Reduced incidence of cardiovascular events in hyper-Lp(a) patients on lipoprotein apheresis. The G.I.L.A. (Gruppo Interdisciplinare Aferesi Lipoproteica) pilot study

Bigazzi, Federico; Sbrana, Francesco; Berretti, Daniele; Grazia, Zenti Maria; Fabris, Antonia; Fonda, M.; Vigna, Giovanni Battista; D'Alessandri, Giovanna; Passalacqua, S.; Pino, Beatrice Dal; Pianelli, Mascia; Luciani, R.; Ripoli, Andrea; Rafanelli, Daniela; Manzato, Enzo; Cattin, Luigi; Sampietro, Tiziana

doi:10.1016/j.transci.2018.07.015

Cited by 18 publications

(8 citation statements)

References 26 publications

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“…This recent analysis confirms previous German evaluations and also a study from Italy evaluating cardiovascular events before initiation of apheresis and during regular apheresis therapy [ 49 , 50 •, 51 , 52 ]. In two of the German studies, only subjects with isolated Lp(a) elevation were included (with LDL < 2.5 mmol/l (97 mg/dl) on statin therapy) [ 51 , 52 ], while in the third study, patients with concomitantly elevated LDL-cholesterol were also included [ 50 •].…”

Section: Recent Evidence Of Therapeutic Benefit Of Lipoprotein Apheresupporting

confidence: 88%

Current Role of Lipoprotein Apheresis

Thompson

Parhofer

2019

Curr Atheroscler Rep

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Purpose of Review Lipoprotein apheresis is a very efficient but time-consuming and expensive method of lowering levels of lowdensity lipoprotein cholesterol, lipoprotein(a)) and other apoB containing lipoproteins, including triglyceride-rich lipoproteins. First introduced almost 45 years ago, it has long been a therapy of "last resort" for dyslipidaemias that cannot otherwise be managed. In recent years new, very potent lipid-lowering drugs have been developed and the purpose of this review is to define the role of lipoprotein apheresis in the current setting. Recent Findings Lipoprotein apheresis still plays an important role in managing patients with homozygous FH and some patients with other forms of hypercholesterolaemia and cardiovascular disease. In particular, patients not achieving treatment goals despite modern lipid-lowering drugs, either because these are not tolerated or the response is insufficient. Recently, lipoprotein(a) has emerged as an important cardiovascular risk factor and lipoprotein apheresis has been used to decrease lipoprotein(a) concentrations in patients with marked elevations and cardiovascular disease. However, there is considerable heterogeneity concerning the recommendations by scientific bodies as to which patient groups should be treated with lipoprotein apheresis. Summary Lipoprotein apheresis remains an important tool for the management of patients with severe drug-resistant dyslipidaemias, especially those with homozygous FH.

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Section: Recent Evidence Of Therapeutic Benefit Of Lipoprotein Apheresupporting

confidence: 88%

Current Role of Lipoprotein Apheresis

Thompson

Parhofer

2019

Curr Atheroscler Rep

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“…For some patients with diabetes and increased Lp(a), such therapies may enter the clinic soon [58, 59]. The long-term efficacy of lipoprotein apheresis on morbidity in patients with elevated Lp(a) and chronic ischemic heart disease on maximally tolerated lipid-lowering therapy is well documented [60].…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein (a) interactions with cholesterol-containing lipids on angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion

Shen

Chen

Dai

et al. 2019

Cardiovasc Diabetol

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Background We investigated whether or to what extent the interaction of lipoprotein (a) [Lp(a)] with cholesterol-containing lipids was associated with angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion. Methods Serum levels of Lp(a), total cholesterol, low-density lipoprotein–cholesterol (LDL-C), high-density lipoprotein–cholesterol (HDL-C), and triglyceride were determined and non-HDL-C was calculated in 706 type 2 diabetic and 578 non-diabetic patients with stable coronary artery disease and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3). Results For diabetic and non-diabetic patients, Lp(a), total cholesterol, LDL-C, and non-HDL-C levels were higher in patients with poor coronary collateralization than in those with good collateralization, whereas HDL-C and triglyceride levels were similar. After adjustment for potential confounding factors, tertiles of Lp(a), total cholesterol, LDL-C and non-HDL-C remained independent determinants for poor collateralization. A significant interaction between Lp(a) and total cholesterol, LDL-C or non-HDL-C was observed in diabetic patients (all P interaction < 0.001) but not in non-diabetics. At high tertile of total cholesterol (≥ 5.35 mmol/L), LDL-C (≥ 3.36 mmol/L) and non-HDL-C (≥ 4.38 mmol/L), diabetic patients with high tertile of Lp(a) (≥ 30.23 mg/dL) had an increased risk of poor collateralization compared with those with low tertile of Lp(a) (< 12.66 mg/dL) (adjusted OR = 4.300, 3.970 and 4.386, respectively, all P < 0.001). Conclusions Increased Lp(a) confers greater risk for poor coronary collateralization when total cholesterol, LDL-C or non-HDL-C are elevated especially for patients with type 2 diabetes. Electronic supplementary material The online version of this article (10.1186/s12933-019-0888-z) contains supplementary material, which is available to authorized users.

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“…Currently, LA is mainly used in two different clinical settings, i.e., significantly elevated LDL-C or Lp(a). In patients with hyperlipoproteinemia(a), and on maximally tolerated lipid-lowering medications, LA seems to lower the progression of atherosclerosis, leading to a reduced number of CV events [ 109 , 110 , 111 ]. In the case of CV events, when comparing the time intervals from the start of LA to a similar time on no LA, LA may lead to a more than 80% risk-reduction [ 112 , 113 , 114 ].…”

Section: Lipoprotein Apheresis (La) To Reduce Lipoprotein(a)mentioning

confidence: 99%

Lipoprotein(a) Lowering—From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

Greco

Sirtori

Corsini

et al. 2020

JCM

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It is well-known that elevated lipoprotein(a)—Lp(a)—levels are associated with a higher risk of cardiovascular (CV) mortality and all-cause mortality, although a standard pharmacotherapeutic approach is still undefined for patients with high CV risk dependent on hyperlipoproteinemia(a). Combined with high Lp(a) levels, familial hypercholesterolemia (FH) leads to a greater CVD risk. In suspected FH patients, the proportion of cases explained by a rise of Lp(a) levels ranges between 5% and 20%. In the absence of a specific pharmacological approach able to lower Lp(a) to the extent required to achieve CV benefits, the most effective strategy today is lipoprotein apheresis (LA). Although limited, a clear effect on Lp(a) is exerted by PCSK9 antagonists, with apparently different mechanisms when given with statins (raised catabolism) or as monotherapy (reduced production). In the era of RNA-based therapies, a new dawn is represented by the use of antisense oligonucleotides APO(a)Lrx, able to reduce Lp(a) from 35% to over 80%, with generally modest injection site reactions. The improved knowledge of Lp(a) atherogenicity and possible prevention will be of benefit for patients with residual CV risk remaining after the most effective available lipid-lowering agents.

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Reduced incidence of cardiovascular events in hyper-Lp(a) patients on lipoprotein apheresis. The G.I.L.A. (Gruppo Interdisciplinare Aferesi Lipoproteica) pilot study

Cited by 18 publications

References 26 publications

Current Role of Lipoprotein Apheresis

Current Role of Lipoprotein Apheresis

Lipoprotein (a) interactions with cholesterol-containing lipids on angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion

Lipoprotein(a) Lowering—From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

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