Increasing evidence has implicated lipoprotein(a) [Lp(a)] in the causality of atherosclerosis and calcific aortic stenosis. This has stimulated immense interest in developing novel approaches to integrating Lp(a) into the setting of cardiovascular prevention. Current guidelines advocate universal measurement of Lp(a) levels, with the potential to influence cardiovascular risk assessment and triage of higher-risk patients to use of more intensive preventive therapies. In parallel, considerable activity has been undertaken to develop novel therapeutics with the potential to achieve selective and substantial reductions in Lp(a) levels. Early studies of antisense oligonucleotides (e.g., mipomersen, pelacarsen), RNA interference (e.g., olpasiran, zerlasiran, lepodisiran) and small molecule inhibitors (e.g., muvalaplin) have demonstrated effective Lp(a) lowering and good tolerability. These agents are moving forward in clinical development, in order to determine whether Lp(a) lowering reduces cardiovascular risk. The results of these studies have the potential to transform our approach to the prevention of cardiovascular disease.
Keyphrases
- ejection fraction
- small molecule
- aortic stenosis
- cardiovascular disease
- risk assessment
- human health
- emergency department
- transcatheter aortic valve replacement
- end stage renal disease
- aortic valve replacement
- aortic valve
- transcatheter aortic valve implantation
- type diabetes
- randomized controlled trial
- nucleic acid
- coronary artery disease
- prognostic factors
- clinical trial
- case control
- heavy metals
- climate change