Managing progressive ASCVD in patients with elevated Lp(a) despite optimal LDL-C control, review (Anatol J Cardiol 2026)

Lipoprotein(a) [Lp(a)] is a genetically determined, proatherogenic, and prothrombotic lipoprotein associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Elevated Lp(a) levels are associated with progressive ASCVD even when guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets are achieved under optimal lipid-lowering therapy. There is currently no approved pharmacological therapy specifically targeting Lp(a) reduction in routine clinical practice; therefore, current management strategies for patients with elevated Lp(a) primarily focus on aggressive control of modifiable cardiovascular risk factors and intensive LDL-C lowering. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provide a modest reduction in Lp(a) levels and have been associated with greater cardiovascular benefit in patients with high baseline Lp(a); however, this degree of reduction is often insufficient in individuals with markedly elevated Lp(a) levels and progressive ASCVD. At present, lipoprotein apheresis remains the only therapeutic option capable of achieving substantial and sustained reductions in Lp(a) concentrations and is recommended in selected high-risk patients with progressive ASCVD despite optimal medical therapy. Meanwhile, Lp(a)-specific therapies, including antisense oligonucleotides and small interfering RNA agents, are in advanced clinical development and have shown marked reductions in Lp(a) levels in early phase trials. These emerging therapies are expected to significantly change future treatment strategies for patients with Lp(a)-driven residual cardiovascular risk.