Aspirin in Primary Prevention of CVD: A Pragmatic Outline and Advice for Treatment Personalization

Cardiovascular disease (CVD) remains the leading global cause of morbidity and mortality. While low-dose aspirin is well established for secondary prevention, its role in primary prevention is controversial because modest benefits in cardiovascular benefits must be balanced against increased bleeding risk, as highlighted by recent large trials. Current guidelines recommend restricting aspirin use to individuals at higher cardiovascular risk without elevated bleeding risk, yet significant heterogeneity persists in defining these thresholds. Evidence from randomized trials, guidelines, cohort and modeling analyses, and post hoc or observational subgroup studies suggests that selected patients with advanced subclinical atherosclerosis or specific high-risk markers may have a more favorable risk-benefit profile, although the certainty and directness of evidence vary across subgroups. This narrative review and pragmatic clinical guide presents an illustrative tiered framework based on clinical, imaging, and biomarker markers-such as coronary artery calcium score, carotid plaque score, and lipoprotein(a)-to support individualized discussion of preventive aspirin therapy. The framework is not a validated risk calculator or standalone treatment algorithm, and decisions should balance absolute cardiovascular risk, major bleeding risk, evidence certainty, and patient preferences.