Lipoprotein(a) and PCSK9 inhibition: clinical evidence

Ruscica, Massimiliano; Greco, Maria Francesca; Ferri, Nicola; Corsini, Alberto

doi:10.1093/eurheartj/suaa135

Cited by 25 publications

(20 citation statements)

References 20 publications

(23 reference statements)

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“…Proprotein convertase subtilisin/Kexin type 9 (PCSK9), an enzyme that is formed in the liver, has been described as a central player in cholesterol metabolism, particularly because PCSK9 stimulates the degradation of the LDL receptor and then leads to an increase in circulating LDL [ 75 ]. Inhibition of PCSK9 and its associated drastic reduction in circulating LDL suggests a promising treatment for patients with cardiovascular diseases [ 76 , 77 ]. In addition to lowering LDL, PCSK9 inhibitors were associated with a 15 to 30% reduction in Lp(a) plasma levels, which may benefit CAVD patients.…”

Section: The Effect Of Lipid-lowering Therapy In Aortic Stenosismentioning

confidence: 99%

Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?

Nsaibia

Devendran

Goubaa

et al. 2022

JCM

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Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stimulate endothelial dysfunction and promote inflammation. Inflammation and growth factors actively promote the synthesis of the extracellular matrix (ECM) and trigger an osteogenic program. The accumulation of ECM proteins promotes lipid adhesion to valve tissue, which could initiate the osteogenic program in interstitial valve cells. Statin treatment has been shown to have the ability to diminish the death rate in subjects with atherosclerotic impediments by decreasing the serum LDL cholesterol levels. However, the use of HMG-CoA inhibitors (statins) as cholesterol-lowering therapy did not significantly reduce the progression or the severity of aortic valve calcification. However, new clinical trials targeting Lp(a) or PCSK9 are showing promising results in reducing the severity of aortic stenosis. In this review, we discuss the implication of lipids in aortic valve calcification and the current findings on the effect of lipid-lowering therapy in aortic stenosis.

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Section: The Effect Of Lipid-lowering Therapy In Aortic Stenosismentioning

confidence: 99%

Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?

Nsaibia

Devendran

Goubaa

et al. 2022

JCM

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“…Available lipid-lowering therapies have little value for Lp(a) reduction. Aside from statins that could raise Lp(a) blood concentrations [68,69], PCSK9 inhibitors reduce Lp(a) levels by 25-30% [70] and there is evidence that reduction of Lp(a) elicited by these drugs might contribute to an improved prognosis in coronary disease patients [71]. Finally, for patients with progressive ASCVD and high plasma Lp(a), a possible approach sometimes used is lipoprotein apheresis [72].…”

Section: Lp(a)-novelties In the Era Of Rna-based Therapiesmentioning

confidence: 99%

Lipid Lowering Drugs: Present Status and Future Developments

Ruscica

Ferri

Santos

et al. 2021

Curr Atheroscler Rep

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Purpose of review Based on the recent data of the DA VINCI study, it is clear that, besides utilization of statins, there is a need to increase non-statin lipid lowering approaches to reduce the cardiovascular burden in patients at highest risk. Recent findings For hypercholesterolemia, the small synthetic molecule bempedoic acid has the added benefit of selective liver activation, whereas inclisiran, a hepatic inhibitor of the PCSK9 synthesis, has comparable effects with PCSK9 monoclonal antibodies. For hypertriglyceridemia, cardiovascular benefit has been achieved by the use of icosapent ethyl, whereas results with pemafibrate, a selective agonist of PPAR-α, are eagerly awaited. In the era of RNA-based therapies, new options are offered to dramatically reduce levels of lipoprotein(a) (APO(a)LRX) and of triglycerides (ANGPTL3LRX and APOCIII-LRx). Summary Despite the demonstrated benefits of statins, a large number of patients still remain at significant risk because of inadequate LDL-C reduction or elevated blood triglyceride-rich lipoproteins or lipoprotein(a). The area of lipid modulating agents is still ripe with ideas and major novelties are to be awaited in the next few years.

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“…93 The 25 nmol/L (12 mg/dL) reduction in Lp(a) corresponded to a 15% reduction in CVD events. 94 Data from 4 Phase 3 trials with evolucumab comprising 895 patients showed heterogeneity between LDL-C and Lp(a) effects. 95 Concordance was defined as LDL-C reduction >35% and Lp(a) reduction >10%.…”

Section: Pcsk9 Inhibitors and Lp(a)mentioning

confidence: 99%

Elevated Lipoprotein(a): Background, Current Insights and Future Potential Therapies

Handhle¹,

Viljoen²,

Wierzbicki³

2021

VHRM

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Lipoprotein(a) forms a subfraction of the lipid profile and is characterized by the addition of apolipprotein(a) (apo(a)) to apoB100 derived particles. Its levels are mostly genetically determined inversely related to the number of protein domain (kringle) repeats in apo(a). In epidemiological studies, it shows consistent association with cardiovascular disease (CVD) and most recently with extent of aortic stenosis. Issues with standardizing the measurement of Lp(a) are being resolved and consensus statements favor its measurement in patients at high risk of, or with family histories of CVD events. Major lipid-lowering therapies such as statin, fibrates, and ezetimibe have little effect on Lp(a) levels. Therapies such as niacin or cholesterol ester transfer protein (CETP) inhibitors lower Lp(a) as well as reducing other lipid-related risk factors but have failed to clearly reduce CVD events. Proprotein convertase subtilisin kexin-9 (PCSK9) inhibitors reduce cholesterol and Lp(a) as well as reducing CVD events. New antisense therapies specifically targeting apo(a) and hence Lp(a) have greater and more specific effects and will help clarify the extent to which intervention in Lp(a) levels will reduce CVD events.

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Lipoprotein(a) and PCSK9 inhibition: clinical evidence

Cited by 25 publications

References 20 publications

Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?

Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?

Lipid Lowering Drugs: Present Status and Future Developments

Elevated Lipoprotein(a): Background, Current Insights and Future Potential Therapies

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