Current perspectives on Lp(a)-lowering therapies: Who may benefit?

Increasing evidence has implicated lipoprotein(a) [Lp(a)] in the pathogenesis of atherosclerosis and calcific aortic valve disease. There are currently no therapies available in clinical practice that selectively lower Lp(a) levels. In the current state, the presence of an elevated Lp(a) level plays an important role in risk enhancement and triaging patients to the use of more intensive targeting of established cardiovascular risk factors. A number of therapies are currently in clinical development with the potential to reduce formation of Lp(a) particles. This includes antisense oligonucleotides and short interfering RNA agents that inhibit hepatic apolipoprotein(a) synthesis and oral small molecule inhibitors that inhibit binding of apolipoprotein(a) and apolipoprotein B. Early clinical studies have demonstrated the ability of these agents to effectively reduce Lp(a) levels by more than 80%, and they are well tolerated by patients. A number of these agents are currently being evaluated in large clinical trials to determine their impact on cardiovascular events. The evolution of this field and implications for the clinical approach to the prevention of cardiovascular disease will be reviewed.