Aspirin and Elevated Lp(a) in Primary Prevention

Key Takeaways

• Overall pooled data did not suggest lower MACE with aspirin in the broader elevated-Lp(a) primary-prevention population.
• Lower pooled estimates were observed for myocardial infarction and cardiovascular mortality, while coronary artery disease was not significantly reduced.
• Among rs3798220-C carriers, a lower MACE estimate was reported, bleeding was numerically higher without statistical significance, and overall evidence certainty was very low.

Could aspirin alter primary-prevention risk in people with elevated lipoprotein(a) or Lp(a)-associated variants? A systematic review and meta-analysis found no overall reduction in major adverse cardiovascular events, with a pooled hazard ratio of 0.99 and 95% CI 0.79-1.24. The analysis focused on aspirin use before established cardiovascular disease in biomarker-defined and genotype-defined primary-prevention groups. Elevated Lp(a) of at least 50 mg/dL and Lp(a)-raising variants defined the core populations under study. In the overall elevated-Lp(a) population, pooled results did not indicate lower MACE with aspirin.

The review examined aspirin for primary prevention in individuals with Lp(a) at or above 50 mg/dL or with Lp(a)-associated genetic variants. Investigators searched MEDLINE, Web of Science, and CENTRAL through November 2025. Included studies were randomized or observational and compared aspirin exposure with non-aspirin or control conditions. Major adverse cardiovascular events were the primary outcome, while myocardial infarction, coronary artery disease, cardiovascular mortality, and bleeding were secondary outcomes. Random-effects models pooled hazard ratios with 95% confidence intervals, certainty was graded with GRADE, and the protocol was registered in PROSPERO as CRD42024520731.

Across secondary efficacy outcomes, myocardial infarction had a lower pooled estimate with aspirin, at HR 0.60 and 95% CI 0.41-0.88 across two studies. Cardiovascular mortality also had a lower pooled estimate, with HR 0.48 and 95% CI 0.28-0.83 in one study. Coronary artery disease was not significantly reduced, with HR 0.82 and 95% CI 0.59-1.12. Four studies contributed to the primary MACE analysis, and heterogeneity was relatively low at I2 = 23%. The overall MACE result remained unchanged, while several narrower endpoints showed lower pooled estimates.

Among rs3798220-C carriers, aspirin was associated with a lower MACE estimate of HR 0.39 and 95% CI 0.19-0.77 across two studies. Bleeding was numerically higher but not statistically significant, at HR 1.13 and 95% CI 0.89-1.44. The investigators rated the overall certainty of evidence as very low. Overall, aspirin was not associated with lower MACE among individuals with elevated Lp(a). The authors added that the myocardial infarction signal requires confirmation in adequately designed and powered prospective studies, and that the rs3798220-C finding warrants further investigation.