Efficacy and safety of aspirin for primary prevention in adults with elevated lipoprotein(a) or genetic susceptibility via LPA gene variants: a systematic review and meta-analysis.
Level 2 - randomized trial
Systematic review including both randomized trial data and observational studies
PubMed 42138694 · doi:10.1093/eurjpc/zwag207
What was done
Authors performed a systematic review and meta-analysis across PubMed/MEDLINE, Embase, and Cochrane Central following PRISMA and Cochrane guidelines. They assessed adults without established atherosclerotic cardiovascular disease with elevated Lp(a) (50 mg/dL or greater), high-risk LPA genotypes, or elevated genetic risk scores comparing aspirin versus no aspirin use. Random-effects meta-analyses using restricted maximum-likelihood estimation with Hartung-Knapp-Sidik-Jonkman adjustment pooled hazard ratios (HR) and 95% confidence intervals (CI) for major adverse cardiovascular events (MACE) and clinical bleeding.
What was found
Across six studies including 6,628 participants, aspirin was not associated with a statistically significant reduction in MACE (HR = 0.60; 95% CI 0.31-1.17; P = 0.1) or clinical bleeding events (HR = 1.24; 95% CI 0.83-1.87; P = 0.18). Subgroup analyses showed a non-significant reduction in MACE for elevated Lp(a) (HR = 0.63; 95% CI 0.16-2.49; P = 0.284) and a statistically significant reduction in LPA rs3798220 carriers (HR = 0.37; 95% CI 0.19-0.71; P = 0.003), but this genetic subgroup finding was inconsistent across sensitivity analyses.
Why it matters
High Lp(a) or high-risk LPA genotype alone does not currently warrant routine primary-prevention aspirin, as evidence fails to establish a clear cardiovascular benefit over potential bleeding risks.
Limits
The meta-analysis included only six studies with a modest total sample size (n = 6,628) and pooled both trials and lower-quality observational designs. Findings for rs3798220 carriers were unstable across sensitivity analyses and susceptible to small-sample bias, while study-level variation in aspirin dosing and bleeding definitions introduced heterogeneity.
Cited by
- contradicts Taking baby aspirin has been shown to offer cardiovascular benefits in people who have elevated levels of lipoprotein(a).