Lipid Management to Reduce Risk of Cardiovascular Events

Mark Drazner^*
*Correspondence: Mark Drazner, Department of Cardiology, University of Texas, Dallas, Texas, USA, Email:

Introduction

Hypertriglyceridemia, a condition characterized by elevated levels of triglycerides in the bloodstream, is a significant risk factor for cardiovascular disease. Patients with high or very high cardiovascular risk often require aggressive lipid management to reduce their risk of cardiovascular events. Icosapent ethyl, a highly purified form of eicosapentaenoic acid has emerged as a promising therapeutic option for the treatment of hypertriglyceridemia. In this article, we will explore the role of icosapent ethyl in managing hypertriglyceridemia in patients with high or very high cardiovascular risk, including its mechanisms of action, clinical efficacy, safety profile, and implications for cardiovascular prevention. Elevated levels of triglycerides in the bloodstream have been consistently associated with an increased risk of cardiovascular events, including coronary artery disease stroke and peripheral artery disease. Hypertriglyceridemia is often a component of the atherogenic dyslipidemia commonly observed in individuals with metabolic syndrome, type 2 diabetes, and obesity. High triglyceride levels can lead to the accumulation of triglyceride-rich lipoproteins in arterial walls, contributing to atherosclerosis, plaque formation, and vessel narrowing. Elevated triglycerides are associated with increased inflammation, which is a key driver of atherosclerosis and plaque instability. Triglyceride-rich lipoproteins can impair endothelial function, disrupting the protective lining of blood vessels and promoting atherosclerosis. Hypertriglyceridemia is linked to an increased risk of thrombotic events, such as myocardial infarction and stroke, due to its prothrombotic effects. Icosapent ethyl is a highly purified ethyl ester of eicosapentaenoic acid one of the omega-3 fatty acids found in fish oil. Its precise mechanisms of action in managing hypertriglyceridemia and reducing cardiovascular risk. Icosapent ethyl lowers serum triglyceride levels by reducing the production of very-lowdensity lipoprotein particles in the liver and enhancing their clearance from circulation [1].

Description

EPA, the active component of icosapent ethyl, has anti-inflammatory properties that can mitigate the inflammatory processes associated with atherosclerosis. EPA can improve endothelial function by increasing the production of nitric oxide, a molecule that relaxes blood vessels and supports healthy vascular function. Icosapent ethyl may stabilize atherosclerotic plaques, reducing the risk of plaque rupture and thrombosis. The landmark REDUCE-IT trial demonstrated the clinical efficacy of icosapent ethyl in reducing cardiovascular events in high-risk patients with hypertriglyceridemia. The primary endpoint of the REDUCE-IT trial was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and hospitalization for unstable angina. Icosapent ethyl significantly reduced the risk of this composite endpoint by 25% compared to placebo. Icosapent ethyl reduced the risk of several individual components of the primary endpoint, including cardiovascular death, myocardial infarction and stroke. Subgroup analyses indicated that the greatest benefit was observed in patients with higher baseline triglyceride levels and in those with established cardiovascular disease or diabetes. Icosapent ethyl was well-tolerated, with a safety profile similar to that of placebo. There were no significant differences in adverse events, including bleeding events, between the two groups. The clinical benefits of icosapent ethyl are most pronounced in patients with high or very high cardiovascular risk and elevated triglyceride levels. Patient selection and eligibility criteria for treatment with icosapent ethyl typically. Patients with a history of cardiovascular events that place them at high or very high cardiovascular risk. Individuals with fasting triglyceride levels above a certain threshold may vary depending on guidelines and local practice [2].

Patients receiving statin therapy to manage their low-density lipoprotein cholesterol levels who still have elevated triglycerides may be considered for the addition of icosapent ethyl. Clinicians often use their clinical judgment to assess the overall cardiovascular risk of individual patients and determine whether the potential benefits of icosapent ethyl outweigh the risks. Icosapent ethyl has demonstrated a favorable safety profile in clinical trials, including the REDUCE-IT trial. Common adverse events associated with icosapent ethyl include gastrointestinal symptoms such as diarrhea and abdominal discomfort, although these are typically mild and transient. Notably, icosapent ethyl did not increase the risk of bleeding events in the REDUCE-IT trial, making it a valuable option for patients at risk of bleeding complications. Additionally, there were no significant differences in adverse events, including major adverse cardiac events, between the icosapent ethyl and placebo groups. Healthcare providers should assess patients' cardiovascular risk and lipid profiles, including triglyceride levels, to identify those who may benefit from icosapent ethyl therapy. In patients with high or very high cardiovascular risk and persistent hypertriglyceridemia despite statin therapy, consideration should be given to the addition of icosapent ethyl. Icosapent ethyl therapy should be complemented by lifestyle modifications, including a heart-healthy diet, regular exercise, and smoking cessation, to optimize cardiovascular risk reduction. Regular monitoring of lipid profiles and adherence to treatment are essential to ensure therapeutic goals are met. Healthcare providers should engage in shared decision-making with their patients, discussing the potential benefits and risks of icosapent ethyl therapy. Icosapent ethyl represents a valuable therapeutic option for managing hypertriglyceridemia in patients with high or very high cardiovascular risk [3].

Its ability to lower triglycerides, reduce cardiovascular events, and exhibit a favorable safety profile makes it an important addition to the armamentarium of cardiovascular disease prevention strategies. As with any medication, individualized patient assessment, shared decision-making, and a comprehensive approach to cardiovascular risk management are essential for optimizing outcomes in this patient population. Further research and clinical experience will continue to refine our understanding of the role of icosapent ethyl in cardiovascular prevention. Hypertriglyceridemia, a condition characterized by elevated levels of triglycerides in the blood, is an independent risk factor for cardiovascular disease. Patients with high or very high cardiovascular risk, often due to a combination of factors such as obesity, diabetes, and metabolic syndrome, face an increased likelihood of experiencing adverse cardiovascular events. Managing hypertriglyceridemia in these individuals is crucial to reduce the risk of CVD. Icosapent ethyl, a highly purified omega-3 fatty acid, has emerged as a therapeutic option for treating hypertriglyceridemia and lowering cardiovascular risk. In this article, we will explore the role of icosapent ethyl in the treatment of hypertriglyceridemia in patients with high/very high cardiovascular risk, examining its mechanism of action, clinical evidence, and implications for patient care. Hypertriglyceridemia is defined as fasting triglyceride levels of 150 milligrams per deciliter or higher and is a common lipid abnormality in individuals with or at risk for CVD. Elevated triglyceride levels are associated with various metabolic disturbances, including insulin resistance, obesity, and a pro-inflammatory state, all of which contribute to increased cardiovascular risk. Elevated TG levels contribute to the formation of atherogenic lipoprotein remnants, such as very-low-density lipoprotein remnants. These remnants are highly atherogenic and promote the development of atherosclerosis. Hypertriglyceridemia is often accompanied by increased production of very-low-density lipoprotein by the liver [4].

Excess VLDL particles can lead to the accumulation of cholesterol in arterial walls. High triglyceride levels are often associated with reduced HDL cholesterol levels and impaired HDL functionality, which is vital for reverse cholesterol transport and cardiovascular protection. Elevated TG levels can contribute to systemic inflammation, endothelial dysfunction, and oxidative stress, all of which are involved in the pathogenesis of atherosclerosis and CVD. Icosapent ethyl is a highly purified form of eicosapentaenoic acid one of the omega-3 fatty acids found in fish oil. Icosapent ethyl primarily targets hypertriglyceridemia by reducing the production of VLDL particles and enhancing the clearance of TG-rich lipoproteins from the bloodstream. In addition to its lipid-lowering properties, EPA has anti-inflammatory effects. It can reduce markers of inflammation, such as C-reactive protein and mitigate the pro-inflammatory processes associated with hypertriglyceridemia. Icosapent ethyl has demonstrated cardiovascular benefits beyond triglyceride reduction. Clinical trials have shown reductions in major adverse cardiovascular events including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and unstable angina, in patients with elevated cardiovascular risk. Patients were randomized to receive either icosapent ethyl or placebo, in addition to statin therapy. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina. Icosapent ethyl significantly reduced the risk of the primary composite endpoint by compared to placebo, demonstrating a substantial reduction in major cardiovascular events. Patients in the icosapent ethyl group experienced a significant reduction in triglyceride levels, along with other favorable lipid changes, including a decrease in VLDL cholesterol. Icosapent ethyl led to a reduction in inflammatory markers, such as CRP, suggesting an anti-inflammatory benefit beyond lipid modification. HDL cholesterol levels remained stable, mitigating concerns about potential reductions in beneficial cholesterol. The findings from the REDUCE-IT trial have significant implications for the management of hypertriglyceridemia and cardiovascular risk in patients with high/very high cardiovascular risk [5].

Conclusion

Cardiovascular risk management in these patients should involve a multifactorial approach that includes lipid modification, blood pressure control, glucose management, and lifestyle interventions. The decision to initiate icosapent ethyl should be individualized, taking into account each patient's specific cardiovascular risk profile, including triglyceride levels, comorbidities, and treatment goals. Regular monitoring of lipid levels, including triglycerides, is essential to assess treatment efficacy and adherence. Adjustments to therapy may be necessary based on the patient's response. Statin therapy remains a cornerstone of cardiovascular risk reduction. Patients should be encouraged to adhere to statin therapy as prescribed. Shared decision-making between healthcare providers and patients is critical to ensure that treatment decisions align with patients' preferences and goals. Icosapent ethyl has demonstrated a favorable safety profile in clinical trials, with the most common adverse event being a modest increase in LDL cholesterol levels. Gastrointestinal symptoms, such as diarrhea, were reported in some patients but were generally mild and transient. It is important for healthcare providers to discuss potential side effects and benefits with patients when considering icosapent ethyl therapy. Icosapent ethyl is a valuable therapeutic option for patients with high/very high cardiovascular risk who have elevated triglycerides despite statin therapy. It may be particularly beneficial for those with residual cardiovascular risk.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Karemaker, John M. "An introduction into autonomic nervous function."Physiol Meas38 (2017): R89.

   Google Scholar, Crossref, Indexed at

2. Kita, Toru, Noriaki Kume, Manabu Minami and Kazutaka Hayashida, et al. "Role of oxidized LDL in atherosclerosis."Ann N Y Acad Sci947 (2001): 199-206.

   Google Scholar, Crossref, Indexed at

3. La Meir, Mark, Sandro Gelsomino, Fabiana Lucà and Laurant Pison, et al. "Minimally invasive surgical treatment of lone atrial fibrillation: Early results of hybrid vs. standard minimally invasive approach employing radiofrequency sources."Int J Cardiol 167 (2013): 1469-1475.

   Google Scholar, Crossref, Indexed at

4. Gelsomino, Sandro, Domenico Corradi, Roberto Lorusso and Orlando Parise, et al. "Anatomical basis of minimally invasive epicardial ablation of atrial fibrillation."Eur J Cardiothorac Surg43 (2013): 673-682.

   Google Scholar, Crossref, Indexed at

5. Zotov, Aleksandr, Sergei Vachev, Daniil Borisov and Aleksandr Troitskiy, et al. "Thoracoscopic pulmonary vein and left atrial posterior wall isolation combined with left atrial appendage resection in patients with long-standing persistent atrial fibrillation."Braz J Cardiovasc Surg 35 (2020): 22-27.

   Google Scholar, Crossref, Indexed at