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Review
. 2022 Mar;22(2):141-155.
doi: 10.1007/s40256-021-00497-3. Epub 2021 Sep 13.

Lipid-Lowering Drug Therapy: Critical Approach for Implementation in Clinical Practice

Maddalena Rossi  1 , Enrico Fabris  1 , Davide Barbisan  1 , Laura Massa  1 , Gianfranco Sinagra  2
Affiliations
Review

Lipid-Lowering Drug Therapy: Critical Approach for Implementation in Clinical Practice

Maddalena Rossi et al. Am J Cardiovasc Drugs. 2022 Mar.

Abstract

Increased levels of low-density lipoprotein cholesterol (LDL-C) are recognized as a primary risk factor for atherosclerotic cardiovascular disease, which remains the leading cause of death worldwide. Lowering LDL-C levels clearly reduces the risk of cardiovascular events, with benefits related to both absolute reduction and duration of treatment; however, a threshold below which low LDL-C levels can be dangerous has never been established. Since the discovery of statins, cardiovascular research has focused on developing new lipid-lowering agents. Ezetimibe and proprotein convertase subtilisin-kexin type 9 inhibitors have been found to further reduce LDL-C values and subsequent cardiovascular risk. Novel recently approved inclisiran and bempedoic acid, currently being tested in cardiovascular outcomes studies, are further expanding our pharmacological armamentarium, enabling the clinician to diminish residual risk related to LDL-C. Moreover, new agents are paving the way to successful treatment of homozygous familial hypercholesterolemia. This review summarizes the main characteristics of current and emerging lipid-lowering therapies to assist with comprehensive evidence-based decision making.

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Conflict of interest statement

Maddalena Rossi, Enrico Fabris, Davide Barbisan, Laura Massa, and Gianfranco Sinagra have no conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Mechanisms of action of statins, ezetimibe, PCSK9i mAbs, bempedoic acid, and inclisiran. ATP-CL ATP citrate lyase, CoA coenzyme A, LDL-C low-density lipoprotein cholesterol, LDL-R low-density lipoprotein receptor, mAbs monoclonal antibodies, mRNA messenger RNA, PCSK9 proprotein convertase subtilisin-kexin type 9
Fig. 2
Fig. 2
The arrows connect every drug with specific characteristics of patients, on the basis of inclusion/exclusion criteria of corresponding RCTs. Orange arrows suggest exclusive links. ACS acute coronary syndrome, CT computed tomography, CV cardiovascular , eGFR estimated glomerular filtration rate, MI myocardial infarction, NYHA New York Heart Association, OATP organic anion-transporting peptide, PAD peripheral artery disease, TG triglyceride
Fig. 3
Fig. 3
Optimization of lipid-lowering therapy during hospitalization for acute coronary syndrome. ApoB apolipoprotein B, EAS European Atherosclerosis Society, ESC European Society of Cardiology, LDL-C low-density lipoprotein cholesterol, LLT lipid-lowering therapy, mAbs monoclonal antibodies, PCSK9i proprotein convertase subtilisin-kexin type 9 inhibitor
See this image and copyright information in PMC

References

    1. Mathers CD, Loncar D. Projections of Global Mortality and Burden of Disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. doi: 10.1371/journal.pmed.0030442. - DOI - PMC - PubMed
    1. Centre for Economics and Business Research. The economic cost of cardiovascular disease from 2014-2020 in six European economies. 2020.
    1. Lowering blood cholesterol to prevent heart disease. NIH Consensus Development Conference statement. Arteriosclerosis 5(4):404–12. http://www.ncbi.nlm.nih.gov/pubmed/3839391. - PubMed
    1. Yusuf S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet (Lond, Engl) 2004;364(9438):37–52. doi: 10.1016/S0140-6736(04)17018-9. - DOI - PubMed
    1. Sinning D, Landmesser U. Low-density lipoprotein-cholesterol lowering strategies for prevention of atherosclerotic cardiovascular disease: focus on siRNA treatment targeting PCSK9 (Inclisiran) Curr Cardiol Rep. 2020;22(12):176. doi: 10.1007/s11886-020-01427-6. - DOI - PMC - PubMed

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