Aspirin for the primary prevention of major adverse cardiovascular events in patients with elevated lipoprotein(a): a meta-analysis

Abstract Background Lipoprotein(a) Lp(a), an emerging biomarker with pro-atherogenic properties, may help identify individuals at higher risk of major adverse cardiovascular events (MACE). Elevated Lp(a) levels and genotypes associated with elevated Lp(a) are established predictors of future MACE. However, the optimal approach for primary prevention in this population remains unclear. Purpose We conducted a systematic review and meta-analysis to assess the role of aspirin in the primary prevention of MACE in patients with elevated Lp(a) or elevated Lp(a) genotypes. Methods We searched three electronic databases from inception to Dec 31, 2024, to identify randomized controlled trials (RCTs) or observational studies assessing the effectiveness of aspirin on the primary prevention for major adverse cardiovascular events (MACE) in individuals with elevated Lp(a) concentration or genotypes associated with elevated Lp(a). The primary outcome is MACE, defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The secondary safety outcome was major bleeding. Random-effects meta-analysis was conducted with restricted maximum likelihood method as a between-study estimator. Results We identified 2 post-hoc analysis of RCT and 3 prospective studies including a total of 49,871 patients (Aspirin = 22,001; Placebo = 27,870) between 1988 to 2014. The study follow-up period ranged from a median of 4.7 to 26 years. Two studies investigated patients with elevated serum Lp(a) (≥50 mg/dL), and the other three studies assessed rs-3798220-C status carriers, a genotype associated with elevated Lp(a) (Table 1). Aspirin use was associated with a significantly lower hazard of MACE in patients with elevated serum Lp(a) (HR 0.51; 95% CI 0.35 to 0.75, I2 = 0%; Figure 1A) and rs-3798220-C status carriers (HR 0.59; 95% CI 0.36 to 0.98, I2 = 0%; Figure 1A). There was no significant difference in the risk of bleeding between the two groups (HR 1.24; 95% CI 0.89 to 1.72, I2 = 0%; Figure 1B). Conclusion Aspirin use is associated with a reduced risk of MACE in individuals with elevated Lp(a) levels or rs3798220-C genotype, without a significant increase in bleeding risk. These findings suggest that aspirin may be a beneficial primary prevention strategy in this high-risk population.Baseline Characteristics of studies Clinical endpoints