Impact of Aspirin on Primary Prevention of Cardiovascular Events in Patients with Elevated Lipoprotein(a): A Systematic Review and Meta-analysis

INTRODUCTION: Elevated lipoprotein(a) (Lp(a)) and Lp(a)-raising genetic variants (e.g. rs3798220) are independent cardiovascular risk factors lacking preventive strategies. Given the prothrombotic properties attributed to high Lp(a), aspirin was hypothesized to confer benefit in primary prevention. We performed a systematic review and meta-analysis to evaluate the impact of aspirin on cardiovascular and bleeding outcomes in this population. METHODS: MEDLINE, Web of Science and CENTRAL were searched (November 2025) for randomized and observational studies assessing aspirin use in primary prevention among individuals with Lp(a) ≥ 50 mg/dL or Lp(a)-associated genetic variants. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included myocardial infarction (MI), coronary artery disease (CAD), cardiovascular mortality, and bleeding. Random-effects meta-analyses pooled the Hazard ratios (HR) with 95% confidence intervals (CI). Certainty of evidence was assessed using GRADE. RESULTS: = 23%; four studies). MACE reduction was associated with aspirin in rs3798220-C carriers (HR 0.39, 95% CI 0.19-0.77, two studies). Aspirin was also associated with significant reduction of events regarding MI (HR 0.60, 95% CI 0.41-0.88, two studies) and cardiovascular mortality (HR 0.48, 95% CI 0.28-0.83, one study), whereas CAD was not significantly reduced (HR 0.82, 95% CI 0.59-1.12). Bleeding risk was numerically higher but not statistically significant (HR 1.13, 95% CI 0.89-1.44). Overall certainty of evidence was very low. CONCLUSIONS: Aspirin was not associated with a reduction of MACE among individuals with elevated Lp(a). A potential benefit for MI requires confirmation in adequately designed and powered prospective studies. Pooled data from rs3798220-C carriers suggest a potential significant benefit that warrants further investigation REGISTRATION: PROSPERO identifier no. CRD42024520731.