2.1.2 Antiplatelet Monotherapy (Aspirin) vs No Therapy: Several RCTs of antiplatelet monotherapy vs no therapy in patients with AF have shown that antiplatelet therapy leads to, at best, a modest reduc- tion in the risk of nonfatal stroke. Antiplatelet mono- therapy in these trials was either with aspirin alone (AFASAK 1; SPAF I; EAFT; United Kingdom Tran- sient Ischaemic Attack Aspirin trial [UK-TIA]; Low- Dose Aspirin, Stroke, Atrial Fibrillation [LASAF]; European Stroke Prevention Study [ESPS]-2; and Japan Atrial Fibrillation Stroke Trial [JAST]), aspirin in combination with xed (ineffective) minidose warfarin (Swedish Atrial Fibrillation Trial [SAFT]), or dipyridamole (ESPS-2).55,58,60,62-66 Aspirin dosing in these trials typically ranged from 50 to 325 mg/d. In the LASAF, JAST, and SAFT trials, aspirin was compared with a no-treatment control arm, whereas in the remaining trials, comparison was to placebo.63,64,66 ESPS-2 and UK-TIA were stroke prevention trials conducted primarily in non-AF populations, and only the data from the subset of patients with AF are con- Pooled data from these trials provide moderate- quality evidence (rated down for imprecision) that antiplatelet monotherapy is associated with a 21% relative reduction in risk of nonfatal stroke com- pared with no treatment (Table 4). Although our con- dence in the bene ts of aspirin therapy is moderate, our con dence in its bleeding risk is high. 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. 