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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
When to lower triglycerides?
1Clinical Research and Adult Diabetes sections, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Insights
High triglyceride-rich particles (TRL) increase cardiovascular risk. Icosapent-ethyl (IPE), an omega-3 fatty acid, significantly reduced ASCVD events in high-risk patients, suggesting novel therapeutic benefits beyond triglyceride lowering.
Area of Science:
- Cardiology
- Metabolic Syndrome
- Pharmacology
Background:
- Residual risk of atherosclerotic cardiovascular disease (ASCVD) events persists despite statin therapy.
- Triglyceride-rich particles (TRL) and associated dyslipidemia factors contribute to atherogenesis.
- Increasing prevalence of high triglycerides linked to lifestyle, obesity, and diabetes.
Purpose of the Study:
- To review the role of TRL in ASCVD.
- To evaluate therapeutic strategies for residual dyslipidemia.
- To assess the impact of icosapent-ethyl (IPE) on ASCVD events.
Main Methods:
- Review of clinical trial data on fibrates, niacin, and omega-3 fatty acids (OM3FA).
- Analysis of evidence linking TRL to atherogenesis.
- Evaluation of IPE's effect on ASCVD events in high-risk populations.
Main Results:
- Past trials with fibrates and niacin showed no ASCVD benefit post-statin.
- Icosapent-ethyl (IPE) demonstrated a 25% ASCVD event reduction in high-risk patients.
- IPE's benefits may stem from unique biological effects beyond triglyceride reduction.
Conclusions:
- IPE shows promise in preventing ASCVD events in high-risk individuals.
- Novel agents like Apo C-III inhibitors may benefit patients with very high triglycerides.
- Further research into TRL management and novel therapies is warranted.
Purpose Of Review:
Substantial risk of ASCVD events persists despite intensive statin therapy and other agents to lower LDL-C. The optimal way to address other elements of dyslipidemia, such as triglyceride-rich particles (TRL) and when to treat has remained unclear.
Recent Findings:
Several lines of evidence indicate that TRL are associated with atherogenesis, partly because of associated factors, such as cholesterol-enriched remnant particles, high LDL particle number, high apo-B, high apo-CIII, and others. High triglyceride is increasingly prevalent because of worsening of lifestyle factors, obesity, and diabetes. Trials with fibrates, and niacin to reduce residual dyslipidemia have not provided evidence of benefits after statin therapy, thus far. A recent trial with an omega 3 fatty acid (OM3FA), icosapent-ethyl (IPE), provided evidence for a 25% reduction in ASCVD events in statin-treated high-risk population. These results were unexplained by triglyceride reduction alone, and are likely related to unique biologic effects of IPE on atherosclerosis. Finally, in patients with very high triglycerides, lifestyle measures and several triglyceride-lowering agents are indicated, often in combination, to prevent episodes of pancreatitis. A novel Apo C-III inhibitor may provide additional benefit in such patients.
Summary:
There is evidence for the benefits of IPE in preventing ASCVD events. A novel fibrate is in clinical trials.
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