Impact of Aspirin on Primary Prevention of Cardiovascular Events in Patients with Elevated Lipoprotein(a): A Systematic Review and Meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis combining randomized and observational studies
PubMed 42018111 · doi:10.1007/s40256-026-00795-8
What was done
A systematic review and random-effects meta-analysis of MEDLINE, Web of Science, and CENTRAL (searched through November 2025) evaluated aspirin for primary cardiovascular prevention in individuals with elevated lipoprotein(a) (Lp(a) ≥ 50 mg/dL) or Lp(a)-associated genetic variants (e.g., rs3798220). Both randomized and observational studies were included. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included myocardial infarction (MI), coronary artery disease (CAD), cardiovascular mortality, and bleeding. Certainty was rated using GRADE.
What was found
Seven studies including 6,498 participants were analyzed: - MACE was not significantly reduced with aspirin (HR 0.99, 95% CI 0.79-1.24; I² = 23%; 4 studies). - MACE was significantly reduced in rs3798220-C carriers (HR 0.39, 95% CI 0.19-0.77; 2 studies). - Significant reductions occurred for MI (HR 0.60, 95% CI 0.41-0.88; 2 studies) and cardiovascular mortality (HR 0.48, 95% CI 0.28-0.83; 1 study). - 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 graded as very low.
Why it matters
Elevated Lp(a) is an independent cardiovascular risk factor lacking targeted preventive pharmacotherapy. These findings suggest unselected aspirin therapy does not reduce composite cardiovascular events in patients with elevated Lp(a), though genotype-guided use or specific MI risk reduction may warrant dedicated prospective trials.
Limits
The total sample size is small (6,498 participants across 7 studies), and the synthesis pools observational cohorts with randomized trials. Key secondary endpoints rely on very few studies (mortality from 1 study; MI and genetic carrier analyses from 2 studies). Residual confounding and wide confidence intervals led to an overall GRADE rating of very low certainty.
Cited by
- partial Taking baby aspirin has been shown to offer cardiovascular benefits in people who have elevated levels of lipoprotein(a).