Role of aspirin in the primary prevention of cardiovascular disease in patients with hyperlipoproteinaemia(a)

Abstract

Lipoprotein(a) [Lp(a)] is a well-established cardiovascular disease (CVD) risk factor with elevated Lp(a) levels contributing to a higher incidence of atherosclerotic CVD (ASCVD). However, no Lp(a)-specific interventions are currently available in the primary CVD prevention in individuals with elevated Lp(a) levels. RNA-based therapies targeting Lp(a) are under investigation in phase III clinical trials. However, these trials are mostly focused on the secondary prevention of patients with established ASCVD. Aspirin (ASA) has demonstrated efficacy in reducing major adverse cardiovascular events in secondary prevention; however, its role in primary prevention is limited due to an increased risk of haemorrhagic events. Consequently, current guidelines recommend ASA for primary prevention only in patients with a high risk for CVD and low haemorrhagic risk. Identifying sub-populations that may benefit from ASA in primary prevention is an ongoing research focus. To that effect, some evidence suggests that individuals without established ASCVD but with elevated Lp(a) levels may represent such a sub-group, where the potential cardiovascular benefits of ASA may outweigh the risk of bleeding. However, though promising, these data are limited, largely retrospective and require further validation. The mechanisms through which ASA may confer benefit in this population have not been fully elucidated but potential pathways include a modest reduction in Lp(a) levels and the inhibition of Lp(a)- mediated platelet activation and aggregation. Whilst preliminary findings are promising, there are still significant gaps in the literature, underscoring the need for more rigorous, prospective studies to elucidate the role of ASA in this specific context.