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Review
. 2024 Sep 20;16(9):e69824.
doi: 10.7759/cureus.69824. eCollection 2024 Sep.

Efficacy of Traditional Anti-lipidemic Drugs in Lowering Lipoprotein(a) Levels: A Systematic Review

Mohit Sinha  1 , Rafik Maged  2 , Pakeeza Tarar  3 , Venkata Varshitha Bandi  4 , Hema Manvi Koneru  5 , Hooria Sarwar  6
Affiliations
Review

Efficacy of Traditional Anti-lipidemic Drugs in Lowering Lipoprotein(a) Levels: A Systematic Review

Mohit Sinha et al. Cureus. .

Abstract

Lipoprotein(a), or Lp(a), was identified in the early 1960. Its role as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) became widely recognized by the late 20th century, regardless of other traditional risk markers such as low-density lipoproteins and high-density lipoproteins. This study aimed to systematically review available literature and compare the efficacy of different lipid-lowering drugs, both approved for clinical use and currently undergoing trials, in lowering Lp(a) levels. A comprehensive search of medical databases including PubMed, PubMed Central (PMC), Medline, ScienceDirect, Cochrane Library, and Google Scholar was conducted to identify relevant studies. A total of 29 research papers met the inclusion criteria, focusing on the impact of various lipid-lowering drugs on Lp(a) concentration in patients with significantly elevated baseline Lp(a) levels. Plasma Lp(a) levels exceeding 30 mg/dL are associated with a higher risk of ASCVD, including myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and increased all-cause mortality. Most commonly used lipid-lowering agents, such as statins, fibrates, ezetimibe, and nutraceuticals like coenzyme Q10 (CoQ10), showed no significant effect on Lp(a) plasma levels. However, Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were found to effectively reduce plasma Lp(a) concentrations. Emerging therapies targeting apolipoprotein(a) RNA, including anti-sense oligonucleotides (ASO) and small interfering RNA (siRNA), significantly reduced Lp(a) levels in Phase 2 trials. While several lipid-lowering agents have minimal impact on Lp(a) levels, therapies like Lp(a) apheresis, PCSK-9 inhibitors, and novel RNA-targeting drugs show promise in effectively reducing Lp(a) concentrations. However, whether these reductions translate into decreased cardiovascular events remains to be determined.

Keywords: antisense oligonucleotides; apheresis therapy; ascvd; lipoprotein (a); lp(a); pcsk-9 inhibitor; small interfering rna; statins.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. CVD as the primary cause of mortality from 1990 to 2019.
Adapted from [1] CVD: Cardiovascular Disease
Figure 2
Figure 2. PRISMA flowchart describing the data collection and study selection processes.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
See this image and copyright information in PMC

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