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Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

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Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
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Atherosclerosis III: Management01:26

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Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
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Dietary triglycerides from chyme in the duodenum are mixed with bile salts produced by the liver to emulsify fats. As a result, large droplets are broken down into smaller ones, increasing the surface area for enzymatic action. Once emulsified, pancreatic lipases hydrolyze the triglycerides into free fatty acids and monoglycerides.
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Lipids are an essential component of a balanced human diet. Triglycerides, which make up the majority of dietary lipids, are found in both saturated fats—commonly present in meat, dairy products, and certain tropical plants like coconut, and hydrogenated oils such as margarine and baking shortenings (trans fats)—and unsaturated fats, which are abundant in seeds, nuts, olive oil, and most vegetable oils. The main sources of cholesterol include egg yolks, various meats and organ...
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Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
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Emerging lipid lowering agents targeting LDL cholesterol.

Cezary Wójcik1

  • 1Center for Preventive Cardiology, Oregon Health and Sciences University, Portland, OR, USA.

Postgraduate Medicine
|April 4, 2020
PubMed
Summary

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death, driven by high ApoB lipoproteins. New LDL-C lowering drugs are being developed as many patients don't reach target levels with current therapies.

Keywords:
ASCVD preventionLDLPCSK9 inhibitorsbempedoic acidevinacumabgemcabeneinclisiran

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Lipid Metabolism

Background:

  • Atherosclerotic cardiovascular disease (ASCVD) is a primary cause of mortality in the US.
  • Elevated ApoB lipoproteins drive plaque formation and rupture, leading to clinical ASCVD events.
  • Low-density lipoprotein cholesterol (LDL-C) levels approximate ApoB, and current LDL-C lowering agents reduce cardiovascular risk proportionally to LDL-C reduction.

Purpose of the Study:

  • To review emerging LDL-C lowering drugs for ASCVD prevention.
  • To highlight the need for novel therapies when current treatments are insufficient.

Main Methods:

  • Review of current literature on LDL-C lowering agents.
  • Focus on new drugs including bempedoic acid, inclisiran, gemcabene, and evinacumab.
  • Exclusion of drugs targeting triglycerides, HDL-C, lipoprotein (a), inflammation, or other mechanisms.

Main Results:

  • Many patients fail to achieve recommended LDL-C levels with existing therapies (statins, ezetimibe, PCSK9 inhibitors).
  • New pharmacological agents are under development to address this unmet need.
  • These novel drugs aim to further reduce cardiovascular risk by lowering LDL-C.

Conclusions:

  • There is a significant clinical need for additional LDL-C lowering therapies.
  • Emerging drugs like bempedoic acid and inclisiran offer potential new avenues for ASCVD prevention.
  • Optimizing LDL-C reduction remains a key strategy in managing atherosclerotic cardiovascular disease.