Key result
Aspirin use did not significantly reduce major adverse cardiovascular events (HR 0.60; 95% CI 0.31-1.17; P=0.1) in adults without ASCVD but with elevated Lp(a) or high-risk LPA genotypes.
Why the study?
Routine aspirin for primary prevention has modest cardiovascular benefit and increased bleeding risk in average-risk adults, but whether individuals with elevated Lp(a) or high-risk LPA variants derive greater benefit remains uncertain.
Does aspirin reduce major adverse cardiovascular events in adults without ASCVD but with elevated Lp(a) or high-risk LPA genotypes?
Meta-Analysis (n=6,628)
Does aspirin reduce major adverse cardiovascular events in adults without ASCVD but with elevated Lp(a) or high-risk LPA genotypes?
In adults without ASCVD but with elevated Lp(a) or high-risk LPA genotypes, aspirin for primary prevention did not significantly reduce cardiovascular events and was associated with numerically higher bleeding risk.
Aims Routine aspirin use for primary prevention yields modest cardiovascular benefit but increases bleeding risk in average-risk adults. Whether individuals with elevated lipoprotein(a) [Lp(a)] levels or high-risk LPA variants derive greater benefit remains uncertain. Methods and results Following Cochrane and PRISMA guidelines, we systematically searched PubMed/MEDLINE, Embase, and Cochrane Central for studies of adults without ASCVD, elevated Lp(a) (≥50 mg/dL), high-risk LPA genotypes, or elevated genetic risk scores, comparing aspirin vs. no aspirin use. Random-effects meta-analyses using restricted maximum-likelihood (REML) estimation with Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment were used to pool hazard ratios (HR) and 95% confidence intervals (CI). In six studies, 6628 participants were included. Pooled random effects showed no significant reduction in major adverse cardiovascular events (MACE) with aspirin (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 nonsignificant reduction MACE among elevated Lp(a) (HR = 0.63; 95% CI 0.16 to 2.49; P = 0.284) and statistically significant reduction among LPA rs3798220 carriers (HR = 0.37; 95% CI 0.19 to 0.71; P = 0.003), though this finding was not consistent in the sensitivity analyses. Conclusion Among adults without ASCVD but with elevated Lp(a) or high-risk LPA genotypes, aspirin use did not confer a statistically significant cardiovascular benefit and was associated with numerically higher bleeding risk. The apparent reduction seen in rs3798220 carriers was inconsistent and likely reflects small-sample bias.
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Lopes et al. (2026) conducted a meta-analysis in Primary prevention in adults with elevated Lp(a) or genetic susceptibility (n=6,628). Aspirin vs. No aspirin use was evaluated on Major adverse cardiovascular events (MACE) (HR 0.60, 95% CI 0.31-1.17, p=0.1). Aspirin use did not significantly reduce major adverse cardiovascular events (HR 0.60; 95% CI 0.31-1.17; P=0.1) in adults without ASCVD but with elevated Lp(a) or high-risk LPA genotypes.
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