Lipids

Lipids

Chapter 19

Objectives

  • Design therapy to treat hyperlipidemia based on guidelines.

    • Monitor therapy for efficacy, adverse drug events (ADES), contraindications (CIs).

Statins (HMG-CoA inhibitors)

  • Includes:

    • Atorvastatin

    • Rosuvastatin

    • Simvastatin

    • Lovastatin

    • Pravastatin

    • Fluvastatin

    • Pitavastatin

  • Indication:

    • Used for atherosclerotic cardiovascular disease (ASCVD) both for primary and secondary prevention.

  • Mechanism of Action (MOA):

    • Inhibits the conversion of HMG-CoA, thereby limiting cholesterol production in the liver.

    • Therapeutic Effects:

    • Decreases LDL (low-density lipoprotein), VLDL (very low-density lipoprotein), and triglycerides.

    • Causes a modest increase in HDL (high-density lipoprotein).

Statins (HMG-CoA inhibitors) - Continued

  • Contraindications (CI):

    • Pregnancy.

    • Use with extreme caution during breastfeeding.

    • Active liver disease or unexplained elevated aminotransferase level.

    • Consumption of large quantities of alcohol.

    • History of liver disease.

  • Potency Variation:

    • Statin agents differ in potency.

  • Dosing recommendations:

    • Patients with clinical ASCVD < 75 years should receive high-intensity statins like Atorvastatin or Rosuvastatin.

    • Patients with clinical ASCVD > 75 years should use moderate-intensity statins.

    • For patients with LDL-C > 190 mg/dL, high-intensity statin therapy is recommended.

Statins (HMG-CoA inhibitors) - Adverse Effects and Monitoring

  • Adverse Drug Events (ADE):

    • Myopathies, gastrointestinal issues, headaches, and elevated liver function tests (LFTs).

  • Patient Education:

    • Report any unusual muscle pain or weakness immediately.

    • Be cautious of drug interactions when other prescribers add therapy.

    • Statins should generally be taken in the evening or at bedtime as most cholesterol production occurs during sleep.

  • Monitoring:

    • Baseline LFTs and other relevant tests should be performed.

    • Repeat tests 1 to 3 months after initiating therapy, and if the expected response is achieved, monitor every 3-12 months thereafter.

Cholesterol Absorption Inhibitors

  • Includes:

    • Ezetimibe

  • Mechanism of Action (MOA):

    • Inhibits the absorption of cholesterol in the small intestine.

  • Indication:

    • Can be used as monotherapy or in combination with a statin.

  • Contraindication:

    • Sensitivity to the drug.

    • If combined with a statin, it shares the same contraindications as the statin.

  • Adverse Drug Effects (ADE):

    • Minimal effects typically include headaches, diarrhea, and abdominal pain.

    • If combined with a statin, the same ADEs as statins may occur.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9 inhibitors)

  • Includes:

    • Evolocumab

    • Alirocumab

  • Indication:

    • Add-on therapy for patients on maximally tolerated statin therapy especially in familial hypercholesterolemia.

  • Mechanism of Action (MOA):

    • Monoclonal antibodies that inhibit PCSK9, leading to substantial reductions in LDL levels.

  • Contraindication:

    • Hypersensitivity to the agents.

  • Adverse Drug Effects (ADE):

    • Long-term safety data are not yet available.

    • Common issues include nasopharyngitis and local injection-site reactions.

  • Monitoring:

    • Aim for LDL < 25 mg/dL on two separate occasions to adjust therapy intensity.

Bile Acid Resins

  • Includes:

    • Cholestyramine

    • Colestipol

    • Colesevelam

  • Indication:

    • Adjunctive therapy for patients who do not achieve the desired LDL response to maximum tolerated statin and ezetimibe therapy.

  • Mechanism of Action (MOA):

    • Binds bile acids in the intestines, promoting their excretion in feces.

  • Contraindications (CI):

    • Fasting triglycerides > 300 mg/dL.

    • Biliary obstruction.

    • Chronic constipation.

  • Adverse Drug Effects (ADE):

    • Minimal effects which can include gastrointestinal issues such as flatulence, bloating, abdominal pain, heartburn, and constipation.

    • Colesevelam generally has the least gastrointestinal ADEs.

  • Patient Education:

    • These should be taken with a meal for optimal effectiveness.

    • Avoid taking with carbonated beverages and at the same time as levothyroxine, certain antibiotics, or lipid-soluble vitamins.

Niacin

  • Mechanism of Action (MOA):

    • Decreases VLDL synthesis in the liver.

    • Inhibits lipolysis in adipose tissue and increases lipoprotein lipase activity, leading to decreased triglycerides and LDL.

  • Dosage:

    • To minimize ADEs, it is essential to titrate the dosage gradually.

    • Sustained-release forms are associated with less flushing.

  • Contraindications (CI):

    • Hepatic dysfunction.

    • Severe hypotension.

    • Persistent hyperglycemia.

    • Acute gout.

    • New-onset atrial fibrillation.

    • Not recommended as first-line treatment for patients with diabetes.

  • Adverse Drug Events (ADE):

    • Commonly reported ADEs include pruritus and flushing.

    • Aspirin (ASA) taken 30 minutes prior to administration can help reduce flushing reactions.

Fibric Acid Derivatives

  • Includes:

    • Gemfibrozil

    • Fenofibrate

  • Indication:

    • Used for severely elevated triglyceride levels.

  • Mechanism of Action (MOA):

    • Stimulates lipoprotein lipase, enhancing the breakdown of VLDL.

  • Contraindications (CI):

    • History of gallstones.

    • Severe hepatic or renal dysfunction.

    • Pregnancy has not been studied; use only if the benefit outweighs risks.

  • Adverse Drug Effects (ADE):

    • Predominantly gastrointestinal: epigastric pain, nausea, vomiting, dyspepsia, flatulence, and constipation.

    • Myopathy may occur if combined with statin therapy.

  • Drug Interactions:

    • Can enhance the effects of anticoagulants.

    • Risk of myopathies increases when using simvastatin together.

Adenosine Triphosphate-Citrate Lyase Inhibitors (ACL)

  • Includes:

    • Bempedoic acid (also available in combination with ezetimibe)

  • Indication:

    • Indicated for hyperlipidemia in patients with a history of heterogeneous familial hypercholesterolemia or established ASCVD requiring additional lowering of LDL.

  • Mechanism of Action (MOA):

    • Inhibition of ACL, thereby inhibiting cholesterol synthesis in the liver.

  • Contraindications (CI):

    • None specified.

  • Adverse Drug Events (ADE):

    • May include upper respiratory infections (URI), bronchitis, muscle spasms, back pain, abdominal pain, anemia, and elevated liver enzymes.

    • Potential for tendon rupture/injury and hyperuricemia.

  • Drug Interactions:

    • When administered with simvastatin or pravastatin, there is an increased risk of myopathies.