Journal of Translational Research

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Opinion Article - Journal of Translational Research (2023) Volume 7, Issue 1

Lipid-lowering therapy on fasting and the effects of evolocumab on lipids and lipoproteins.

Robert Rosenson*

Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, Netherlands

*Corresponding Author:
Robert Rosenson
Department of Vascular Medicine
University Medical Center Utrecht
Utrecht, Netherlands

Received: 02-Jan-2023, Manuscript No. AATR-23-86946; Editor assigned: 06-Jan-2023, Pre QC No. AATR-23-86946(PQ); Reviewed: 17-Jan-2023, QC No. AATR-23-86946; Revised: 23-Jan-2023, Manuscript No. AATR-23-86946(R); Published: 31-Jan-2023, DOI:10.35841/aatr-7.1.135

Citation: Rosenson R. Lipid-lowering therapy on fasting and the effects of evolocumab on lipids and lipoproteins. Am J Transl Res. 2023;7(1):135

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Familial dysbetalipoproteinemia, Proprotein convertase subtilin kexin 9Evolocumab, Clinical trial Non-HDLcholesterol.


Adeno-associated virus vectors, non-coding RNA therapy, antisense oligonucleotides, and CRISPR/Cas9 based therapeutics. Bempedoic acid is the treatment that most closely resembles statins in its ability to lower cholesterol levels. It is not connected to myopathy, though. Overall, non-statin therapies are expected to become more crucial in managing dyslipidemia, even though statins remain the gold standard. With an estimated prevalence of 1 in 850 to 1 in 3500 people, familial dysbetalipoproteinemia (FD), also known as remnant removal disease is the second most common monogenic lipid disorder after heterozygous familial hypercholesterolemia (heFH) [1].

Because it is not recognised in clinical practise, FD is frequently misdiagnosed. The accumulation of remnants of triglyceride-rich, cholesterol-enriched lipoproteins is a defining feature of FD (TRLs). TRL accumulation in FD is especially pronounced during the postprandial phase, which is associated with a very high risk of CVD and therefore FD patients have a very high risk of premature CVD. TRLs are the cause of atherosclerosis. Increased non-high-density lipoprotein cholesterol (non-HDL-C) levels, which include cholesterol in all atherogenic lipoproteins like chylomicrons, very-low-density lipoproteins (VLDL), their remnants, and low-density lipoprotein, are a reflection.

LDL and LDL-cholesterol (LDL-C) levels in FD patients are typically low or even nonexistent, and as a result, they do not accurately reflect the risk of CVD. LDL-C levels should not be measured in FD because they cannot be measured accurately. Therefore, non-HDL-C levels are used to determine treatment objectives for FD patients. To meet non-HDL-C treatment objectives, medical intervention involving diet, statins, and opportunistically fibrates is advised. Even with optimal therapy, 60% of FD patients in clinical practise fail to meet non-HDL-C treatment goals, demonstrating the need for more intensive lipid-lowering therapy [2,3].

Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies stop the degradation of the LDL-receptor by neutralizing circulating PCSK9 (LDL-R). PCSK9 mAbs have been shown to reduce CVD risk in high-risk patients by 20% and LDL-C by 50–60%. PCSK9 mAbs effectively reduce postprandial TRLs by about 30-40% in people with type 2 diabetes mellitus (T2DM). The goal of the current study was to determine whether patients with FD, who typically have low LDL-C levels and TRLs with dysfunctional apoE that does not bind to the LDL-R, would experience a similar response to PCSK9 mAbs [4].

Our study's large sample size, which included participants from statin monotherapy, statin combination therapy, statinintolerant and heterozygous familial hypercholesterolemia evolocumab trials as well as participants from placebo- and ezetimibe-controlled studies, contributed to the strength of our analysis. Also noted are some of the current study's limitations. We pooled data from various randomised studies as a posthoc analysis, which is one limitation. In order to determine the effectiveness of evolocumab on the distribution of VLDL and LDL particles, we also did not analyse specimens for lipoprotein particle size and concentration. None of the phase 2 or 3 studies included participants with baseline fasting triglycerides 4.52 mmol/L, despite the fact that we saw equivalent efficacy of evolocumab in patients with these levels [5].


PCSK9, apoB, and MTTP inhibitors can significantly lower plasma levels of LDL-C and apoB when used alone or in conjunction with statins. These effects are especially important for high-risk people who have severe hypercholesterolemia, such as those who have a family history of the condition. PCSK9 inhibitors are likely to be more frequently prescribed in patients at high risk for CVD, especially those who are resistant to or intolerant of high-intensity statin therapy. Although the use of mipomersen and lomitapide is restricted to severe familial hypercholesterolemia as a replacement for LDL-apheresis. Although PCSK9 mAbs are effective and have a good safety profile, their long-term effect on cardiovascular events is still being researched. However, it is debatable whether PCSK9 mAbs reduce the rates of recurrent cardiovascular events.


  1. Robinson JG, Nedergaard BS, Rogers WJ, et al. Effect of evolocumab or ezetimibe added to moderate-or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: The LAPLACE-2 randomized clinical trial. Jama. 2014;311(18):1870-83.
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  9. Koopal C, Marais AD, Westerink J, et al. Effect of adding bezafibrate to standard lipid-lowering therapy on post-fat load lipid levels in patients with familial dysbetalipoproteinemia. A randomized placebo-controlled crossover trial. JLR. 2017;58(11):2180-7.
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