA, NVAF, and ASCVD to oral anticoagulant (OAC) monotherapy or OAC plus single antiplatelet therapy. In this subanalysis of participants with baseline SBP data, patients were stratified by SBP <130 (low SBP) vs ≥130 mmHg (high SBP). The primary endpoint was a composite of ischemic events (stroke, myocardial infarction, systemic embolism, or cardiovascular death) and major bleeding. Secondary endpoints included all–cause mortality, any ischemic events, and recurrent ischemic stroke. Safety endpoints included major bleeding and major or clinically relevant non-major (CRNM) bleeding. Cox models estimated adjusted hazard ratios (HRs) within strata and tested treatment–by–SBP interaction. Results: Of the 314 patients (median age: 78 years; 225 men), 116 were in the low SBP stratum and 198 were in the high SBP stratum. The adjusted HRs of the combination therapy compared to the monotherapy for the incidence of primary outcome were 0.34 (95 % confidence interval [CI]: 0.12–0.96) for the low SBP stratum and 1.70 (95 % CI: 0.82–3.55) for the high SBP stratum (interaction p = 0.018). As for secondary endpoints, any ischemic events (interaction p = 0.065) and recurrent ischemic stroke (interaction p = 0.073) favored combination therapy in the low–SBP stratum. No significant interaction was observed for major bleeding (interaction p = 0.120); however, in the high–SBP stratum, combination therapy increased major/CRNM bleeding (HR 2.91, 95% CI 1.15–7.33). Kaplan–Meier curves mirrored these findings. Conclusions: Baseline SBP appears to modify the benefit–risk profile of combination antithrombotic therapy in post–stroke/TIA patients with NVAF and ASCVD. In those with SBP <130 mmHg, combination therapy reduced ischemic events without excess major bleeding, supporting SBP-guided individualization of antithrombotic therapy.