Although the trials of antiplatelet monotherapy in patients with AF were underpowered to precisely estimate the risk of nonfatal major extracranial bleeding, trials of aspirin for the primary and secondary prevention of cardiovascular disease have conclusively demon- strated that aspirin is associated with an increased risk of major hemorrhage. An individual patient data meta-analysis combining data from six cardiovas- cular primary prevention trials (95,000 subjects) and a meta-analysis of 60 cardiovascular secondary pre- vention trials (94,000 subjects) found that aspirin is associated with a signi cant 50% to 60% relative increase, respectively, in the risk of major extracra- nial bleeding.67,68 For the outcomes of death and systemic embolism, pooled estimates of treatment effect from trials of antiplatelet monotherapy in patients with AF were imprecise, leaving uncer- tainty about the impact of antiplatelet monotherapy on these outcomes when compared with no treat- ment (Table 4). 2.1.3 VKAs vs Antiplatelet Monotherapy (Aspirin): The evidence summarized in sections 2.1.1 and e542S Antithrombotic Therapy for Atrial Fibrillation (Continued) Table [Section Should Antiplatelet (Aspirin) Monotherapy Rather Than No Therapy Be Used in Patients With AF? a,b Quality Assessment Summary of Findings No. 