Abstract
Lipid-driven cardiovascular disease (CVD) risk is caused by atherogenic apolipoprotein B (apoB) particles containing low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein(a) [Lp(a)] and resembles a large and modifiable proportion of the total CVD risk. While a surplus of novel lipid-lowering therapies has been developed in recent years, management of lipid-driven CVD risk in the Netherlands remains suboptimal. To lower LDL‑C levels, statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibiting antibodies are the current standard of therapy. With the approval of bempedoic acid and the silencing RNA inclisiran, therapeutic options are expanding continuously. Although the use of triglyceride-lowering therapies remains a matter of debate, post hoc analyses consistently show a benefit in subsets of patients with high triglyceride or low high-density lipoprotein cholesterol levels. Pemafibrate and novel apoC-III could be efficacious options when approved for clinical use. Lp(a)-lowering therapies such as pelacarsen are under clinical investigation, offering a potent Lp(a)-lowering effect. If proven effective in reducing cardiovascular endpoints, Lp(a) lowering holds promise to be the third axis of effective lipid-lowering therapies. Using these three components of lipid-lowering treatment, the contribution of apoB-containing lipid particles to the CVD risk may be fully eradicated in the next decade.
Highlights
An atherogenic lipid profile is one of the most important risk factors for atherosclerotic cardiovascular disease (CVD) [1]
The largest proportion of the lipid-driven CVD risk is caused by low-density lipoprotein cholesterol (LDL-C) containing apolipoprotein B lipoproteins
Inhibition of angiopoietinlike protein 3 (ANGPTL3) with evinacumab was recently shown to be effective in reducing LDL-C levels by 49% in a phase 3 trial with 65 familial hypercholesterolaemia (FH) patients already maximally treated with lipid-lowering therapies [37]
Summary
An atherogenic lipid profile is one of the most important risk factors for atherosclerotic cardiovascular disease (CVD) [1]. Available PCSK9 inhibitors are monoclonal antibodies which are administered subcutaneously twice monthly: evolocumab and alirocumab They were proven effective in the FOURIER and ODYSSEY OUTCOMES trials, respectively, comprising a total of 46,488 patients, showing an additional reduction of 59–62% in LDL-C when given in addition to statin therapy [21, 22]. Both studies led to an additional 15% MACE reduction after a mean follow-up of 2.2 and 2.8 years respectively. Treatment with PCSK9 inhibitors can result in flu-like symptoms in a small proportion of patients
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