Compelling evidence has emerged from epidemiological and Mendelian randomization analyses relative to the causality of lipoprotein(a) [Lp(a)] in atherosclerotic cardiovascular diseases (ASCVD), being elevated Lp(a) a strong risk factor regardless of the reduction of LDL-C achieved by statins. So far, no specific available agent can lower Lp(a) to the extent required to achieve a cardiovascular (CV) benefit, i.e. approximately 100 mg/dL. The most recent outcomes trial FOURIER with evolocumab showed that a 25 nmol/L (12 mg/dL) reduction in Lp(a) corresponded to a 15% decrement in the relative risk of cardiovascular disease. The ODYSSEY OUTCOMES trial with alirocumab has been the first demonstrating that a reduction in Lp(a) associates with less major adverse cardiovascular events (MACE), i.e. hazard ratio: 0.994 per 1 mg/dL decrement in Lp(a). The Lp(a) lowering effect driven by PCSK9 inhibition was confirmed in carriers of PCSK9 loss-of-function mutations in which Lp(a) and oxPL-apoB levels were decreased compared to non-carriers as was for a slight larger number of apo(a) Kringle IV repeats. Although PCSK9 inhibitors are not able to decrease Lp(a) to the extent required to achieve a CV benefit, their use has led to a higher discontinuation rate in lipoprotein apheresis in patients with progressive ASCVD and high plasma Lp(a).
Lipoprotein(a) and PCSK9 inhibition: clinical evidence / M. Ruscica, M.F. Greco, N. Ferri, A. Corsini. - In: EUROPEAN HEART JOURNAL SUPPLEMENTS. - ISSN 1520-765X. - 22:Supplement L(2020 Nov 18), pp. L53-L56.
|Titolo:||Lipoprotein(a) and PCSK9 inhibition: clinical evidence|
RUSCICA, MASSIMILIANO (Primo) [Writing – Original Draft Preparation]
Greco, Maria Francesca (Secondo) [Writing – Original Draft Preparation]
CORSINI, ALBERTO (Ultimo) [Writing – Original Draft Preparation] (Corresponding)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||18-nov-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/eurheartj/suaa135|
|Appare nelle tipologie:||01 - Articolo su periodico|