News, literature and expert perspectives on PCSK9 inhibition in lipid management
The European Commission (EC) has approved the use of evolocumab in patients with established atherosclerotic CVD (MI, stroke, PAD) to reduce CV risk.
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.
New ORION-data shows inclisiran has a one-size-fits-all dosing regimen of 300 mg on day 1, day 90 and every six months thereafter, across a wide range of dyslipidemia patients, including HoFH.
A model assuming 100% adherence to maximal statin dose showed that only 10% of heFH patients with CHD would reach guideline-recommended LDL-c goal, and about half of those without CHD.
The potential incremental benefit of PCSK9 inhibition varies a lot among patients with stable CAD, with the greatest benefit observed in younger patients with highest risk factor burden and high LCL-c levels.
Patients with a history of MI who are closer to their most recent event, have had multiple prior MIs or have residual multi-vessel CAD, had higher CV risk reductions with evolocumab.
Atherogenic dyslipidemia increases CV risk in diabetes patients. Prof. Ray discusses the importance of dyslipidemia in these patients, the associated CV risk and new medical therapies to reduce this risk.
A clinically meaningful LDL-c-lowering activity was observed in patients receiving alirocumab who are double or compound heterozygous, or homozygous for genes that are causative for FH.
Treatment with bempedoic acid lowers LDL-c by an additional 30% when added to evolocumab treatment in patients with hypercholesterolemia.
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.
Following the results from the FOURIER trial, EMA’s CHMP has issued a positive opinion for the PCSK9 inhibitor evolocumab to reduce CV risk in patients with established ASCVD.