TY - JOUR
T1 - Lipoprotein(a) and PCSK9 inhibition
T2 - Clinical evidence
AU - Ruscica, Massimiliano
AU - Greco, Maria Francesca
AU - Ferri, Nicola
AU - Corsini, Alberto
N1 - Publisher Copyright:
© The Author(s) 2020.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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).
AB - 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).
KW - FOURIER
KW - Lipoprotein(a)
KW - ODYSSEY OUTCOMES
KW - PCSK9
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U2 - 10.1093/EURHEARTJ/SUAA135
DO - 10.1093/EURHEARTJ/SUAA135
M3 - Article
AN - SCOPUS:85098725149
VL - 22
SP - L53-L56
JO - European Heart Journal, Supplement
JF - European Heart Journal, Supplement
SN - 1520-765X
ER -