Lipid-Lowering Drugs

• What is the name of the investigational drug that inhibits adenosine triphosphate citrate lyase?

  Bempedoic acid
• What is the mechanism of action (MOA) of Bempedoic acid?

  It inhibits adenosine triphosphate citrate lyase
• In which condition is Bempedoic acid clinically used?

  Heterozygous familial hypercholesterolemia
• What are the adverse effects associated with Bempedoic acid?

  Hyperuricemia, gout, myalgia, arthralgia
• What are the names of the PCSK9 inhibitors mentioned?

  Alirocumab and Evolocumab
• What is the relationship between PCSK9 levels and cardiovascular outcomes?

  Elevated PCSK9 levels worsen cardiovascular outcomes
• How is PCSK9 inhibitor administered?

  Subcutaneously
• What is the clinical use of PCSK9 inhibitors?

  Primary prevention in familial hypercholesterolemia
• What is the baseline LDL level for patients to be treated with PCSK9 inhibitors?

  Greater than 190 mg/dL
• What is the clinical use of Lomitapide?

  Adjunct treatment for homozygous FH
• What are common adverse effects of Lomitapide?

  Gastrointestinal disturbances
• What is the mechanism of action of Lomitapide?

  It inhibits microsomal triglyceride transport protein
• What are the names of the antisense oligonucleotides mentioned?

  Mipomersen and Volanesorsen
• What is the mechanism of action of Volanesorsen?

  It inhibits the production of apoC-III
• What condition is treated with Volanesorsen?

  Familial chylomicron syndrome
• What is a notable adverse effect of Volanesorsen?

  Thrombocytopenia
• What are the main investigational drugs for cholesterol management?

  • Bempedoic acid
  • PCSK9 inhibitors (Alirocumab, Evolocumab)
  • MTP inhibitors (Lomitapide)
  • Antisense oligonucleotides (Mipomersen, Volanesorsen)
• What are the mechanisms of action for the investigational drugs mentioned?

  • Bempedoic acid: Inhibits ATP citrate lyase
  • PCSK9 inhibitors: Antibodies to PCSK9
  • MTP inhibitors: Inhibit microsomal triglyceride transport protein
  • Antisense oligonucleotides: Inhibit production of apoC-III
• What are the clinical uses of the investigational drugs?

  • Bempedoic acid: Heterozygous familial hypercholesterolemia
  • PCSK9 inhibitors: Primary prevention in familial hypercholesterolemia
  • MTP inhibitors: Adjunct for homozygous FH
  • Antisense oligonucleotides: Familial chylomicron syndrome
• What are the common adverse effects of the investigational drugs?

  • Bempedoic acid: Hyperuricemia, gout, myalgia, arthralgia
  • PCSK9 inhibitors: Generally well-tolerated
  • MTP inhibitors: Gastrointestinal disturbances
  • Antisense oligonucleotides: Thrombocytopenia
• What is dyslipidemia primarily associated with?

  Disorders of plasma lipid transport
• What does hyperlipidaemia refer to?

  Increase in plasma lipid levels
• What conditions cause severe early-onset atherosclerosis?

  Familial Hypercholesterolaemia and Familial Type III hyperlipidaemia
• What is atherosclerosis associated with?

  Elevated LDLs, triglycerides, and low HDLs
• What do anti-hyperlipidaemic drugs prevent?

  Sequelae of atherosclerosis
• What is the importance of lipid modification therapy?

  Primary and secondary prevention of CVD
• What are the non-pharmacological treatment strategies for dyslipidemia?

  • Cardioprotective diet
  • Weight loss
  • Physical activity
  • Reduce alcohol consumption
  • Smoking cessation
• What is dyslipidemia?

  Disorders of plasma lipid transport that usually cause an increase in plasma lipid levels
• What are the consequences of familial hypercholesterolemia and familial type III hyperlipidemia?

  They cause severe early-onset atherosclerosis
• What lipid levels are associated with atherosclerosis?

  Elevated concentrations of LDLs, triglycerides, and depressed HDLs
• How do anti-hyperlipidemic drugs help patients?

  They prevent the sequelae of atherosclerosis and decrease mortality in patients with CVD and hyperlipidemia
• What is the importance of lipid modification therapy?

  It is important for the primary and secondary prevention of cardiovascular disease
• What are the non-pharmacological treatment strategies for dyslipidemia?

  • Cardioprotective diet
  • Weight loss
  • Physical activity
  • Reduce alcohol consumption
  • Smoking cessation
• What is the effect of dietary treatment on hypercholesterolemia and hypertriglyceridemia?

  Dietary treatment has a modest effect on hypercholesterolemia but is more effective for hypertriglyceridemia
• Why are lifestyle changes difficult to achieve in practice?

  Because of this, doctors tend to prescribe many drugs to control cardiovascular risk factors
• What are the three main factors that regulate plasma lipoprotein levels?

  1. Dietary fat intake, 2) Hepatic processing, and 3) Utilization in peripheral tissues
• How are lipids and cholesterol transported in the bloodstream?

  • Lipids and cholesterol are transported as complexes of lipid and protein called lipoproteins
  • Each class of lipoprotein has a specific role in lipid transport
  • There are endogenous and exogenous pathways for cholesterol transport
• What is the role of chylomicrons in the exogenous pathway of cholesterol transport?

  Chylomicrons transport cholesterol and triglycerides absorbed from the intestine to capillaries in muscles and adipose tissues
• How does ezetimibe work to lower cholesterol levels?

  Ezetimibe prevents cholesterol absorption by inhibiting the transport of cholesterol into the blood
• How do fibrates work to lower cholesterol levels?

  Fibrates enhance the activity of lipoprotein lipase