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Lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 inhibitors


Julius, U; Tselmin, S; Schatz, U; Fischer, S; Bornstein, S R (2019). Lipoprotein(a) and proprotein convertase subtilisin/kexin type 9 inhibitors. Clinical Research in Cardiology Supplements, 14(S1):45-50.

Abstract

Lipoprotein(a) (Lp(a)) is an internationally accepted independent atherogenic risk factor. Details about its synthesis, many aspects of composition and clearance from the bloodstream are still unknown. LDL receptor (LDLR) (and probably other receptors) play a role in the elimination of Lp(a) particles. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors increase the number of available LDLRs and in this way very effectively reduce the LDL cholesterol (LDL-C) concentrations. As shown in controlled studies using PCSK9 inhibitors, Lp(a) levels are decreased by 20 to 30%, though in some patients no effect was observed. So far, it has not been clarified whether this decrease is associated with an effect on the incidence of cardiovascular events (CVEs). In two recently published well-performed secondary prevention studies (FOURIER with evolocumab, ODYSSEY OUTCOMES with alirocumab) baseline Lp(a) levels were shown to have an impact on CVEs independently of baseline LDL-C concentrations. The rather modest PCSK9 inhibitor-induced decrease of Lp(a) was associated with a reduction of CVEs in both studies, even after adjusting (ODYSSEY OUTCOMES) for demographic variables (age, sex, race, region), baseline Lp(a), baseline LDL-C, change in LDL-C, and clinical variables (time from acute coronary syndrome, body mass index, diabetes, smoking history). The largest decrease of CVEs was seen in patients with relatively low concentrations of both LDL-C and Lp(a) (FOURIER). These findings will probably have an influence on the use of PCSK9 inhibitors in patients with high Lp(a) concentrations.

Abstract

Lipoprotein(a) (Lp(a)) is an internationally accepted independent atherogenic risk factor. Details about its synthesis, many aspects of composition and clearance from the bloodstream are still unknown. LDL receptor (LDLR) (and probably other receptors) play a role in the elimination of Lp(a) particles. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors increase the number of available LDLRs and in this way very effectively reduce the LDL cholesterol (LDL-C) concentrations. As shown in controlled studies using PCSK9 inhibitors, Lp(a) levels are decreased by 20 to 30%, though in some patients no effect was observed. So far, it has not been clarified whether this decrease is associated with an effect on the incidence of cardiovascular events (CVEs). In two recently published well-performed secondary prevention studies (FOURIER with evolocumab, ODYSSEY OUTCOMES with alirocumab) baseline Lp(a) levels were shown to have an impact on CVEs independently of baseline LDL-C concentrations. The rather modest PCSK9 inhibitor-induced decrease of Lp(a) was associated with a reduction of CVEs in both studies, even after adjusting (ODYSSEY OUTCOMES) for demographic variables (age, sex, race, region), baseline Lp(a), baseline LDL-C, change in LDL-C, and clinical variables (time from acute coronary syndrome, body mass index, diabetes, smoking history). The largest decrease of CVEs was seen in patients with relatively low concentrations of both LDL-C and Lp(a) (FOURIER). These findings will probably have an influence on the use of PCSK9 inhibitors in patients with high Lp(a) concentrations.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 April 2019
Deposited On:21 Mar 2019 14:48
Last Modified:25 Sep 2019 00:30
Publisher:Springer
ISSN:1861-0706
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1007/s11789-019-00099-z
PubMed ID:30838555

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