Novel Therapies for Dyslipidaemias and Atherosclerosis

This literature review investigates new treatment targets and therapeutics for dyslipidaemias and atherosclerosis and their role in decreasing the risk of cardiovascular events in adults. Apart from emerging research on new drug therapies to decrease the cardiovascular risk through LDL-C, more and more data directs attention to other markers and potential treatment targets of dyslipidaemia. Namely the focus is on high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein (α) (Lp(a)), apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) and their relevance in cardiovascular risk (CV) management by analysing the current scientific literature using the PubMed database, including human trials published between 2019 and 2023. The review identifies a large residual CV risk despite effective LDL-C lowering treatment approaches with statins, PCSK9 inhibitors and ezetimibe. It has been widely detected that low HDL-C level are associated with an increased CV risk but in recent studies high HDL-C levels have not only shown no protective effect on CV events but have even been associated with an increase in CV risk. HDL-C levels between 40 mg/dL (50 mg /dL in women) and 80 mg/dL appear not associated with an increased CV risk. Using these cut-offs an HDL-C measurement may be useful in a more individualized CV risk stratification. To better understand HDL-functionality more research is warranted investigating HDL-C and CEC in different settings and stages of inflammation. Apart from LDL-C and HDL-C, TGs are one of three main lipid markers in regard to CV risk modification. More than one third of patients on statins are struggling with elevated TGs. IPE, an established treatment for hypertriglyceridemia still requires further supportive data. It is also necessary to determine a common target value, possibly approaching 100 or 150 mg/dL. With the development of new drugs targeting TGs, the focus should be on determining the optimal TG level for CV event reduction. Especially ASOs, like vupanorsen and volanesorsen have shown significant reductions in TGs in phase II and III trials, respectively. The antibody evinacumab has also produced TG reductions up to 80%, even though most studies have consisted of very small cohort and apart from one exception included phase I and II studies only so far. The newer lipid markers gaining popularity and as for TG, Lp(a), apoB and non-HDL-C have as well demonstrated their significance in CV risk reduction. Lp(a) still requires a lot more research before being more thoroughly incorporated into daily clinical practice, but recent antibody trials with alirocumab and evolocumab are promising. ApoB and non-HDL-C may be measured and focused on already, their significance and practicality has been widely proven, and more precise real-life data is warranted to determine optimal goals and the effect of other drugs and individual factors. Future studies may consider a cut-off of apoB levels at around 90mg/dL as suggested by results so far. New drug classes such as siRNAs, antisense oligonucleotides and monoclonal antibodies show consistent results in reducing not only LDL-C in many cases, but also affecting TGs, Lp(a), non-HDL-C and/or ApoB. More research is warranted to identify the impact on each lipid marker individually to exclude possible interactions. The trend in treating dyslipidaemias and atherosclerosis is moving towards a more individualized approach, taking some distance from only focusing on lowering LDL-C as much as possible, but also taking other markers into account, which may be modified by the new drugs.

Šioje literatūros apžvalgoje nagrinėjami nauji dislipidemijų ir aterosklerozės gydymo tikslai ir gydymo būdai bei jų vaidmuo mažinant suaugusiųjų širdies ir kraujagyslių reiškinių riziką. Be naujų tyrimų, susijusių su naujais vaistais, mažinančiais širdies ir kraujagyslių ligų riziką per MTL-C, vis daugiau duomenų nukreipia dėmesį į kitus žymenis ir galimus dislipidemijos gydymo tikslus. Pagrindinis dėmesys skiriamas didelio tankio lipoproteinams cholesteroliui (DTL-C), trigliceridams (TG), lipoproteinams (α) (Lp(a)), apolipoproteinui B (apoB) ir nedidelio tankio lipoproteinų cholesteroliui (ne DTL). C) ir jų svarbą valdant kardiovaskulinę riziką (CV), analizuojant dabartinę mokslinę literatūrą naudojant PubMed duomenų bazę, įskaitant tyrimus su žmonėmis, paskelbtus 2019–2023 m. Apžvalgoje nustatyta didelė liekamoji CV rizika, nepaisant veiksmingo MTL cholesterolio kiekį mažinančio gydymo statinais, PCSK9 inhibitoriais ir ezetimibu. Tyrimai parodė, kad DTL-C padidino CV riziką labai mažu, bet ir dideliu lygiu. Kuriant naujus vaistus, skirtus TG, pagrindinis dėmesys turėtų būti skiriamas optimalaus TG lygio nustatymui CV įvykių mažinimui. Ypač ASO, pavyzdžiui, vupanorsen ir volanesorsen, žymiai sumažino TG. Populiarėjantys naujesni lipidų žymenys, kaip ir TG, Lp(a), apoB ir ne HDL-C, taip pat įrodė savo reikšmę mažinant CV riziką. Naujos vaistų klasės, tokios kaip siRNR, antisensiniai oligonukleotidai ir monokloniniai antikūnai, rodo nuoseklius rezultatus daugeliu atvejų sumažindamos ne tik MTL-C, bet ir paveikdamos TG, Lp(a), ne DTL-C ir (arba) ApoB. Reikia atlikti daugiau tyrimų, siekiant nustatyti poveikį kiekvienam lipidų žymeniui atskirai, kad būtų išvengta galimos sąveikos. Dislipidemijų ir aterosklerozės gydymo tendencija juda prie labiau individualizuoto požiūrio.