Modern Lipid Management: A Literature Review

Malik, Jahanzeb; Shabeer, Hassan; Ishaq, Uzma; Chauhan, Humaira; Akhtar, Hina Fatima

doi:10.7759/cureus.9375

Cited by 3 publications

(4 citation statements)

References 30 publications

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“…Attention is currently directed at new available lipid-lowering therapies, including Lomitapide, Mipomersen, and PCSK9i (10,12). Both PCSK9i, Evalocomab and Alirocumab, have proven to reduce LDL-C additionally by up to 60% when added to a standard lipid-lowering therapy in heterozygous FH patients with relatively minor side effects (12)(13)(14). In HoFH (both true homozygous and compound heterozygous) and double heterozygous FH patients, the reduction at week 12 is reported to be 30.9% for Evalocomab and 41.2% for Alirocumab (15).…”

Section: Discussionmentioning

confidence: 99%

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Case Report: Difficulties in the Treatment of a 12-Year-Old Patient With Homozygous Familial Hypercholesterolemia, Compound Heterozygous Form − 5 Years Follow-Up

Vladimirova-Kitova

Kitov²,

Ganev

et al. 2021

Front. Cardiovasc. Med.

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The literature review we conducted reveals the limited use of proprotein convertase subtilisin/kexin type 9-inhibitors (PCSK9i) in children with familial hypercholesterolemia (FH). In 2015, a 10-year-old boy presented with round, xanthochromic lesions on his right knee and elbow. The values of total and LDL-cholesterol (LDL-C)−18 and 15 mmol/l, respectively—along with normal triglycerides and HDL-cholesterol (HDL-C) confirmed the lesions were xanthomas. The data suggested a homozygous form of FH. The level of lipoprotein (a) was high: 270 mg/dl. Initial treatment, based on European recommendations, included Atorvastatin 20 mg and Ezetimibe 10 mg and led to a decrease in LDL-C by 46% for 5 months; however, the patient developed severe statin intolerance. Atorvastatin was replaced with Rosuvastatin 10 mg, but the symptoms persisted. Success was achieved by switching to an intermittent regimen: Rosuvastatin 10 mg three times a week with a daily intake of Ezetimibe 10 mg. However, the results were far from the desired LDL target. LDL-apheresis was advisable, but unfortunately, it is not performed in Bulgaria. In May 2017, a genetic analysis [two pathological mutations within the LDLR gene: c.1519A>G; p.(Lys507Glu) and c.2403_2406del; p.(Leu802Alafs*126)] confirmed the initial diagnosis: the patient had homozygous FH with compound heterozygosity indeed. Having turned 12 in September 2017, the patient was eligible for treatment with a PCSK9i: Evolocumab 140 mg. The mean reduction of LDL-C with the triple combination reached a reduction of 52.17% for the whole 2-year period. The LDL target was reached in January 2020. The triple therapy significantly reduced Apolipoprotein B by 29.16%. No statistically significant difference was found in Lp (a) levels (p > 0.05) Our clinical case demonstrates that the triple lipid-lowering combination in a patient with compound heterozygous FH is a good therapeutic option for reaching the LDL-target.

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Section: Discussionmentioning

confidence: 99%

“…In September 2017, the boy, already 12 years old, became eligible for treatment with PCSK9i (12)(13)(14). His case was reviewed by a National Committee, consisting of a cardiologist, a pediatrician, and an endocrinologist, and he was approved for adjuvant biweekly treatment with Evalocomab 140 mg with the consent of his parent.…”

Section: Treatment Approachmentioning

confidence: 99%

Case Report: Difficulties in the Treatment of a 12-Year-Old Patient With Homozygous Familial Hypercholesterolemia, Compound Heterozygous Form − 5 Years Follow-Up

Vladimirova-Kitova

Kitov²,

Ganev

et al. 2021

Front. Cardiovasc. Med.

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“…Among the various inflammatory drivers in COVID-19, interleukin (IL)-6 has emerged as a major contributor, with elevated levels of IL-6 being predictive of a more severe disease course 4 . Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme known for its role in regulating low-density lipoprotein (LDL) receptors, and it has been associated with vascular inflammation 5 . During acute inflammation, there is an accumulation of oxidized LDL and apolipoprotein B, which leads to the generation of cholesterol crystals in macrophages.…”

Section: Introductionmentioning

confidence: 99%

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

Arsh,

Manoj Kumar,

Simran

et al. 2024

Annals of Medicine &Amp; Surgery

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The potential role of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, we review the rationale and potential implications of PCSK9 inhibition during the inflammatory stage of SARS-CoV-2 infection. Severe cases of COVID-19 are characterized by an uncontrolled inflammatory response, often referred to as the cytokine storm, which can lead to widespread tissue damage and organ failure. Preclinical studies suggest that PCSK9 inhibition could dampen this inflammatory cascade by reducing the production of pro-inflammatory cytokines. Additionally, PCSK9 inhibition may protect against acute respiratory distress syndrome (ARDS) through its effects on lung injury and inflammation. COVID-19 has been linked to an increased risk of cardiovascular complications, especially in patients with pre-existing cardiovascular conditions or dyslipidemia. PCSK9 inhibitors are known for their ability to lower LDL cholesterol levels by enhancing the recycling of LDL receptors in the liver. By reducing LDL cholesterol, PCSK9 inhibition might protect blood vessels from further damage and lower the risk of atherosclerotic plaque formation. Moreover, PCSK9 inhibitors have shown potential antithrombotic effects in preclinical studies, making them a potential avenue to mitigate the increased risk of coagulation disorders and thrombotic events observed in COVID-19. While the potential implications of PCSK9 inhibition are promising, safety considerations and possible risks need careful evaluation. Hypocholesterolemia, drug interactions, and long-term safety are some of the key concerns that should be addressed. Clinical trials are needed to establish the efficacy and safety of PCSK9 inhibitors in COVID-19 patients and to determine the optimal timing and dosing for treatment. Future research opportunities encompass investigating the immune response, evaluating long-term safety, exploring combination therapy possibilities, and advancing personalized medicine approaches. Collaborative efforts from researchers, clinicians, and policymakers are essential to fully harness the therapeutic potential of PCSK9 inhibition and translate these findings into meaningful clinical outcomes.

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“… 14 Moreover, monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown great promise in further reducing LDL-C levels when added to statin therapy. 15 However, despite the availability of various cholesterol-lowering treatments, a significant proportion of patients do not reach their LDL-C targets. Poor adherence to statin therapy is a primary reason for this, with statin-associated muscle symptoms (SAMS) being the leading cause of treatment discontinuation.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Bempedoic Acid in Patients with Hyperlipidemia and Non-Alcoholic Fatty Liver Disease

Nisar,

Sohail,

Fatima

et al. 2024

Journal of Community Hospital Internal Medicine Perspectives

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Hyperlipidemia and its association with cardiovascular diseases have been significant public health concerns for many decades. Statins have long been the primary therapeutic option for lowering cholesterol levels and reducing cardiovascular mortality. However, a substantial number of patients either do not achieve optimal lipid goals with maximally tolerated statin doses or experience statin intolerance. In recent years, there have been remarkable developments in the field of hyperlipidemia management, leading to the approval of novel hypolipidemic drugs in North America and Europe. This article reviews the clinical development of bempedoic acid, a promising new drug, alone and in combination with ezetimibe, as an alternative approach to managing hyperlipidemia. The Phase I trials established the safety and tolerability of bempedoic acid, paving the way for further investigation in Phase II and Phase III trials. Multiple phase II studies evaluated the lipid-lowering efficacy of bempedoic acid as monotherapy or in combination with other hypolipidemic agents, showing significant improvements in lipid levels and inflammatory markers. The recently approved fixed drug combination of bempedoic acid and ezetimibe presents a viable option for patients who need additional LDL-C lowering alongside dietary modifications and maximally tolerated statin therapy.

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Modern Lipid Management: A Literature Review

Abstract: Malik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cited by 3 publications

References 30 publications

Case Report: Difficulties in the Treatment of a 12-Year-Old Patient With Homozygous Familial Hypercholesterolemia, Compound Heterozygous Form − 5 Years Follow-Up

Case Report: Difficulties in the Treatment of a 12-Year-Old Patient With Homozygous Familial Hypercholesterolemia, Compound Heterozygous Form − 5 Years Follow-Up

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review

Efficacy and Safety of Bempedoic Acid in Patients with Hyperlipidemia and Non-Alcoholic Fatty Liver Disease

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