# New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease

Review · Burger AL, Pogran E, Muthspiel M, Kaufmann CC, Jäger B, Huber K

- Archive id: doi:10.3390/biomedicines10050970
- Published: 2022-04-22
- Venue: Biomedicines
- DOI: https://doi.org/10.3390/biomedicines10050970
- PMID: 35625707
- PMCID: PMC9138506
- Citations: 12
- Source URL: https://doi.org/10.3390/biomedicines10050970
- PDF: https://europepmc.org/articles/PMC9138506/pdf
- Provenance: europepmc

## Abstract

The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach the recommended treatment goal of \<55 mg/dL (\<1.4 mmol/L). Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of “the lower, the better”, we also discuss the concept of “the earlier, the better”, which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cardiovascular Therapeutics](https://space-kitty.com/topics/cardiovascular-innovation)

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