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.
Alirocumab treatment of healthy volunteers reduced LDL-C and LDL-apoB concentrations and doubled the efficiency with which LDL particles were removed from the circulation.
The agreement is for the development and commercialization of novel treatments for lowering lipoprotein(a) and apolipoprotein C-III
Novel antisense oligonucleotides therapy IONIS-APO(a)-L Rx (phase I/II study) results in even more Lp(a) reduction than with IONIS-APO(a) Rx / ISIS-APO(a) Rx therapy.
The consistent reductions in Lp(a) suggest that PCSK9 inhibition with alirocumab, not only effectively lowers LDL-c but also has a substantial and sustained effect on Lp(a).
In asymptomatic FH patients on stable chronic lipid-lowering therapy, elevated Lp(a) levels and elevated PCSK9 levels were associated with higher coronary artery calcification.
In young ACS patients, high Lp(a) is strongly associated with high LDL-C, thus individuals with high Lp(a) and LDL-C >3.5 mmol/L may benefit from LDL-lowering therapy.
In a large multiethnic cohort, significant associations between Lp(a) levels and subclinical CAVD were observed in black and white individuals, but not in Hispanic and Chinese Americans.
Lp(a) levels are largely genetically determined, and hardly affected by lifestyle factors. This is an inventory of therapeutic options that may reduce levels of this CVD risk factor.
An antisense oligonucleotide directed at hepatic apo(a) mRNA, selectively and potently reduced levels of plasma Lp(a) and its associated oxidised phospholipid, in phase I trial.
Although increased risk of MACE was seen at high Lp(a) levels, marked heterogeneity is seen across studies. Especially if LDL-c is well-controlled, value of Lp(a) is limited.
AIM-HIGH: although the addition of extended release niacin to LDL-lowering therapy has favourable effects on lipoproteins, it does not yield a reduction of CV events.