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.
In young asymptomatic individuals with family history of premature ASCVD, elevated Lp(a) is related to higher CAC score, resulting in the identification of individuals with subclinical atherosclerosis.
In type 2 diabetic patients with mixed dyslipidemia on maximal statin therapy, the addition of the PCSK9 inhibitor alirocumab is more effective than usual care.
Prof. John Kastelein describes 3 major disturbances in lipoprotein metabolism contributing to CV risk. Novel therapies are being developed to address residual risk after LDL-c eradication.
In a prospective community-based cohort, Lp(a) ≥50 mg/dL was associated with higher stroke risk in those without AF, but not in those with AF, nor with an elevated risk of AF.
In the CPGS study, OxPL-apoB and OxPL-apo(a) were genetically and observationally associated with CAVD risk and closely correlated with Lp(a) levels.
VBWG ACC 2017 Sotirios Tsimikas summarises the rationale of innovative therapeutic approaches targeting Lp(a), ApoC3 or ATP citric lyase and in what stage of clinical testing they currently are.
PCSK9 Expert Opinions Prof. Gilles Lambert describes the development of PCSK9 inhibitors since the discovery in 2002 of PCSK9 as a circulating protein targeting the LDL receptor for degradation. Now in 2017, results of outcome trials with a PCSK9 inhibitor are available.