Physicians' Academy for Cardiovascular Education

PCSK9 inhibitors: From bench to bedside

Mar. 17, 2017 - Prof. Gilles Lambert – Sainte-Clotilde, France - ACC 2017, Washington DC, USA
Prof. Gilles Lambert describes the development since the discovery in 2002 of PCSK9 until the results of outcome trials with a PCSK9 inhibitor in 2017.

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.

PCSK9 inhibitor increases the removal of LDL and Lp(a) from the circulation via LDL-receptors

Feb. 7, 2017 - Reyes-Soffer G et al. - Circulation. 2017

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.

Agreement to licence two investigational lipid-lowering treatments

Jan. 12, 2017 - news

The agreement is for the development and commercialization of novel treatments for lowering lipoprotein(a) and apolipoprotein C-III

Novel therapy for the reduction of Lp(a) concentrations

Nov. 9, 2016 - Viney NJ, et al, The Lancet, 2016

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.

PCSK9 antibody therapy leads to effective and sustained LDL-c and Lp(a) decrease

Nov. 2, 2016 - Gaudet D, et al, Am J Cardiol, 2016

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). 

Elevated Lp(a) and PCSK9 levels associated with higher CAC in FH patients

Sep. 19, 2016 - Alonso R et al., Atherosclerosis 2016

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.

High Lp(a) confers greater risk for early ACS when LDL-C is elevated

Apr. 28, 2016 - Afshar M et al., J Am Heart Assoc. 2016

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.

Lp(a) cut-off values are applicable to calcific aortic valve disease in white and black individuals

Mar. 10, 2016 - Cao J, et al. Arterioscler Thromb Vasc Biol. 2016

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.

Treatment options to reduce CVD risk by lowering Lp(a) levels

Feb. 17, 2016 - Stein EA and Raal F., Cardiovasc Drugs Ther. 2016

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.

First potential drug to reduce Lp(a) concentrations to lower CV risk

Oct. 14, 2015 - Tsimikas S et al., Lancet 2015

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.

Limited use of Lp(a) as a prognostic marker in established CAD

Oct. 30, 2013 - O'Donoghue et al. JACC Oct 2013 - J Am Coll Cardiol. 2013 Oct 10

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.

Addition of niacin to statin therapy does not lower CVD event rate

Oct. 29, 2013 - Albers et al. JACC Oct 2013 - J Am Coll Cardiol. 2013 Oct 22;62(17):1575-9

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.