Meta-analysis of individual-patient data shows that elevated Lp(a) levels of 50 mg/dL or higher were associated with an increased hazard ratio of CV events, independent of other risk factors and statin or placebo treatment.
This is a summary of the presentation by John Kastelein, in which he discusses targeting PCSK9 in clinical practice, focusing on issues surrounding prescription of PCSK9 monoclonal antibodies.
In high Lp(a)-associated CV risk patients, reduction of Lp(a) with PCSK9 inhibition lowered this risk, even at very low LDL-c levels.
Trials on lowering Lp(a) have thusfar failed to show a CV outcome benefit. Brian Ference describes a more informative approach to look at Lp(a) data to identify who may benefit from Lp(a)-lowering therapy.
Elevated Lp(a) is now officially considered a genetically determined risk factor for CVD in the USA. Chapman summarizes how Lp(a) is atherogenic and how novel therapies may target this process.
In two prospective population cohorts, the increased CVD risk in individuals with high Lp(a) levels was reduced when LDL-c levels were <2.5 mmol/L.
Lp(a) concentrations have to be decreased by approximately 100 mg/dL in order to achieve clinically meaningful reductions in the risk of CHD, as shown by Mendelian randomization analysis.
VBWG at ACC 2018 Several novel targets have been discovered and new lipid-modifying therapies are being developed to prevent CVD, beyond LDL-c. Elliot Brinton discusses several of these, including omega-3 prescriptions, pemafibrate, apoC3, Lp(a), and shares the first trial results.
Inhibition of hepatic PCSK9 synthesis with the small interfering RNA inclisiran led to significant reductions of non-HDL-c and apoB, and increases of HDL-c, which were sustained up to day 180.
PCSK9 inhibition decreases the production and in combination with atorvastatin increases the clearance of Lp(a) particles, confirming a dual mechanism of action that lowers plasma Lp(a) concentration.
In a phase 2 study in patients with elevated Lp(a), measured LDL-c included circulating Lp(a)-c and lowering of Lp(a)-c led to lower LDL-c measurements and constant ‘true’ LDL-c levels.
In a sub-analysis of the ILLUMINATE study, PCSK9 and Lp(a) levels were dose-dependently increased by atorvastatin in patients at high CV risk.