This uncertainty is re- flected in international guidelines, where, for example, aspirin is not recommended in European guidelines for primary ASCVD preventionS4.6-13 but is recommended in prior US guidelines for selected primary prevention for adults who have elevated risk of ASCVD based on tradi- tional risk factors.S4.6-14,S4.6-15 Adding to this controversy are more recently conducted primary-prevention trials that, in contrast to older trials,S4.6-12 have shown less overall benefit of prophylactic aspirin alongside coad- ministration of contemporary ASCVD preventive treat- ments, such as evidence-based hypertension and cho- Recommendation-Specific Supportive Text 1. To balance the benefits and risks, prior US guide- lines have recommended prophylactic aspirin only in the setting of elevated ASCVD risk (eg, as calculated by risk estimators like the PCE or based on the presence of specific ASCVD risk Meta-regression analyses of his- torical trials show that observed ASCVD risk tracks reasonably well with baseline-estimated ASCVD In contrast, observed bleeding risk on aspirin is less well correlated with baseline-esti- mated ASCVD risk.S4.6-19 (A nonexhaustive list of scenarios associated with increased risk of bleed- ing includes: a history of previous gastrointestinal bleeding or peptic ulcer disease or bleeding from other sites, age >70 years, thrombocytopenia, coagulopathy, CKD, and concurrent use of other medications that increase bleeding risk, such as nonsteroidal anti-inflammatory drugs, steroids, direct oral anticoagulants, and warfarin.) 