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Tackling Residual Atherosclerotic Risk in Statin-Treated Adults: Focus on Emerging Drugs
Kohei Takata1, Stephen J Nicholls2,3
1South Australian Health and Medical Research Institute, SAHMRI North Terrace, Adelaide, SA, 5001, Australia.
Insights
Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for reducing cardiovascular events. This review explores targeting atherogenic lipoproteins to address residual cardiovascular risk in patients treated with statins.
Area of Science:
- Cardiology
- Genomics
- Metabolic Research
Background:
- Epidemiological studies confirm the benefit of lowering low-density lipoprotein cholesterol (LDL-C) for cardiovascular event reduction.
- Residual cardiovascular risk persists in patients with optimal LDL-C on statins, necessitating further therapeutic strategies.
- Statin intolerance also underscores the need for alternative approaches to manage cardiovascular risk.
Purpose of the Study:
- To review the evidence supporting the targeting of atherogenic lipoproteins for residual atherosclerotic cardiovascular disease (ASCVD) risk reduction.
- To highlight novel therapeutic targets in lipid metabolism informed by genomic insights.
- To discuss the role of triglyceride (TG)-rich lipoproteins in ASCVD and emerging TG-targeting therapies.
Main Methods:
- Review of epidemiological studies and meta-analyses on LDL-C reduction and cardiovascular events.
- Analysis of mechanistic studies, including intracoronary imaging, on disease progression despite statin therapy.
- Examination of genomic insights into novel lipid metabolism targets and clinical trial data for emerging therapies.
Main Results:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown a beneficial impact on cardiovascular outcomes.
- Triglyceride (TG)-rich lipoproteins are increasingly recognized as a causal factor in atherosclerotic cardiovascular disease (ASCVD).
- Several promising therapies targeting TG-rich lipoproteins are in various stages of clinical development.
Conclusions:
- Targeting atherogenic lipoproteins represents a promising strategy to reduce residual ASCVD risk in statin-treated patients.
- Novel therapeutic targets in lipid metabolism are emerging from genomic research.
- Further investigation and clinical application of TG-targeting therapies are warranted to improve cardiovascular outcomes.
Abstract:
Epidemiological studies and meta-analyses have consistently suggested the importance of lowering low-density lipoprotein cholesterol (LDL-C) to reduce cardiovascular (CV) events. However, these studies and mechanistic studies using intracoronary imaging modalities have reported patients who continue to experience CV events or disease progression despite optimal LDL-C levels on statins. These findings, including statin intolerance, have highlighted the importance of exploring additional potential therapeutic targets to reduce CV risk. Genomic insights have presented a number of additional novel targets in lipid metabolism. In particular, proprotein convertase subtilisin/kexin type 9 inhibitors have rapidly developed and recently demonstrated their beneficial impact on CV outcomes. Triglyceride (TG)-rich lipoproteins have been recently reported as a causal factor of atherosclerotic cardiovascular disease (ASCVD). Indeed, several promising TG-targeting therapies are being tested at various clinical stages. In this review, we present the evidence to support targeting atherogenic lipoproteins to target residual ASCVD risk in statin-treated patients.
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