The SPS3 RCT (Secondary Prevention of Small Subcortical Strokes) found no benefit from adding clopidogrel to aspirin compared with placebo in patients with a recent small vessel, lacunar stroke taking aspirin at the time of their index event. However, the median time from the qualifying event to enrollment in the SPS3 trial was >40 days, so results may have underestimated benefit in the early poststroke period.373 A recent meta-analysis of 5 studies, including 3 RCTs and 2 observational registries, of patients with noncardioembolic stroke taking aspirin at the time of the index event found a decreased risk of major cardiovascular events and recurrent stroke in patients switching to an alternative antiplatelet agent or combination antiplatelet therapy. This analysis included data from aspirin failure subgroups in the CHANCE trial of dual antiplatelet therapy in patients with minor stroke or TIA and the SOCRATES trial of aspirin versus ticagrelor. However, there was significant heterogeneity among the included studies, and results may have been driven by data from registries susceptible to unmeasured confounders and bias.374 See Tables LXXXVII and LXXXVIII in online Data Supplement 1. Anticoagulation might be considered in patients who are found to have abnormal findings on coagulation testing after an initial ischemic stroke, depending on the abnormality and the clinical circumstances. IIb C-LD Recommendation reworded for clarity from 2014 Secondary Prevention. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. For patients who have a noncardioembolic AIS while taking antiplatelet therapy, switching to warfarin is not indicated for secondary stroke prevention. III: No Benefit B-NR New recommendation. 