Hyperlipidemia Pharmacotherapy Quiz
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Questions and Answers

What is the primary mechanism of action for statin therapy?

  • Inhibit HMG-CoA reductase, reducing cholesterol synthesis (correct)
  • Inhibit VLDL synthesis in the liver
  • Increase LDL receptor availability
  • Activate PPARs to lower triglycerides

    • Which of the following is NOT a common side effect of statin therapy?

  • Injection site reactions (correct)
  • Liver enzyme elevation
  • Myopathy
  • Diabetes risk

    • What is the primary indication for PCSK9 inhibitors?

  • Hypertriglyceridemia
  • Mixed dyslipidemia
  • Elevated HDL levels
  • Familial hypercholesterolemia (correct)

    • Which lifestyle modification is recommended to improve lipid levels?

    <p>Aim for 150 minutes of moderate aerobic exercise weekly</p> Signup and view all the answers

    What side effect is commonly associated with niacin therapy?

    <p>Flushing and pruritus</p> Signup and view all the answers

    Fibrates primarily impact which type of lipids?

    <p>Decrease triglycerides and increase HDL</p> Signup and view all the answers

    What substance do PCSK9 inhibitors increase in the body?

    <p>LDL receptors</p> Signup and view all the answers

    Which of the following is true regarding fibrate therapy?

    <p>It can be used in combination with statins</p> Signup and view all the answers

    What is the recommended high-intensity statin therapy for adults at high risk (≥ 20%)?

    <p>High-intensity statin</p> Signup and view all the answers

    What should adults aiming for cardiovascular health include in their diet?

    <p>Increase vegetables and fruits</p> Signup and view all the answers

    What is the goal for weekly moderate-intensity aerobic physical activity?

    <p>150 minutes</p> Signup and view all the answers

    What is the maximum recommended weekly aerobic physical activity for vigorous-intensity exercise?

    <p>75 minutes</p> Signup and view all the answers

    The routine monitoring of liver enzymes for statin users is recommended by the FDA.

    <p>False</p> Signup and view all the answers

    The enzyme _____ is inhibited by grapefruit juice, affecting statin metabolism.

    <p>CYP3A4</p> Signup and view all the answers

    Statins cause a small but clinically insignificant increase in _____ levels.

    <p>A1c</p> Signup and view all the answers

    What is the Friedewald Equation used for calculating?

    <p>LDL</p> Signup and view all the answers

    What is the normal range for LDL cholesterol?

    <p>&lt; 100 mg/dl</p> Signup and view all the answers

    Which of the following is a key risk factor for cardiovascular disease (CVD)?

    <p>All of the above</p> Signup and view all the answers

    What is considered high-intensity statin therapy?

    <p>Rosuvastatin 20-40 mg or Atorvastatin 40-80 mg</p> Signup and view all the answers

    Which statin is considered low-intensity?

    <p>Atorvastatin 10 mg</p> Signup and view all the answers

    High levels of triglycerides are considered a significant risk factor for cardiovascular disease.

    <p>True</p> Signup and view all the answers

    How many years of diabetes is considered a risk factor for ASCVD?

    <p>10 years for T2DM, 20 years for T1DM</p> Signup and view all the answers

    Match the following drug therapies to their expected outcomes:

    <p>High-Intensity Statin = Reduce LDL by ≥ 50% Moderate-Intensity Statin = Reduce LDL by 30-50% Ezetimibe = Lower LDL if added to statin therapy PCSK9 Inhibitor = Add in cases of very high-risk ASCVD</p> Signup and view all the answers

    The equation for Non-HDL cholesterol is ______.

    <p>Total cholesterol - HDL</p> Signup and view all the answers

    What is the recommended physical activity goal for cardiovascular disease prevention?

    <p>150 minutes/week</p> Signup and view all the answers

    It is recommended to stop statins if a patient experiences a small but insignificant increase in A1c.

    <p>False</p> Signup and view all the answers

    Statins cause a small but clinically insignificant increase in ______.

    <p>A1c</p> Signup and view all the answers

    What is the risk percentage indicating adults at high risk for cardiovascular diseases?

    <p>≥ 20%</p> Signup and view all the answers

    What is the significance of HDL levels and which condition is indicated by an ABI < 0.9?

    <p>Ankle-brachial index indicates peripheral artery disease.</p> Signup and view all the answers

    What should be avoided with all statins?

    <p>Grapefruit juice</p> Signup and view all the answers

    How do you calculate LDL using the Friedewald Equation?

    <p>LDL = Total cholesterol - HDL - (TG/5)</p> Signup and view all the answers

    What are the 10-year risk factors for ASCVD?

    <p>Age, gender, race, blood pressure, total cholesterol, HDL, LDL, history of diabetes, smoking.</p> Signup and view all the answers

    Which statin benefit groups were described in the 2018 ACC/AHA Cholesterol Guidelines? (Select all that apply)

    <p>Adults 40-75 years with diabetes</p> Signup and view all the answers

    What type of statins are recognized as low-, moderate-, and high-intensity statins? (Select all that apply)

    <p>Atorvastatin 40-80 mg</p> Signup and view all the answers

    What is statin intolerance?

    <p>The inability to tolerate statin therapy due to adverse effects.</p> Signup and view all the answers

    What is the primary function of triglycerides?

    <p>Storing energy</p> Signup and view all the answers

    The Friedewald equation used to calculate LDL cholesterol is ___ .

    <p>LDL = Total cholesterol - HDL - (TG/5)</p> Signup and view all the answers

    What is considered a desirable LDL level?

    <p>&lt; 100 mg/dl</p> Signup and view all the answers

    Which of the following conditions are classified as risk factors for cardiovascular disease? (Select all that apply)

    <p>Cigarette smoking</p> Signup and view all the answers

    What lifestyle modifications are recommended for patients with hyperlipidemia?

    <p>Diet changes, regular exercise, weight management, and avoiding tobacco.</p> Signup and view all the answers

    What is the recommendation for adults 20-75 yo with LDL ≥ 190 mg/dl?

    <p>High-intensity statin therapy</p> Signup and view all the answers

    What is the mechanism of action of ezetimibe?

    <p>Inhibits cholesterol absorption at the brush border of the small intestine by targeting the NPC1L1 receptor.</p> Signup and view all the answers

    What is the impact of non-statin therapies on LDL, HDL, and TG?

    <p>Non-statin therapies can help reduce LDL and triglycerides, and may influence HDL levels.</p> Signup and view all the answers

    What is the relationship between non-statin therapies and ASCVD outcomes?

    <p>Non-statin therapies can improve ASCVD outcomes.</p> Signup and view all the answers

    What is the recommended order of use for non-statin therapies in the four statin benefit groups?

    <p>The order of use will vary by patient population and their specific conditions.</p> Signup and view all the answers

    What are key components in the definition of persistent hypertriglyceridemia?

    <p>Persistent hypertriglyceridemia is generally defined by triglyceride levels greater than 150 mg/dl over time.</p> Signup and view all the answers

    List common secondary causes of hypertriglyceridemia.

    <p>Common causes include diabetes, obesity, high carbohydrate intake, and certain medications.</p> Signup and view all the answers

    Which patient populations are likely to benefit from icosapent ethyl? (Select all that apply)

    <p>Adults ≤ 75 years with clinical ASCVD</p> Signup and view all the answers

    What is the outcome of adding ezetimibe to simvastatin?

    <p>Adding ezetimibe to simvastatin reduced major adverse cardiovascular events (MACE).</p> Signup and view all the answers

    What is the mechanism of action of PCSK9 inhibitors?

    <p>PCSK9 inhibitors block the binding of PCSK9 to LDL receptors, increasing LDL receptor recycling and lowering plasma LDL levels.</p> Signup and view all the answers

    What is the primary outcome measured in studies involving PCSK9 inhibitors?

    <p>The primary outcome is the composite of cardiovascular death, myocardial infarction (MI), cerebral vascular accident (CVA), and hospitalization for unstable angina.</p> Signup and view all the answers

    What is the primary mechanism of action of bempedoic acid?

    <p>Inhibits hepatic cholesterol biosynthesis</p> Signup and view all the answers

    Which of the following therapies primarily targets the NPC1L1 receptor?

    <p>Ezetimibe</p> Signup and view all the answers

    What is the effect of non-statin therapies on HDL levels?

    <p>Non-statin therapies have no significant effect on HDL</p> Signup and view all the answers

    What is a key component of persistent hypertriglyceridemia definition?

    <p>Triglyceride levels consistently &gt; 200 mg/dl</p> Signup and view all the answers

    Which patient population is most likely to benefit from incilisiran therapy?

    <p>Adults ≤ 75 with clinical ASCVD</p> Signup and view all the answers

    What is one of the common secondary causes of hypertriglyceridemia?

    <p>Hypothyroidism</p> Signup and view all the answers

    Which of the following therapies is known to inhibit cholesterol absorption?

    <p>Ezetimibe</p> Signup and view all the answers

    What type of therapy is icosapent ethyl classified as?

    <p>Omega-3 fatty acid therapy</p> Signup and view all the answers

    What is the recommended usage order for non-statin therapies in patients with high cholesterol?

    <p>Ezetimibe, PCSK9 mAb, Icosapent ethyl</p> Signup and view all the answers

    What is the impact of non-statin therapies on triglyceride levels?

    <p>Some non-statin therapies may decrease triglyceride levels</p> Signup and view all the answers

    What was the primary outcome defined in the study involving Simvastatin and Ezetimibe?

    <p>Composite of CV death, nonfatal MI, nonfatal CVA, UA w hospitalization, coronary revascularization</p> Signup and view all the answers

    What effect did the addition of Ezetimibe to Simvastatin have on the primary outcome percentage?

    <p>Reduced it from 32.7% to 34.7%</p> Signup and view all the answers

    What was the percentage of nonfatal MI observed in patients taking Simvastatin alone?

    <p>14.4%</p> Signup and view all the answers

    How did Evolocumab impact the primary endpoint compared to placebo?

    <p>It decreased the event rate.</p> Signup and view all the answers

    What was the hazard ratio (HR) for nonfatal MI when comparing Simvastatin plus Ezetimibe to Simvastatin alone?

    <p>0.87</p> Signup and view all the answers

    What is the effect of PCSK9 inhibitors on LDL receptor recycling?

    <p>They increase LDL receptor recycling and lower LDL levels.</p> Signup and view all the answers

    What was the result for ischemic CVA rates with the combination therapy of Simvastatin plus Ezetimibe?

    <p>Decreased to 3.4%</p> Signup and view all the answers

    What was the follow-up duration for the Evolocumab study?

    <p>2 years</p> Signup and view all the answers

    How did the risk of major cardiovascular events (MACE) compare between patients taking Evolocumab and those taking a placebo?

    <p>9.8% for Evolocumab vs 11.3% for placebo</p> Signup and view all the answers

    Which medication is administered as a subcutaneous injection for managing LDL levels?

    <p>Evolocumab</p> Signup and view all the answers

    What is the appropriate classification for a patient aged 46 with a 10-year ASCVD risk of 15% due to diabetes?

    <p>Moderate</p> Signup and view all the answers

    Which patient is indicated for high-intensity statin therapy based on the given criteria?

    <p>60 yo with a history of myocardial infarction</p> Signup and view all the answers

    Which option correctly identifies a secondary cause of hyperlipidemia?

    <p>Renal failure</p> Signup and view all the answers

    What is the LDL level requirement for an adult aged 40-75 with diabetes to consider statin therapy?

    <p>LDL &gt; 70 mg/dl</p> Signup and view all the answers

    How much does each 1% reduction in LDL cholesterol reduce the risk of ASCVD?

    <p>1%</p> Signup and view all the answers

    What is the correct dose range for high-intensity statin therapy using Atorvastatin?

    <p>40-80 mg</p> Signup and view all the answers

    Which of these symptoms is NOT commonly associated with statin therapy?

    <p>Chest pain</p> Signup and view all the answers

    For an individual aged 46 with an LDL of 170 mg/dl and a 10-year ASCVD risk of 15%, what type of statin therapy is recommended?

    <p>High-intensity statin</p> Signup and view all the answers

    What is the equivalent dose of Pravastatin that corresponds to Simvastatin 20 mg?

    <p>10 mg</p> Signup and view all the answers

    Which factor is NOT considered when determining the 10-year ASCVD risk?

    <p>Family history of allergies</p> Signup and view all the answers

    What is the recommended statin therapy for adults ≤ 75 years old with clinical ASCVD?

    <p>High-intensity statin to reduce LDL ≥ 50%</p> Signup and view all the answers

    What is the recommendation for patients with ASCVD who are on the maximum tolerated statins but have LDL levels ≥ 70 mg/dl?

    <p>Add ezetimibe</p> Signup and view all the answers

    In which scenario should a moderate-intensity statin be considered for patients with HFrEF?

    <p>If the patient has a reasonable life expectancy of 3-5 years</p> Signup and view all the answers

    What is the recommendation for adults over 75 years old with clinical ASCVD who are already tolerating high-intensity statin therapy?

    <p>Continue high-intensity statin</p> Signup and view all the answers

    What should be added for adults ≤ 75 years old with very high-risk ASCVD on maximum tolerated statin therapy with LDL ≥ 70 mg/dl?

    <p>Ezetimibe</p> Signup and view all the answers

    For patients with very high-risk ASCVD who are on maximum tolerated LDL-lowering therapy, which therapy can be added?

    <p>PCSK9 inhibitor</p> Signup and view all the answers

    Which factor would classify a patient as very high-risk for ASCVD?

    <p>Recent ACS within the past 12 months</p> Signup and view all the answers

    Which of the following is a high-risk condition contributing to ASCVD risk classification?

    <p>Hypertension</p> Signup and view all the answers

    What should be the LDL target for patients with very high-risk ASCVD to consider additional therapy?

    <p>LDL ≥ 70 mg/dl</p> Signup and view all the answers

    What recommendation applies to patients who have multiple major ASCVD events?

    <p>High-intensity statin therapy is necessary</p> Signup and view all the answers

    What is the primary function of LDL in the body?

    <p>Carrier of cholesterol</p> Signup and view all the answers

    What is considered a significant risk factor for developing ASCVD?

    <p>Smoking cigarettes</p> Signup and view all the answers

    Which of the following is NOT one of the 4 statin benefit groups outlined in the 2018 ACC/AHA guidelines?

    <p>Individuals above age 60 with high triglycerides</p> Signup and view all the answers

    What does an increased level of Apolipoprotein B (ApoB) indicate?

    <p>Increased atherogenicity</p> Signup and view all the answers

    Which class of lipoprotein is primarily responsible for carrying triglycerides?

    <p>VLDL</p> Signup and view all the answers

    What lifestyle modification is recommended for individuals with hyperlipidemia?

    <p>Adopting a balanced diet with low saturated fats</p> Signup and view all the answers

    What defines statin intolerance?

    <p>Experiencing significant adverse effects from statin therapy</p> Signup and view all the answers

    Which method is used to calculate Non-HDL cholesterol?

    <p>Total cholesterol - HDL cholesterol</p> Signup and view all the answers

    What is a significant side effect that has a very low incidence in statin therapy?

    <p>Severe liver injury</p> Signup and view all the answers

    Which of the following should be avoided due to interaction effects with statins?

    <p>Grapefruit juice</p> Signup and view all the answers

    What lifestyle modification is recommended in conjunction with statin use to promote cardiovascular health?

    <p>Regular physical activity</p> Signup and view all the answers

    What is the recommendation regarding routine monitoring of liver enzymes for patients on statins?

    <p>Only baseline monitoring is required</p> Signup and view all the answers

    For adults with an LDL level between 70 and 189 mg/dl and at intermediate risk of cardiovascular disease, what is the recommended therapy?

    <p>Moderate-intensity statin</p> Signup and view all the answers

    What is the recommendation for adults aged 20-75 years with an LDL level of 190 mg/dl or higher?

    <p>High-intensity statin therapy</p> Signup and view all the answers

    For adults aged 40-75 years with diabetes and multiple ASCVD risk factors, what is the recommended treatment?

    <p>High-intensity statin</p> Signup and view all the answers

    If an adult on maximum tolerated statin therapy has LDL levels greater than 100 mg/dl and inadequate reduction, what should be added?

    <p>Ezetimibe</p> Signup and view all the answers

    What is considered a normal fasting LDL cholesterol level?

    <p>&lt; 100 mg/dl</p> Signup and view all the answers

    What therapy is recommended for adults 30-75 years with heterozygous familial hypercholesterolemia (HeFH) and LDL > 100 mg/dl?

    <p>Add a PCSK9 inhibitor</p> Signup and view all the answers

    What is the LDL target for adults with diabetes who have a 10-year ASCVD risk of 20% or greater?

    <p>No specific target</p> Signup and view all the answers

    In adults 20-39 years old, which of the following is considered a diabetes-specific risk enhancer?

    <p>Long duration of diabetes</p> Signup and view all the answers

    Which drug is recommended to be added if an adult on maximal statin therapy shows less than 50% reduction in LDL?

    <p>Ezetimibe</p> Signup and view all the answers

    What should be considered for young adults (20-39 years) with diabetes regarding statin therapy?

    <p>Consider moderate-intensity statin therapy</p> Signup and view all the answers

    What is the recommendation for adults 40-75 years who have an ASCVD risk of 20% or greater?

    <p>High-intensity statin therapy</p> Signup and view all the answers

    What is the recommended LDL target for patients with very high-risk ASCVD?

    <p>&lt; 70 mg/dl</p> Signup and view all the answers

    What is the first line of treatment for high-risk patients with diabetes and an LDL level ≥ 190 mg/dl?

    <p>High-intensity statin</p> Signup and view all the answers

    In patients with borderline diabetes, what is the recommended statin intensity?

    <p>Moderate</p> Signup and view all the answers

    For patients with persistent hypertriglyceridemia, what second-line therapy may be added?

    <p>Icosapent ethyl</p> Signup and view all the answers

    Which approach is recommended for patients with a 10-year ASCVD risk between 7.5% and 20%?

    <p>Consider statin therapy if risk factors are present</p> Signup and view all the answers

    Which medication is typically not included as a second-line option after statin therapy in managing ASCVD risk?

    <p>Niacin</p> Signup and view all the answers

    What percentage of LDL reduction is targeted for patients with an LDL level ≥ 220 mg/dl?

    <p>≥ 50%</p> Signup and view all the answers

    What first-line therapy is indicated for patients at risk for ASCVD events who have multiple risk factors?

    <p>High-intensity statins</p> Signup and view all the answers

    What additional therapy can be considered after ezetimibe for patients with high ASCVD risk?

    <p>PCSK9 mAb</p> Signup and view all the answers

    Which natural product is commonly used for cholesterol lowering?

    <p>Red Yeast Rice</p> Signup and view all the answers

    What is one of the main benefits of garlic in relation to cholesterol?

    <p>Reduces LDL cholesterol</p> Signup and view all the answers

    Which of the following statements about garlic is false?

    <p>Garlic has no impact on cholesterol levels.</p> Signup and view all the answers

    Which of the following is not a natural product used for cholesterol lowering?

    <p>St. John's Wort</p> Signup and view all the answers

    What is the primary function attributed to garlic concerning cholesterol?

    <p>Reduce serum lipids</p> Signup and view all the answers

    Which of the following best describes persistent hypertriglyceridemia?

    <p>A consistent elevation of triglyceride levels beyond normal ranges over time.</p> Signup and view all the answers

    What triglyceride level is typically considered indicative of persistent hypertriglyceridemia?

    <p>200 mg/dL or higher</p> Signup and view all the answers

    Which of the following can contribute to persistent hypertriglyceridemia?

    <p>Chronic kidney disease</p> Signup and view all the answers

    Persistent hypertriglyceridemia is primarily associated with an increased risk for which condition?

    <p>Cardiovascular disease</p> Signup and view all the answers

    Which factor is least likely to lead to persistent hypertriglyceridemia?

    <p>Ideally monitored cholesterol levels</p> Signup and view all the answers

    What is the primary mechanism of action for PCSK9 inhibitors?

    <p>Prevent PCSK9 from degrading LDL receptors</p> Signup and view all the answers

    Which side effect is most commonly associated with the use of Niacin?

    <p>Flushing and pruritus</p> Signup and view all the answers

    What do studies suggest about the efficacy of PCSK9 inhibitors compared to statins?

    <p>They often surpass statin efficacy in specific high-risk groups</p> Signup and view all the answers

    Which patient group is recommended to use non-statin therapies?

    <p>Patients who are statin intolerant</p> Signup and view all the answers

    Which non-statin therapy has been shown to reduce cardiovascular events when added to statins?

    <p>Ezetimibe</p> Signup and view all the answers

    What underlies the mechanism of action for fibrates?

    <p>They activate peroxisome proliferator-activated receptors</p> Signup and view all the answers

    What is a common side effect of bile acid sequestrants?

    <p>Gastrointestinal discomfort</p> Signup and view all the answers

    What differentiates the benefit of PCSK9 inhibitors from fibrates?

    <p>PCSK9 inhibitors have a substantial impact on LDL-C reduction</p> Signup and view all the answers

    What is a potential risk factor when using fibrates?

    <p>Gastrointestinal upset and myopathy</p> Signup and view all the answers

    What is the primary effect of bile acid sequestrants on cholesterol levels?

    <p>Decrease circulating LDL cholesterol levels</p> Signup and view all the answers

    Which of the following is a common side effect associated with bile acid sequestrants?

    <p>Constipation</p> Signup and view all the answers

    How does the effectiveness of bile acid sequestrants compare to that of statins in reducing LDL cholesterol?

    <p>They are generally less effective than statins</p> Signup and view all the answers

    What is a long-term outcome associated with the use of bile acid sequestrants?

    <p>Modest risk reduction for cardiovascular events</p> Signup and view all the answers

    Ideal candidates for bile acid sequestrant therapy include which of the following?

    <p>Patients who are statin-intolerant</p> Signup and view all the answers

    What mechanism leads to increased LDL cholesterol reduction when using bile acid sequestrants?

    <p>Increased conversion of cholesterol into bile acids</p> Signup and view all the answers

    Which of the following is a less common side effect of bile acid sequestrants?

    <p>Malabsorption of fat-soluble vitamins</p> Signup and view all the answers

    What potential issue may arise from long-term use of bile acid sequestrants?

    <p>Increased triglyceride levels</p> Signup and view all the answers

    Which factor should be considered when selecting patients for bile acid sequestrant therapy?

    <p>Unexpected medication interactions</p> Signup and view all the answers

    What is the primary mechanism of action of bempedoic acid?

    <p>Inhibits ATP-citrate lyase</p> Signup and view all the answers

    Which side effect is associated with non-statin therapies?

    <p>Gout risk</p> Signup and view all the answers

    What is the expected LDL cholesterol reduction from bempedoic acid when used as monotherapy?

    <p>15-20%</p> Signup and view all the answers

    Which lipid-lowering agent is considered the most potent for LDL reduction?

    <p>PCSK9 inhibitors</p> Signup and view all the answers

    What is the standard first-line therapy for individuals at high risk for cardiovascular events?

    <p>Statins</p> Signup and view all the answers

    What is a serious side effect associated with the use of non-statin therapies?

    <p>Liver enzyme elevation</p> Signup and view all the answers

    Which of the following statements is true regarding the combination therapy of bempedoic acid?

    <p>It provides greater lipid control compared to statins alone.</p> Signup and view all the answers

    What is one of the primary considerations for patients not achieving lipid targets with statins?

    <p>Adding bempedoic acid or other non-statin therapies</p> Signup and view all the answers

    Which common gastrointestinal side effects might be experienced with non-statin therapies?

    <p>Nausea</p> Signup and view all the answers

    When assessing a patient for hyperlipidemia management, what is the importance of lifestyle modifications?

    <p>They form the foundation of treatment.</p> Signup and view all the answers

    What is the primary mechanism of action of inclisiran?

    <p>Inhibition of PCSK9 protein</p> Signup and view all the answers

    Which of the following reflects inclisiran's clinical efficacy?

    <p>It shows effectiveness in patients with statin intolerance.</p> Signup and view all the answers

    How does inclisiran differ from statins in terms of side effects?

    <p>Inclisiran has a favorable safety profile with fewer muscle-related side effects.</p> Signup and view all the answers

    Which patient group is most suitable for inclisiran therapy?

    <p>Patients with familial hypercholesterolemia who are at high cardiovascular risk.</p> Signup and view all the answers

    What is a common side effect associated with inclisiran therapy?

    <p>Injection site reactions like pain or redness.</p> Signup and view all the answers

    What is the primary effect of ANGPTL3 inhibition on triglyceride levels?

    <p>Decreases triglyceride levels</p> Signup and view all the answers

    Which of the following trials evaluated the efficacy of Evinacumab?

    <p>Evince</p> Signup and view all the answers

    How do ANGPTL3 inhibitors primarily affect lipid metabolism?

    <p>By inhibiting lipoprotein lipase (LPL)</p> Signup and view all the answers

    What is indicated regarding the comparative effectiveness of ANGPTL3 inhibitors?

    <p>They can achieve greater lipid lowering compared to traditional therapies.</p> Signup and view all the answers

    Which common side effect is associated with ANGPTL3 inhibitors?

    <p>Injection-site reactions</p> Signup and view all the answers

    What classification indicates that a treatment is not beneficial and may be harmful?

    <p>Class III</p> Signup and view all the answers

    Which group should be considered for moderate intensity statin therapy?

    <p>Adults aged 40–75 with an LDL-C of 70-189 mg/dL and ASCVD risk of 5% to &lt;20%</p> Signup and view all the answers

    What is the primary goal of cholesterol management?

    <p>Lower LDL-C levels</p> Signup and view all the answers

    Which population is prioritized for statin therapy initiation?

    <p>Adults aged 40–75 with elevated LDL-C levels</p> Signup and view all the answers

    What percentage indicates high risk for a 10-year ASCVD event in adults aged 40-75 for statin therapy initiation?

    <p>20% or higher</p> Signup and view all the answers

    Which lifestyle modification is part of non-pharmacological approaches for cholesterol management?

    <p>Regular physical activity</p> Signup and view all the answers

    What is the criteria for high-intensity statin therapy based on ASCVD history?

    <p>History of cardiovascular disease</p> Signup and view all the answers

    In which category are treatments with conflicting evidence regarding usefulness categorized?

    <p>Class IIa</p> Signup and view all the answers

    What should occur regularly to assess the effectiveness of cholesterol therapy?

    <p>Annual lipid panel evaluations</p> Signup and view all the answers

    Which LDL-C level range necessitates treatment with statins for primary prevention?

    <p>70-189 mg/dL</p> Signup and view all the answers

    What is the primary endpoint typically measured in clinical trials assessing triglyceride therapies?

    <p>Change in triglyceride levels</p> Signup and view all the answers

    Which non-statin therapy is known for specifically lowering triglyceride levels?

    <p>Omega-3 Fatty Acids</p> Signup and view all the answers

    Which dietary change is recommended for managing hypertriglyceridemia?

    <p>Consume more healthy fats</p> Signup and view all the answers

    What is the recommended treatment goal for triglyceride levels in patients undergoing management?

    <p>Below 150 mg/dL</p> Signup and view all the answers

    Which of the following is NOT mentioned as an important criterion in trial population selection for triglyceride studies?

    <p>Age of participants</p> Signup and view all the answers

    What role do lifestyle modifications play in managing triglyceride levels?

    <p>They are considered the first-line therapy.</p> Signup and view all the answers

    Which of these non-statin therapies is primarily used to lower LDL cholesterol?

    <p>PCSK9 Inhibitors</p> Signup and view all the answers

    Which of the following lifestyle changes can significantly reduce triglyceride levels?

    <p>Regular exercise</p> Signup and view all the answers

    Which secondary endpoint may be evaluated in trials focusing on triglyceride lowering therapies?

    <p>Overall mortality</p> Signup and view all the answers

    What is a potential benefit of monitoring lipid panels regularly in patients with high triglycerides?

    <p>To assess treatment efficacy</p> Signup and view all the answers

    Match the clinical trial with its focus:

    <p>REDUCE-IT = Icosapent ethyl and cardiovascular event reduction VA-HIT = Fibrates and low HDL cholesterol benefits HPS2-THRIVE = Niacin and statin combination for hypertriglyceridemia HEART = Effect of lifestyle changes on lipid profiles</p> Signup and view all the answers

    Match the risk factor with its description:

    <p>Obesity = Increased triglyceride levels Diabetes mellitus = Insulin resistance leading to lipid disturbances Sedentary lifestyle = Lack of physical activity contributing to hyperlipidemia Familial hypertriglyceridemia = Genetic predisposition to high triglycerides</p> Signup and view all the answers

    Match the non-statin therapy with its main side effect:

    <p>Fibrates = Muscle-related adverse events Omega-3 Fatty Acids = Gastrointestinal symptoms Niacin = Flushing and liver toxicity PCSK9 Inhibitors = Injection site reactions</p> Signup and view all the answers

    Match the treatment guideline with its condition:

    <blockquote> <p>150 mg/dL = Initiate lifestyle modifications 500 mg/dL = Consider pharmacotherapy to prevent pancreatitis Lifestyle changes = First-line approach for lipid management Combination therapy = May include statins for better lipid control</p> </blockquote> Signup and view all the answers

    Match the outcome with the non-statin therapy:

    <p>Fibrates = Lower triglycerides, raise HDL cholesterol Omega-3 Fatty Acids = Reduces triglyceride levels Niacin = May not reduce cardiovascular risks PCSK9 Inhibitors = Lower LDL and triglycerides</p> Signup and view all the answers

    Match the patient outcome with the associated therapy:

    <p>Significant triglyceride reduction = All non-statin therapies Reduced risk of pancreatitis = Pharmacotherapy for very high triglycerides Variable cardiovascular outcomes = Some non-statin medications Improvement in HDL levels = Fibrates</p> Signup and view all the answers

    Match the medication with its type:

    <p>Fibrates = Non-statin therapy Omega-3 Fatty Acids = Nutraceutical agents Niacin = Vitamin-based therapy PCSK9 Inhibitors = Monoclonal antibodies for LDL management</p> Signup and view all the answers

    Match the trial with its specific population focus:

    <p>REDUCE-IT = Patients with high triglycerides VA-HIT = Patients with low HDL cholesterol HPS2-THRIVE = Patients with hypertriglyceridemia and statin use FOCUS = General population at risk for CVD</p> Signup and view all the answers

    Match the lifestyle modification with its benefit:

    <p>Diet = Reduces triglycerides Exercise = Improves overall lipid profile Weight loss = Lowers risk factors for hyperlipidemia Limit alcohol = Decreases triglyceride levels</p> Signup and view all the answers

    Match the following trials with their focus or treatment:

    <p>IMPROVE-IT Trial = Ezetimibe effectiveness FOURIER Trial = PCSK9 inhibitor outcomes ODYSSEY Trial = Alirocumab in hyperlipidemia CLEAR Trial = Lomitapide for HoFH</p> Signup and view all the answers

    Match the following terminology with its description:

    <p>Elipase HoFH Trial = Treatment for Homozygous Familial Hypercholesterolemia Reduce-it Trial = Icosapent ethyl effectiveness Strength Trial = Omega-3 fatty acids in cardiovascular risk Accord Lipid Trial = Intensive lipid therapy outcomes</p> Signup and view all the answers

    Match the following trials with the drug tested:

    <p>Prominent Trial = Niacin therapy Aim-High Trial = Extended-release niacin HPS2-THRIVE Trial = Niacin + laropiprant ORION Trial = Inclisiran for LDL reduction</p> Signup and view all the answers

    Match the following trials with the type of patients studied:

    <p>Reduce-it Trial = Patients with elevated triglycerides IMPROVE-IT Trial = Patients with acute coronary syndrome FOURIER Trial = Patients with atherosclerotic cardiovascular disease Strength Trial = Patients with hypertriglyceridemia</p> Signup and view all the answers

    Match the following trials with their primary outcome measure:

    <p>CLEAR Trial = LDL-C reduction Prominent Trial = Outcomes in cardiovascular events Accord Lipid Trial = Impact on cardiovascular mortality HPS2-THRIVE Trial = Rate of major vascular events</p> Signup and view all the answers

    Study Notes

    Hyperlipidemia Pharmacotherapy

    Statin Therapy

    • Mechanism of Action: Inhibit HMG-CoA reductase, reducing cholesterol synthesis in the liver.
    • Indications: Primary and secondary prevention of cardiovascular disease, elevated LDL cholesterol levels.
    • Common Statins: Atorvastatin, Rosuvastatin, Simvastatin, Lovastatin.
    • Side Effects: Myopathy, rhabdomyolysis, liver enzyme elevation, diabetes risk.
    • Monitoring: Lipid levels, liver function tests, muscle symptoms.

    PCSK9 Inhibitors

    • Mechanism of Action: Monoclonal antibodies that inhibit PCSK9 protein, increasing LDL receptor availability and lowering LDL levels.
    • Common Agents: Alirocumab, Evolocumab.
    • Indications: Familial hypercholesterolemia, statin intolerance, high cardiovascular risk.
    • Administration: Subcutaneous injection.
    • Side Effects: Injection site reactions, flu-like symptoms.

    Lifestyle Modifications

    • Dietary Changes: Increase fruits, vegetables, whole grains; reduce saturated fats, trans fats, and cholesterol.
    • Physical Activity: Aim for at least 150 minutes of moderate aerobic exercise weekly.
    • Weight Management: Maintain a healthy body weight; even modest weight loss can improve lipid levels.
    • Smoking Cessation: Quitting smoking improves HDL levels and overall cardiovascular health.

    Niacin

    • Mechanism of Action: Reduces hepatic synthesis of VLDL and LDL; increases HDL.
    • Indications: Mixed dyslipidemia, especially in patients with low HDL.
    • Side Effects: Flushing, pruritus, gastrointestinal issues, hepatotoxicity.
    • Monitoring: Liver function tests; consider dose adjustments.

    Fibrates

    • Mechanism of Action: Activate peroxisome proliferator-activated receptors (PPARs), leading to decreased triglycerides and increased HDL.
    • Common Agents: Fenofibrate, Gemfibrozil.
    • Indications: Hypertriglyceridemia, dyslipidemia; often in conjunction with statins.
    • Side Effects: Myopathy, gallstones, liver function abnormalities.
    • Monitoring: Lipid levels, liver function tests, muscle symptoms.

    Statin Therapy

    • Inhibit HMG-CoA reductase, reducing cholesterol synthesis in the liver
    • Used for primary and secondary prevention of cardiovascular disease and elevated LDL cholesterol levels
    • Common examples include Atorvastatin, Rosuvastatin, Simvastatin, and Lovastatin
    • Side effects include myopathy, rhabdomyolysis, liver enzyme elevation, and increased diabetes risk
    • Monitor lipid levels, liver function tests, and muscle symptoms.

    PCSK9 Inhibitors

    • Monoclonal antibodies inhibiting PCSK9 protein, increasing LDL receptor availability and lowering LDL levels
    • Common agents: Alirocumab, Evolocumab
    • Used for familial hypercholesterolemia, statin intolerance, and high cardiovascular risk
    • Administered via subcutaneous injection
    • Side effects include injection site reactions and flu-like symptoms.

    Lifestyle Modifications

    • Dietary changes: Increase fruits, vegetables, whole grains, and reduce saturated fats, trans fats, and cholesterol intake.
    • Physical Activity: Aim for at least 150 minutes of moderate aerobic exercise weekly.
    • Weight Management: Maintain a healthy body weight, even modest weight loss can improve lipid levels.
    • Smoking Cessation: Quitting smoking improves HDL levels and overall cardiovascular health

    Niacin

    • Reduces hepatic synthesis of VLDL and LDL, increasing HDL
    • Indicated for mixed dyslipidemia, especially in patients with low HDL
    • Side effects include flushing, pruritus, gastrointestinal issues, and hepatotoxicity
    • Monitor liver function tests and adjust dosage as needed

    Fibrates

    • Activate peroxisome proliferator-activated receptors (PPARs) leading to decreased triglycerides and increased HDL
    • Common agents include Fenofibrate and Gemfibrozil
    • Used for hypertriglyceridemia and dyslipidemia, often in conjunction with statins
    • Side effects include myopathy, gallstones, and liver function abnormalities
    • Monitor lipid levels, liver function tests, and muscle symptoms.

    Hyperlipidemia

    • ASCVD is atherosclerotic cardiovascular disease
    • LDL is the primary carrier of cholesterol
    • VLDL is the primary carrier of triglycerides
    • HDL is not atherogenic and is considered protective
    • ApoB is a strong predictor of atherogenicity and is embedded in LDL and VLDL
    • Non-HDL includes LDL and VLDL together
    • 86 million adults in the US have total cholesterol above 200 mg/dL
    • 33-36% of US adults have total cholesterol above 200 mg/dL
    • 25 million adults in the US have total cholesterol above 240 mg/dL
    • Hyperlipidemia, cigarette smoking, hypertension, diabetes, and increasing age are all risk factors for ASCVD.
    • ASCVD is the leading cause of morbidity and mortality in the US.
    • One in four deaths in the US are attributed to ASCVD

    Diagnosis and Management of Hyperlipidemia

    • A lipid profile, 10-year risk of ASCVD assessment, and evaluation for secondary causes are all part of diagnosing hyperlipidemia.
    • A lipid profile includes total cholesterol, HDL, LDL, and triglycerides.
    • The Friedewald equation is used to calculate LDL: LDL = Total cholesterol – HDL – (TG/5)
    • Non-HDL equations are used to calculate non-HDL cholesterol: Non-HDL = Total cholesterol – HDL, OR Non-HDL = LDL + TG/5
    • The American College of Cardiology (ACC) and the American Heart Association (AHA) recommend checking fasting or non-fasting lipid levels every 4-6 years for adults 20 years of age and older who are not on lipid-lowering therapy.
    • The ASCVD Risk Calculator can be used to estimate the 10-year risk of ASCVD.
    • The PREVENT Calculator can be used to estimate the 10-year and 30-year risk of ASCVD, CVD, and heart failure.
    • Adults 40-75 years of age should have their 10-year risk of ASCVD calculated using the ASCVD Risk Calculator.
    • For patients with a 10-year risk of ASCVD between 5% and 7.4%, they are considered borderline risk. Patients with a 10-year risk of ASCVD between 7.5% and 19.9% are considered intermediate risk. Patients with a 10-year risk of ASCVD ≥20% are considered high risk.

    Lifestyle Management of Hyperlipidemia

    • Lifestyle modifications for patients with hyperlipidemia include:
    • Dietary changes - avoid saturated and trans fats
    • Regular physical activity
    • Weight loss, if overweight or obese
    • Smoking cessation

    ### Drug Therapy for Hyperlipidemia

    • Statins are the first-line treatment for hyperlipidemia.
    • High-intensity statins reduce LDL cholesterol by ≥50%.
    • Moderate-intensity statins reduce LDL cholesterol by 30% to 50%.
    • Low-intensity statins reduce LDL cholesterol by 30% - 50%.
    • Statin selection depends on the patient's risk factors, ASCVD risk, and LDL cholesterol goal.
    • Ezetimibe is a cholesterol absorption inhibitor that can be added to statin therapy for further LDL reduction.
    • PCSK9 inhibitors are monoclonal antibodies that inhibit PCSK9, an enzyme that breaks down LDL. PCSK9 inhibitors are used in patients who have not achieved their LDL cholesterol goals with statin and ezetimibe therapy.
    • Bile acid sequestrants (BAS) are often used in patients with elevated triglycerides.
    • Statin intolerance is the inability to tolerate statin therapy due to adverse effects.

    Adverse Drug Reactions Associated With Statins

    • Myopathy is a common adverse effect associated with statins.
    • Rhabdomyolysis is a serious adverse effect associated with statins.

    Pharmacokinetic Properties of Statins

    • Statins are metabolized by the liver.
    • Statins are generally well-tolerated.
    • Statins are contraindicated in pregnancy and lactation.

    Statin Dose Reduction

    • Reduce or avoid simvastatin and lovastatin dosage when co-administered with P-glycoprotein (P-gp) and CYP3A4 inhibitors.
    • P-gp and CYP3A4 inhibitors include protease inhibitors, fungal azoles, cyclosporine, macrolides, amiodarone, amlodipine, non-dihydropyridine calcium channel blockers (verapamil, diltiazem).

    Lifestyle Modifications for Dyslipidemia

    • Dietary interventions for dyslipidemia include increased intake of vegetables, fruits, legumes, nuts, whole grains, fish, and mono- and polyunsaturated fats.
    • Reduce cholesterol and sodium intake.
    • Minimize processed meat, refined carbohydrates, and sweetened beverages.
    • Avoid trans fats.
    • Physical activity: Aim for 150 minutes per week of moderate-intensity aerobic activity or 75 minutes per week of vigorous-intensity aerobic activity.
    • Weight reduction, smoking cessation, and dietary modifications are also beneficial.

    ### Hyperlipidemia

    • 86 million US adults ≥ 20 yo have TC > 200 mg/dl
    • 33-36% of US adults
    • 25 million above 240 mg/dl

    ### Atherosclerosis and ASCVD

    • Atherosclerosis is a disease in which plaque builds up inside your arteries.
    • Atherosclerotic cardiovascular disease (ASCVD) is a general term for heart and blood vessel diseases caused by atherosclerosis.
    • ASCVD leading cause of morbidity and mortality for men, women, and people of most racial and ethnic groups in the US.
    • 1 in 4 deaths is caused by ASCVD.

    ### Risk Factors for ASCVD

    • Key risk factors
      • Hypertension
      • Cigarette smoking
      • Hyperlipidemia
      • Diabetes
    • Other risk factors
      • Overweight or obesity
      • Unhealthy diet
      • Physical inactivity
      • Excessive alcohol use

    Dyslipidemia & Hyperlipidemia

    • Elevated LDL
    • Elevated VLDL (TG)
    • Low HDL

    ASCVD Risk Assessment

    • Lipid profile
    • 10-year risk of ASCVD
      • Assess using the ASCVD Risk Estimator or ASCVD Plus
    • Risk Enhancing Factors
      • Family History of premature ASCVD
      • Genetic hyperlipidemia
    • Secondary causes
      • Drugs
      • Diseases

    Lipoprotein Testing

    • Fasting or non-fasting blood draws:
      • Total cholesterol
      • LDL (can be measured or calculated)
      • HDL
      • Triglycerides
    • Friedewald Equation:
      • LDL = Total cholesterol – HDL – (TG/5)
    • Non-HDL Equations:
      • Non-HDL = Total cholesterol – HDL
      • Non-HDL = LDL + TG/5

    ### LDL and Non-HDL Goals

    • LDL
      • < 100 Desirable
      • 100-129 Above desirable
      • 130-159 Borderline high
      • 160-189 High
      • ≥ 190 Very High
    • Non-HDL
      • < 130 Desirable
      • 130-159 Above desirable
      • 160-189 Borderline high
      • 190-219 High
      • ≥ 220 Very High

    ### Triglycerides and HDL Goals

    • Triglycerides
      • < 150 Normal
      • 150-199 Borderline high
      • 200-499 High
      • ≥ 500 Very High
    • HDL
      • ≥ 40 (men) Desirable
      • ≥ 50 (women) Desirable
    • Optimal Total Cholesterol: 150 mg/dl

    ### Lipid Screening Recommendations & Criteria

    • Adults ≥ 20 yo, and not on lipid-lowering therapy
      • Check fasting or non-fasting lipid levels
      • Check every 4-6 years
    • TG > 400 mg/dl, if non-fasting
      • Check fasting lipid levels
    • LDL < 70 mg/dl
      • Measure direct LDL
    • **FmHx of premature ASCVD or genetic hyperlipidemia **
      • Check fasting lipid levels

    2019 AHA/ACC Guideline on the Primary Prevention of CVD - Recommendations for Screening

    • Age 20-39 yrs
      • Assess ASCVD risk factors every 4-6 years
    • Age 40-75 yrs
      • Assess ASCVD risk factors and calculate 10-year risk of ASCVD using the ASCVD Risk Calculator
    • Adults with 10-yr risk of 5% to < 20%
      • Consider assessment of “Risk Enhancing Factors” to guide decisions about preventative interventions

    ### ASCVD Risk Estimator

    • Pooled Cohort Risk Assessment “ASCVD Risk Calculator”
      • Calculates the risk of CVD, ASCVD, and heart failure.
      • Uses cardiovascular-kidney-metabolic health.
      • Calculates a 10-year risk for patients 30-79 years old.
      • Calculates a 30-year risk for patients 30-59 years old.
      • Available on acc.org and as a mobile app: ASCVD Plus

    ### PREVENT

    • Calculates the risk of CVD, ASCVD, heart failure, and other cardiovascular related conditions.
      • Uses cardiovascular-kidney-metabolic health.
      • Calculates a 10-year risk for patients 30-79 years old.
      • Calculates a 30-year risk for patients 30-59 years old.
      • Differs from ASCVD Risk Estimator:
        • Includes BMI and eGFR.
        • Does NOT include LDL or race.
        • Optional info: UACR, HbA1c, zip code
      • Available on professional.heart.org

    ### ASCVD 10-Year Risk Classification

    • High Risk (≥ 20%)
    • Intermediate (7.5% to 19.9%)
    • Borderline (5% to 7.4%)
    • Low (< 5%)

    ### Causes of Hyperlipidemia

    • Drugs
      • Diuretics, cyclosporine, glucocorticoids, amiodarone, SGLT2 inhibitors
      • Oral estrogens, glucocorticoids, anabolic steroids, BAS, protease inhibitors, raloxifene, tamoxifen, beta blockers (not carvedilol), thiazides, antipsychotics
    • Diseases
      • Biliary obstruction, nephrotic syndrome, hypothyroidism, obesity, pregnancy
      • Nephrotic syndrome, chronic renal failure, diabetes (poorly controlled), hypothyroidism, obesity, pregnancy

    ### 2018 ACC/AHA Cholesterol Guidelines - Statin Recommendations

    • Adults ≤ 75 yo with clinical ASCVD
      • High Intensity Statin
    • Adults 20-75 yo, LDL ≥ 190 mg/dl
      • High Intensity Statin
    • Adults 40-75 yo, diabetes, LDL > 70 mg/dl
      • Moderate – High Intensity Statin
    • Adults 40-75 yo, LDL > 70 < 189 mg/dl, 10-yr ASCVD risk ≥5.0%
      • Moderate – High Intensity Statin

    ### Statin Intensity

    • High-Intensity Statin (LDL 50%)
      • Rosuvastatin 20-40 mg
      • Atorvastatin 40-80 mg
    • Moderate-Intensity Statin (LDL 30-50%)
      • Rosuvastatin 5-10 mg
      • Atorvastatin 10-20 mg
      • Simvastatin 20-40 mg
      • Pravastatin 40-80 mg
      • Lovastatin 40 mg
      • Fluvastatin XL 80 mg
      • Pitavastatin 2-4 mg
    • Low-Intensity Statin (LDL 30-50%)
      • Simvastatin 10 mg
      • Pravastatin 10-20 mg
      • Lovastatin 20 mg
      • Fluvastatin 20-40 mg
      • Pitavastatin 1 mg

    ### Statin Equivalency Chart

    • Medication - Equivalent Dose
    • Fluvastatin - 80 mg
    • Lovastatin - 40 mg
    • Pravastatin - 40 mg
    • Simvastatin - 20 mg
    • Atorvastatin - 10 mg
    • Rosuvastatin - 5 mg
    • Pitavastatin - 2 mg

    ### Statin LDL Reduction

    • Each 1% LDL reduction reduces the risk of ASCVD by 1%

    ### Statin Recommendations & Patient Profiles

    • Adults ≤ 75 yo with clinical ASCVD
      • High-intensity statin to reduce LDL ≥ 50%
    • High-intensity statin contraindicated or not tolerated
      • Moderate-intensity statin to reduce LDL 30-50%
    • Patients with ASCVD, maximum tolerated statins, AND LDL ≥ 70 mg/dl or non-HDL ≥ 100 mg/dl
      • Add ezetimibe
    • Patients with HFrEF, reasonable life expectancy (3- 5 years), not already on statin for ASCVD
      • Consider initiation of moderate-intensity statin to reduce ASCVD risk

    ### Statin Recommendations for Adults > 75 yo with Clinical ASCVD

    • Adults > 75 yo, with clinical ASCVD
      • Initiate moderate or high-intensity statin therapy
    • Adults > 75 yo, with clinical ASCVD, already tolerating high-intensity statin
      • Continue high-intensity statin

    ### Statin Recommendations for Very High-Risk ASCVD Patients

    • Multiple major ASCVD events OR One major ASCVD event WITH multiple high-risk condition
      • High-risk Conditions
        • ≥ 65 yo
        • HeFH
        • Hx of CABG or PCI outside of major ASCVD event
        • Ischemic CVA
        • Symptomatic PAD
        • DM
        • HTN
        • CKD (eGFR 15-59 ml/min)
        • Current smoking
        • LDL ≥ 100 mg/dl despite max tolerated statin + ezetimibe
        • CHF
      • Major ASCVD Events
        • Recent ACS (past 12 months)
        • Hx of MI
        • Ischemic CVA
        • Symptomatic PAD
          • Claudication w/ ABI < 0.85
          • Revascularization
          • Amputation

    #### Statin Recommendations and Patient Profiles

    • Adults ≤ 75 yo with very high-risk ASCVD, on maximum tolerated statin, LDL ≥ 70 mg/dl or non-HDL ≥ 100 mg/dl
      • Add ezetimibe
    • Patients with very high-risk ASCVD, on maximum tolerated LDL-lowering therapy (statin + ezetimibe) AND LDL ≥ 70 mg/dl or non-HDL ≥ 100 mg/dl
      • Add PCSK9 inhibitor following a clinician-patient discussion

    ### Clinical ASCVD Events

    • MI
    • CVA
    • PAD
    • Heart Failure
    • Hypertension

    ### LDL Goals for ASCVD

    • Patients with ASCVD
      • Goal LDL < 70 mg/dl

    ### LDL-Lowering Drug Options

    • Niacin
    • Fenofibrate
    • Ezetimibe
    • Evolocumab

    ### Statin Recommendations for Patients ≥ 20 yo with Hyperlipidemia

    • Adults 20-75 yo, LDL ≥ 190 mg/dl
      • High-intensity statin (maximum-intensity tolerated)
    • Adults 20-75 yo, LDL ≥ 190 mg/dl, less then 50% LDL reduction on max statins, AND/OR LDL > 100 mg/dl
      • Add ezetimibe
    • Adults 20-75 yo, LDL ≥ 190 mg/dl, less then 50% LDL reduction, on max tolerated statin and ezetimibe, AND TG ≤ 300 mg/dl
      • Add BAS
    • **Adults 30-75 yo, HeFH, LDL > 100 mg/dl, on max tolerated statin and ezetimibe **
      • Add PCSK9 inhibitor (PCSK9 mAB)
    • Adults 40-75 yo, baseline LDL ≥ 220 mg/dl, LDL ≥ 130 mg/dl, on max tolerated statin and ezetimibe
      • Add PCSK9 inhibitor (PCSK9 mAB)

    ### Statin Recommendations for Patients with Diabetes

    • Adults 40-75 yo, diabetes, regardless of 10-year ASCVD risk
      • Moderate-intensity statin
    • Adults with diabetes with multiple ASCVD risk factors, OR 10-year risk ≥ 20%
      • High-intensity statin
    • Adults with diabetes and 10-year risk ≥ 20%, on maximally tolerated statin dose
      • Add ezetimibe to lower LDL > 50% (No specific LDL target)
    • Adults 20-39 yo, and Diabetes-specific risk enhancers
      • Consider moderate-intensity statin

    ### Diabetes-Specific Risk Enhancers

    • Long duration of diabetes
      • T2DM ≥ 10 yrs
      • T1DM ≥ 20 yrs
    • Albuminuria (> 30 mcg)
    • eGFR < 60 ml/min
    • Retinopathy
    • Neuropathy
    • ABI 10%

    ### Key Points for Treating Patients with Diabetes and Hyperlipidemia

    • 40-75 yo, with diabetes, moderate intensity statin
    • 40-75 yo, with diabetes and higher CV risk (≥ 1 ASCVD risk factors), high-intensity statin
      • Target LDL < 70 mg/dl
    • 40-75 yo, with diabetes, multiple ASCVD risk factors, and LDL ≥ 70 mg/dl
      • Add ezetimibe or PCSK9 inhibitor to maximum tolerated statin
    • 20-39 yo, with diabetes, reasonable to start statin

    ### Statin Recommendations for Secondary Prevention

    • Secondary prevention:
      • High-intensity statin
      • Goal LDL ≤ 55 mg/dl
      • Add ezetimibe or PCSK9 inhibitor to maximum tolerated statin
    • If statin tolerant:
      • PCSK9 inhibitor
      • Bempedoic acid
      • Inclisiran
    • Elevated TG (135-499 mg/dl) despite statin therapy
      • Add Icosapent ethyl

    ### Risk Enhancing Factors

    • Family History (FmHx) of premature ASCVD (male < 55 yo, female < 65 yo)
    • LDL ≥ 160-189 mg/dl, non-HDL 190-220 mg/dl
    • Metabolic syndrome
    • CKD (not on dialysis)
    • Chronic inflammatory diseases (RA, psoriasis, HIV/AIDS)
    • Premature menopause (< 40 yo) or pre-eclampsia
    • South Asia race
    • Lipid biomarkers
      • TG ≥ 175 mg/dl, persistently elevated
      • ApoB ≥ 130 mg/dl (esp.w/ ↑ TG)
      • Lp(a) ≥ 50 mg/dl
      • hsCRP ≥ 2 mg/L
      • ABI < 0.9

    ### Statin Benefits Outweigh Risks

    • Benefits of statins in ASCVD reduction outweigh the risks
      • Do not stop the statin
    • Statins cause a small but clinically insignificant increase in A1C.
    • Statins cause asymptomatic transaminase (> 3X ULN) in 1% of patients
      • Dose related
      • Statins increase ALT > AST
    • Severe liver injury is very rare with statins (0.001%)
      • Routine monitoring is NOT recommended by the FDA
        • Baseline check, and then as “clinically warranted”.
        • Be alert to signs or symptoms of hepatotoxicity.
    • Rosuvastatin 40 mg → transient proteinuria, hematuria
    • Statins are not linked to AKI or worsening renal function, except with rhabdomyolysis

    ### Statin Drug Interactions

    • Inhibition of P-gp, CYP3A4, OATP1B1
    • Grapefruit juice inhibits 3A4
    • Gemfibrozil inhibits OATP1b1. Avoid with all statins.
    • OATP1B1/3 moves drug from portal circulation to hepatocyte.
    • P-gp moves drug from blood to intestine.

    Statin Dose Reduction

    • Reduce or avoid simvastatin or lovastatin doses when used alongside P-gp and 3A4 inhibitors, such as protease inhibitors, fungal azoles, cyclosporine, macrolides, amiodarone, amlodipine, and non-DHP CCBs (verapamil, diltiazem).

    Lifestyle Modifications

    • Dietary changes: Increase vegetables, fruits, legumes, nuts, whole grains, and fish. Favor mono- and polyunsaturated fats. Reduce cholesterol and sodium intake. Minimize consumption of processed meats, refined carbohydrates, and sweetened beverages. Avoid trans fats.

    Physical Activity Recommendations

    • The 2019 SCC/AHA Guideline on the Primary Prevention of Cardiovascular Disease recommends 150 minutes per week of moderate-intensity aerobic physical activity OR 75 minutes per week of vigorous-intensity aerobic physical activity.
    • Any amount of moderate or vigorous-intensity physical activity can be beneficial for cardiovascular health.

    Cardiovascular Health Goals

    • Aim for 150 minutes per week of moderate-intensity aerobic physical activity, or 75 minutes per week of vigorous-intensity aerobic physical activity.

    Ezetimibe

    • Inhibits cholesterol absorption at the brush border of the small intestine
    • Targets NPC1L1 receptor
    • Decreases delivery of cholesterol to the liver
    • Decreases hepatic cholesterol stores
    • Decreases LDL

    Ezetimibe Clinical Trial

    • Study design: randomized, double-blind
    • Patients: 18,144 with ACS within 10 days, LDL 50-100 mg/dl if on meds, 50-125 mg/dl if not on meds.
    • Randomized to simvastatin 40 mg + ezetimibe 10 mg daily or simvastatin 40 mg x 6 yrs
    • Primary outcome: composite of CV death, nonfatal MI, nonfatal CVA, UA w hospitalization, coronary revascularization
    • Results: simvastatin + ezetimibe had a statistically significant lower rate of primary outcomes compared to simvastatin alone (HR 0.936, p-value 0.016)
    • Ezetimibe added to statins reduces MACE (major adverse cardiovascular events)

    PCSK9 mAbs (Evolocumab, Alirocumab)

    • PCSK9 reduces LDL receptor numbers by blocking recycling
    • mAb binds to PCSK9
    • Inhibits PCSK9 from binding to LDL-receptors
    • Increases LDL-receptors by increasing receptor recycling
    • Increased LDL receptor numbers leads to decreased plasma LDL

    PCSK9 mAb Clinical Trial (Evolocumab)

    • Study design: randomized, double-blind, placebo-controlled, conducted in 1242 centers across 49 countries
    • Patients: 27,564 with established ASCVD and LDL ≥ 70 mg/dl on statins (69% on high-intensity)
    • Medications: Evolocumab 140 mg SC q 2 weeks or 420 mg SQ monthly OR placebo
    • Primary outcome: composite of CV death, MI, CVA, hospitalization for unstable angina, coronary revascularization
    • Follow-up: 2.2 years
    • Results: Evolocumab had significantly lower primary outcome rates compared to placebo (HR 0.85)

    Ezetimibe

    • Inhibits cholesterol absorption at the brush border of the small intestine
    • Targets NPC1L1 receptor
    • Decreases delivery of cholesterol to the liver
    • Decreases hepatic cholesterol stores
    • Decreases LDL
    • In a randomized, double-blind study of 18,144 patients with ACS within 10 days, LDL 50-100 mg/dl if on meds, 50-125 mg/dl if not on meds, simvastatin 40 mg + ezetimibe 10 mg daily had a lower incidence of CV death, nonfatal MI, nonfatal CVA, UA w hospitalization, coronary revascularization compared to simvastatin 40 mg x 6 years.

    PCSK9 mAbs (Evolocumab, Alirocumab)

    • PCSK9  LDL receptor numbers by blocking recycling
    • mAb binds to PCSK9
    • Inhibits PCSK9 from binding to LDL-receptors
    • Increases LDL-receptors by increasing receptor recycling
    • Increased LDL receptor numbers leads to decreased plasma LDL
    • In a randomized, double-blind, placebo controlled study of 27,564 patients WITH ASCVD, LDL ≥ 70 mg/dl on statins (69% on high-intensity), the group who received evolocumab 140 mg SubQ q 2 weeks or 420 mg SQ monthly had a lower incidence of CV death, MI, CVA, hospitalization for unstable angina, coronary revascularization compared to placebo.

    Hyperlipidemia

    • 86 million US adults ≥ 20 years old have TC > 200 mg/dl
    • 33-36% of US adults
    • 25 Million above 240 mg/dl
    • Hyperlipidemia, atherosclerosis and ASCVD are all related
    • Dyslipidemia/Hyperlipidemia:
      • ↑ LDL
      • ↑ VLDL (TG)
      • ↓ HDL
      • ↑ Age
    • Cigarette smoking
    • Hypertension
    • Diabetes

    Atherosclerotic Cardiovascular Disease (ASCVD) Risk Assessment

    • 10-year Risk of ASCVD:
      • Adults ≤ 75 years old with clinical ASCVD -> high intensity statins to reduce LDL ≥ 50%
      • Adults 20-75 years old with LDL ≥ 190 mg/dl -> high intensity statins
      • Adults 40-75 years old with diabetes and LDL > 70 mg/dl -> moderate - high intensity statins
      • Adults 40-75 years old with LDL > 70 < 189 mg/dl and a 10-year ASCVD risk ≥ 5.0% -> moderate - high intensity statins
    • Secondary causes of hyperlipidemia:
      • Adults ≤ 75 years old with clinical ASCVD
      • Adults 20-75 years old, LDL ≥ 190 mg/dl

    Statin Benefit Groups & Therapy Recommendations - 2018 ACC/AHA Cholesterol Guidelines

    • Statin Therapy:
      • Adults ≤ 75 years old with clinical ASCVD -> high-intensity statin. If contraindicated or not tolerated, then moderate-intensity statin
      • Patients with ASCVD, maximum tolerated statins, with LDL ≥ 70 mg/dl or Non-HDL ≥ 100 mg/dl -> add ezetimibe
      • Patients with HFrEF, reasonable life expectancy of 3-5 years, not already on statin for ASCVD -> consider moderate-intensity statin therapy
    • Statin Therapy in Adults > 75 years old
      • Adults >75 years old with clinical ASCVD-> initiate moderate or high-intensity statin therapy.
      • Adults > 75 years old with clinical ASCVD, already tolerating a high-intensity statin -> continue high-intensity statin therapy

    Very High-Risk ASCVD

    • Defined by:
      • Multiple major ASCVD events OR
      • One major ASCVD event WITH multiple high-risk conditions
    • Major ASCVD Events:
      • Recent ACS (past 12 months)
      • Hx of MI
      • Ischemic CVA
      • Symptomatic PAD (claudication w/ ABI < 0.85, revascularization, amputation)
    • High Risk conditions:
      • ≥ 65 yo
      • HeFH
      • Hx of CABG or PCI outside of major ASCVD event
      • DM
      • HTN
      • CKD (eGFR 15-59 ml/min)
      • Current smoking
      • LDL ≥ 100 mg/dl despite max tolerated statin + ezetimibe
      • CHF
    • Statin Therapy Recommendations:
      • Adults ≤ 75 yo with very high-risk ASCVD on maximum tolerated statin, LDL ≥ 70 mg/dl or Non-HDL ≥ 100 mg/dl-> add ezetimibe
      • Patients with very high-risk ASCVD on maximum tolerated LDL-lowering therapy (statin + ezetimibe), LDL ≥ 70 mg/dl or Non-HDL ≥ 100 mg/dl -> add PCSK9 inhibitor

    Statin Benefit Groups & Therapy Recommendations - 2018 ACC/AHA Cholesterol Guidelines - Cont.

    • High-intensity statin:
      • Rosuvastatin 20-40 mg
      • Atorvastatin 40-80 mg
    • Moderate-intensity statin:
      • Rosuvastatin 5-10 mg
      • Atorvastatin 10-20 mg
      • Simvastatin 20-40 mg
      • Pravastatin 40-80 mg
      • Lovastatin 40 mg
      • Fluvastatin XL 80 mg
      • Pitavastatin 2-4 mg
    • Low-intensity statin:
      • Simvastatin 10 mg
      • Pravastatin 10-20 mg
      • Lovastatin 20 mg
      • Fluvastatin 20-40 mg
      • Pitavastatin 1 mg
    • Each 1% LDL reduction reduces risk of ASCVD by 1%

    Statin Intolerance

    • Statin Intolerance is defined by:
      • Muscle symptom(s) of myalgia, myopathy or rhabdomyolysis that occur with statin use, and are of sufficient severity to warrant discontinuation of statin therapy

    Statin-Associated Adverse Drug Reactions

    • Asymptomatic transaminase (> 3X ULN) in 1% of patients
      • Dose related
      • Statins increase ALT > AST
    • Severe liver injury is very rare (<0.001%)
    • Routine monitoring for liver function NOT recommended by the FDA
      • Baseline, then as “clinically warranted”
      • Remain alert to signs or symptoms hepatotoxicity
    • Rosuvastatin 40 mg -> transient proteinuria, hematuria
    • Statins are not linked to AKI or worsening of renal function, except with rhabdomyolysis

    Statin Drug Interactions

    • Inhibition of P-gp, CYP3A4, OATP1B1
    • Grapefruit juice inhibits 3A4
    • Gemfibrozil inhibits OATP1b1. Avoid with all statins.
    • Avoid or reduce simvastatin or lovastatin dose with P-gp and 3A4 inhibitors:
      • protease inhibitors
      • fungal azoles
      • cyclosporine
      • macrolides
      • amiodarone
      • amlodipine
      • Non-DHP CCBs (verapamil, diltiazem)

    Lifestyle Modifications for Patients with Hyperlipidemia

    • Diet
    • Physical activity
    • Weight reduction
    • Smoking cessation

    LDL Treatment Targets 2018 ACC/AHA Cholesterol Guidelines - Cont.

    • Adults 20-75 yo with LDL ≥ 190 mg/dl -> high-intensity statin (maximum-intensity tolerated)
    • Adults 20-75 yo with LDL ≥ 190 mg/dl and less then 50% LDL reduction on max statins, AND/OR LDL > 100 mg/dl -> add ezetimibe
    • Adults 20-75 yo with LDL ≥ 190 mg/dl, less then 50% LDL reduction on max tolerated statin and ezetimibe AND TG ≤ 300 mg/dl -> add BAS
    • Adults 30-75 yo, with HeFH and LDL > 100 mg/dl on max tolerated statin and ezetimibe -> add PCSK9 inhibitor (PCSK9 mAB)
    • Adults 40-75 yo with baseline LDL ≥ 220 mg/dl, LDL ≥ 130 mg/dl on max tolerated statin and ezetimibe -> add PCSK9 inhibitor (PCSK9 mAB)

    Diabetes & Statins

    • Adults 40-75 yo with diabetes, regardless of 10-year ASCVD risk -> moderate-intensity statin
    • Adults with diabetes with multiple ASCVD risk factors, OR 10-year risk ≥ 20% -> high-intensity statin
    • Adults with diabetes and 10-year risk ≥ 20% on maximally tolerated statin dose -> add ezetimibe to lower LDL > 50%
    • Adults 20-39 yo with diabetes and diabetes-specific risk enhancers -> consider moderate-intensity statin
    • 2019 AHA states that the benefits of statins in ASCVD reduction outweigh the risk. Do not stop the statins. Statins cause small but clinically insignificant ↑ A1c.

    Diabetes-Specific Risk Enhancers

    • Long duration of diabetes:
    • T2DM ≥ 10 yrs
    • T1DM ≥ 20 yrs
    • Albuminuria (> 30 mcg)
    • eGFR < 60 ml/min
    • Retinopathy
    • Neuropathy
    • ABI 10%
    • Lp(a) ≥ 50 mg/dl
    • hsCRP ≥ 2 mg/L
    • ABI < 0.9
    • A1C > 7.5
    • Metabolic Syndrome:
      • FBG > 100, A1C ≥ 6%, metabolic syndrome

    Moderate Vs. High Intensity Statins - ASCVD Risk

    • Adults 40-75 yo, with LDL > 70 < 189 mg/dl at high risk (≥ 20%) -> high-intensity statin
    • Adults 40-75 yo, with LDL > 70 < 189 mg/dl at intermediate risk (≥7.5% -> moderate-intensity statin

    Friedewald Equation & Non-HDL

    • Friedewald Equation is used to calculate LDL
    • Non-HDL:
      • Total cholesterol - HDL
      • Together considered very atherogenic

    Pharmacokinetic Properties of Statins

    • Absorption:
      • Well absorbed
      • Meal intake affects absorption
    • Distribution:
      • Wide tissue distribution
      • Crosses the blood-brain barrier
    • Metabolism:
      • Primarily metabolized in the liver
    • Elimination:
      • Excreted in bile

    Apolipoprotein B (ApoB)

    • Primary protein embedded in LDL and VLDL
    • Strong predictor of atherogenicity

    Lipoproteins

    • LDL (low-density lipoprotein):
      • Primary carrier of cholesterol
      • Together considered Non-HDL
    • VLDL (very low-density lipoprotein):
      • Primary carrier of TG
      • Very atherogenic
    • HDL (high density lipoprotein):
      • not atherogenic
      • Also known as the “good” cholesterol

    Cholesterol & Triglycerides

    • Cholesterol
      • Sources: liver and diet
      • Functions:
        • Essential component of cell membranes
        • Precursor for steroid hormones
        • Essential for bile production
    • Triglycerides
      • Sources: liver and diet
      • Function: energy
      • Composed of glycerol and fatty acids
      • Most common type of fat in the body

    Hyperlipidemia Management Guidelines

    • ASCVD Risk Factors:

      • High Risk: ASCVD events, multiple risk factors, or a 10-year risk ≥ 20%
      • Intermediate Risk: 10-year risk ≥ 7.5% and < 20%
      • Borderline Risk: 10-year risk < 7.5%
      • Diabetes-specific risk factors: Diabetes with a 10-year risk ≥ 7.5%

    • Lipid Targets:

      • LDL: < 70 mg/dL for high-risk individuals, < 100 mg/dL for intermediate risk
      • Non-HDL: < 100 mg/dL for high-risk individuals, < 130 mg/dL for intermediate risk

    • Statin Intensity:

      • High Intensity: Recommended for high-risk patients
      • Moderate Intensity: Recommended for intermediate risk

    • Second-line Therapy:

      • Ezetimibe: A common second-line treatment
      • PCSK9 mAb: A monoclonal antibody that can lower LDL cholesterol

    • Third-line Therapy:

      • PCSK9 mAb: Added or replaced in some instances
      • Bempedoic acid or Inclisiran: Alternative third-line treatments
      • Evinacumab: Used for patients with familial hypercholesterolemia

    • Fourth-line Therapy:

      • Bempedoic acid or Inclisiran: Used as fourth-line, if needed

    • Persistent Hypertriglyceridemia:

      • Icosapent ethyl: Recommended for patients ≥ 50 years old with at least one ASCVD risk factor

    Key Points

    • The management of hyperlipidemia is tailored to the individual patient's risk level.
    • High-intensity statins are the first-line treatment for high-risk individuals.
    • Several second and third-line options exist, including ezetimibe, PCSK9 monoclonal antibodies, and other newer medications.
    • For patients with persistent hypertriglyceridemia, icosapent ethyl can be considered.

    Red Yeast Rice

    • Contains monacolin K, a statin that lowers cholesterol.
    • May have similar effects to prescription statin drugs.

    Garlic

    • May lower cholesterol, but further research is needed.
    • Studies have shown mixed results on garlic's effects on cholesterol levels.
    • One meta-analysis suggests garlic can reduce LDL cholesterol and triglyceride levels.
    • May have anti-inflammatory properties, potentially beneficial for cardiovascular health.
    • May interact with certain medications, so talk to your doctor before using garlic supplements.

    Statin Therapy

    • Mechanism of Action: Statin therapy primarily inhibits the enzyme HMG-CoA reductase, responsible for cholesterol synthesis in the liver.
    • Common Side Effects: Statin therapy is generally well-tolerated. Common side effects include muscle aches (myalgia), elevated liver enzymes, and gastrointestinal upset.
    • Not a Common Side Effect: Diabetes is not a common side effect of statin therapy.
    • Liver Enzyme Monitoring: Routine monitoring of liver enzymes is recommended by the FDA for statin users.

    PCSK9 Inhibitors

    • Primary Indication: PCSK9 inhibitors are primarily indicated for patients with hypercholesterolemia (high cholesterol) who are unable to achieve their LDL cholesterol goals with statin therapy alone.
    • Mechanism of Action: PCSK9 inhibitors increase LDL receptor levels in the body.

    Lifestyle Modifications

    • Dietary Recommendations: Individuals aiming for cardiovascular health should include fruits, vegetables, whole grains, and lean proteins in their diet.
    • Physical Activity: Moderate-intensity aerobic physical activity is recommended for at least 150 minutes per week. Vigorous-intensity exercise is recommended for 75 minutes per week.

    Niacin Therapy

    • Common Side Effect: Flushing is a common side effect associated with niacin therapy.

    Fibrate Therapy

    • Lipid Impact: Fibrates primarily impact triglycerides (TG), reducing levels and increasing HDL cholesterol.

    Other Therapies

    • Grapefruit Juice: Grapefruit juice inhibits the enzyme CYP3A4, affecting statin metabolism.
    • Statin Effect on A1c: Statins cause a small but clinically insignificant increase in A1c levels.

    Friedewald Equation

    • Purpose: The Friedewald Equation is a mathematical formula used to calculate LDL cholesterol.
    • Normal Range: The normal range for LDL cholesterol is below 100 mg/dL.

    Cardiovascular Disease (CVD)

    • Key Risk Factor: High blood pressure (hypertension) is a key risk factor for CVD.

    High-Intensity Statin Therapy

    • Definition: High-intensity statin therapy refers to statin doses known to reduce LDL cholesterol by at least 50%.
    • Example: Atorvastatin 80mg is considered a high-intensity statin therapy.

    Low-Intensity Statin Therapy

    • Example: Pravastatin 40mg is considered a low-intensity statin therapy.

    Triglycerides

    • High Levels: High levels of triglycerides are considered a significant risk factor for cardiovascular disease.

    Diabetes and ASCVD

    • Risk Factor: 10 years of diabetes is considered a risk factor for atherosclerotic cardiovascular disease (ASCVD).

    Drug Therapy Match

    • Statins: Reduce LDL cholesterol levels
    • Fibrates: Primarily target triglycerides
    • PCSK9 Inhibitor: Increases LDL receptor levels

    Non-HDL Cholesterol

    • Equation: Non-HDL cholesterol = Total Cholesterol - HDL Cholesterol

    Physical Activity for CVD Prevention

    • Recommendation: The recommended physical activity goal for CVD prevention is at least 150 minutes per week of moderate-intensity aerobic physical activity or 75 minutes per week of vigorous-intensity aerobic physical activity.

    ASCVD Risk

    • High-Risk Percentage: A 10-year ASCVD risk of ≥ 20% classifies adults as high risk.

    HDL Levels and ABI

    • Significance of HDL: High levels of HDL cholesterol are beneficial for heart health, considered "good" cholesterol.
    • ABI < 0.9: An ankle-brachial index (ABI) less than 0.9 indicates peripheral artery disease, a condition that increases CVD risk.

    Statins and Avoidance

    • Avoidance: All statins should be avoided in conjunction with grapefruit juice due to potential drug interactions.

    LDL Calculation

    • Friedewald Equation: LDL Cholesterol = Total Cholesterol - HDL Cholesterol - (Triglycerides/5)

    10-Year ASCVD Risk Factors

    • Factors: Age, gender, race, family history, smoking status, blood pressure, diabetes, high cholesterol, and other relevant factors.

    Statin Benefit Groups

    • 2018 ACC/AHA Guidelines: The 2018 ACC/AHA Cholesterol Guidelines define four statin benefit groups:
      • Patients with clinical ASCVD
      • Patients with LDL ≥190 mg/dL
      • Patients with diabetes aged 40-75 years with LDL ≥ 70 mg/dL
      • Patients with a 10-year ASCVD risk ≥ 7.5%

    Statin Intensity

    • Low-Intensity Statins: Pravastatin, Simvastatin (10mg), Fluvastatin
    • Moderate-Intensity Statins: Simvastatin (20mg), Lovastatin, Rosuvastatin (5-10mg)
    • High-Intensity Statins: Atorvastatin (40-80mg), Rosuvastatin (20-40mg)

    Statin Intolerance

    • Definition: Statin intolerance is characterized by muscle symptoms (myalgia, myopathy, rhabdomyolysis) experienced by a patient while taking a statin.

    Triglycerides Function

    • Primary Function: The primary function of triglycerides is to store energy and are transported through the bloodstream by very-low-density lipoprotein (VLDL) particles.

    Friedewald Equation

    • Equation: LDL Cholesterol = Total Cholesterol - HDL Cholesterol - (Triglycerides/5)

    Desirable LDL Level

    • Level: A desirable LDL cholesterol level is below 100mg/dL.

    CVD Risk Factors

    • Conditions:
      • High blood pressure
      • Smoking
      • Diabetes
      • Family history of CVD
      • Obesity
      • High cholesterol
      • Low HDL cholesterol
      • Age
      • Ethnicity
      • Genetic Predisposition
      • Certain inflammatory conditions

    Hyperlipidemia Lifestyle Modifications

    • Recommendations:
      • Healthy diet: Choose low-fat, low-cholesterol foods, fruits, vegetables, and whole grains.
      • Regular physical activity: Aim for at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic activity per week.
      • Weight management: Weight loss can significantly improve lipid levels.
      • Smoking cessation: Quitting smoking is crucial.

    Statin Therapy for LDL ≥ 190 mg/dL

    • Recommendation: Adults between 20-75 years old with an LDL ≥ 190 mg/dL should initiate statin therapy regardless of their 10-year ASCVD risk.

    Ezetimibe Mechanism of Action

    • Mechanism: Ezetimibe blocks the absorption of cholesterol in the small intestine.

    Non-Statin Therapies Impact

    • LDL: Non-statin therapies can further lower LDL levels beyond what can be achieved with statins alone.
    • HDL: Some non-statin therapies can also increase HDL levels, which is beneficial for heart health.
    • TG: Non-statin therapies can reduce triglycerides, especially in patients with hypertriglyceridemia.

    Non-Statin Therapy and ASCVD Outcomes

    • Outcomes: Some studies have shown that non-statin therapies can further reduce the risk of ASCVD events when added to statin therapy.

    Non-Statin Therapy Order of Use

    • Statin Benefit Groups:
      • Group 1 (Clinical ASCVD): Consider adding ezetimibe or PCSK9 inhibitors if LDL ≥ 70 mg/dL despite maximum tolerated statin therapy.
      • Group 2 (LDL ≥ 190 mg/dL): Consider ezetimibe or PCSK9 inhibitors as initial therapy or in combination with statins.
      • Group 3 (Diabetes, 40-75 years, LDL ≥ 70 mg/dL): The addition of non-statin therapies is not recommended unless the 10-year ASCVD risk is high (≥ 7.5%).
      • Group 4 (10-year ASCVD risk ≥ 7.5%): Consider non-statin therapies if the 10-year risk is high and LDL remains elevated despite statin therapy.

    Persistent Hypertriglyceridemia Definition

    • Components:
      • Triglyceride levels ≥ 500 mg/dL (≥ 5.6 mmol/L) despite lifestyle modifications.
      • No secondary causes contributing to hypertriglyceridemia.

    Secondary Causes of Hypertriglyceridemia

    • Common Causes:
      • Diabetes
      • Hypothyroidism
      • Alcohol abuse
      • Kidney disease
      • Certain medications

    Icosapent Ethyl Benefits

    • Patient Populations:
      • High-risk patients with elevated triglycerides
      • Patients with high-risk ASCVD and persistent hypertriglyceridemia

    Ezetimibe and Simvastatin Combination

    • Outcome: Adding ezetimibe to simvastatin leads to a further reduction in LDL cholesterol.

    PCSK9 Inhibitors Mechanism of Action

    • Mechanism: PCSK9 inhibitors bind to and inhibit the PCSK9 protein, preventing it from degrading LDL receptors, leading to increased LDL uptake from the blood.

    PCSK9 Inhibitors Primary Outcome

    • Outcome: The primary outcome measured in studies involving PCSK9 inhibitors is the reduction of cardiovascular events, including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death.

    Bempedoic Acid Mechanism of Action

    • Mechanism: Bempedoic acid inhibits the enzyme ATP citrate lyase, reducing cholesterol synthesis in the liver.

    NPC1L1 Receptor Therapy

    • Targeted Therapy: Ezetimibe primarily targets the NPC1L1 receptor, blocking cholesterol absorption.

    Non-Statin Therapies and HDL Levels

    • Impact: Some non-statin therapies, particularly fibrates, can increase HDL levels, which is beneficial for cardiovascular health.

    Persistent Hypertriglyceridemia Key Component

    • Component: Persistent hypertriglyceridemia involves having triglyceride levels ≥ 500mg/dL (≥ 5.6 mmol/L) despite lifestyle modifications.

    Incilisiran Therapy Beneficiaries

    • Patient Population: Patients with familial hypercholesterolemia who are unable to achieve their LDL cholesterol targets with statins are likely to benefit from incilisiran therapy.

    Secondary Causes of Hypertriglyceridemia

    • Common Cause: Alcohol abuse is a secondary cause of hypertriglyceridemia.

    Cholesterol Absorption Inhibition

    • Therapy: Ezetimibe is known to inhibit cholesterol absorption, reducing LDL cholesterol levels.

    Icosapent Ethyl Classification

    • Classification: Icosapent ethyl is classified as a omega-3 fatty acid therapy.

    Non-Statin Therapy Usage Order

    • Recommended Order:
      • Ezetimibe: Often the first-line non-statin therapy to add.
      • PCSK9 inhibitors: Considered for patients who are unable to achieve their LDL targets with statins and ezetimibe.
      • Bempedoic acid: Often the third-line addition if other non-statin therapies are not effective.
      • Icosapent ethyl: Used for patients with high triglycerides.

    Non-Statin Therapies and Triglyceride Levels

    • Impact: Non-statin therapies can often significantly reduce triglyceride levels, especially in patients with hypertriglyceridemia.

    Simvastatin and Ezetimibe Study

    • Primary Outcome: The primary outcome defined in the study involving Simvastatin and Ezetimibe was the reduction in the combined endpoint of coronary heart disease (CHD) death, nonfatal MI, and nonfatal stroke.

    Combined Therapy Effect

    • Primary Outcome Percentage: The addition of Ezetimibe to Simvastatin resulted in a 21% reduction in the risk of cardiovascular events compared to Simvastatin alone.

    Simvastatin Alone Nonfatal MI

    • Percentage: Patients taking Simvastatin alone had a 5.0% rate of nonfatal Myocardial Infarction (MI).

    Evolocumab Impact

    • Primary Endpoint: Evolocumab significantly reduced the primary endpoint of cardiovascular events compared to placebo.

    Nonfatal MI Hazard Ratio

    • Hazard Ratio (HR): The hazard ratio (HR) for nonfatal MI comparing Simvastatin plus Ezetimibe to Simvastatin alone was 0.81.

    PCSK9 Inhibitors and LDL Receptor Recycling

    • Effect: PCSK9 inhibitors inhibit the recycling of LDL receptors, leading to increased LDL clearance from the blood.

    Simvastatin and Ezetimibe Ischemic CVA

    • Rate: The combination therapy of Simvastatin plus Ezetimibe resulted in a 36% reduction in ischemic CVA rates compared to Simvastatin alone.

    Evolocumab Study Follow-up

    • Duration: The Evolocumab study had a follow-up duration of 2.7 years.

    Evolocumab and MACE Risk

    • MACE Risk: The risk of major adverse cardiovascular events (MACE) was significantly lower in patients taking Evolocumab compared to those taking a placebo.

    Subcutaneous LDL Management

    • Medication: Evolocumab is administered as a subcutaneous injection for managing LDL levels.

    ASCVD Risk Classification

    • Classification: A patient aged 46 with a 10-year ASCVD risk of 15% due to diabetes should be classified as moderate risk.

    High-Intensity Statin Therapy Indication

    • Indication: A patient with clinically documented ASCVD, regardless of their 10-year risk assessment, is indicated for high-intensity statin therapy.

    Secondary Cause of Hyperlipidemia

    • Secondary Cause: Hypothyroidism can be a secondary cause of hyperlipidemia.

    Statin Therapy for Diabetic Adults

    • LDL Level Requirement: For an adult aged 40-75 with diabetes, statins are recommended if their LDL cholesterol is ≥ 70 mg/dL.

    LDL Reduction and ASCVD Risk

    • Risk Reduction: Each 1% reduction in LDL cholesterol reduces the risk of ASCVD by approximately 1%.

    Atorvastatin High-Intensity Dose Range

    • Dose Range: The high-intensity statin therapy dose range for Atorvastatin is 40-80 mg daily.

    Statin Side Effect

    • Not Common: Vision changes are not commonly associated with statin therapy.

    Statin Therapy for High-Risk Patient

    • Recommendation: For an individual aged 46 with an LDL of 170 mg/dL and a 10-year ASCVD risk of 15%, moderate-intensity statin therapy is recommended.

    Statin Dose Equivalence

    • Pravastatin Equivalent: The equivalent dose of Pravastatin that corresponds to Simvastatin 20 mg is 40 mg.

    10-Year ASCVD Risk Factors

    • Not Considered: Height is not considered when determining the 10-year ASCVD risk.

    ASCVD Statin Therapy

    • Recommendation: For adults ≤ 75 years old with clinical ASCVD, high-intensity statin therapy is recommended.

    LDL ≥ 70 mg/dL with Maximum Tolerated Statins

    • Recommendation: For patients with ASCVD who are on the maximum tolerated statins but have LDL levels ≥ 70 mg/dL, consider adding ezetimibe or PCSK9 inhibitors.

    Moderate-Intensity Statin for HFrEF

    • Scenario: A moderate-intensity statin should be considered for patients with heart failure with reduced ejection fraction (HFrEF) if they have a history of ASCVD.

    High-Intensity Statin for Adults Over 75

    • Recommendation: For adults over 75 years old with clinical ASCVD who are already tolerating high-intensity statin therapy, continue with the same therapy.

    High-Risk ASCVD Therapy Addition

    • Addition: For adults ≤ 75 years old with very high-risk ASCVD on maximum tolerated statin therapy with LDL ≥ 70 mg/dL, consider adding ezetimibe or PCSK9 inhibitors.

    Very High-Risk ASCVD Therapy

    • Therapy: For patients with very high-risk ASCVD who are on maximum tolerated LDL-lowering therapy, consider adding PCSK9 inhibitors or icosapent ethyl if the patient has persistent hypertriglyceridemia.

    Very High-Risk ASCVD Factors

    • Factors:
      • Clinical ASCVD with diabetes
      • Previous cardiovascular event
      • Multiple risk factors
      • High-risk genetic predisposition

    High-Risk Condition for ASCVD

    • Condition: Diabetes with multiple other ASCVD risk factors is considered a high-risk condition contributing to ASCVD risk classification.

    LDL Target for Very High-Risk ASCVD

    • Target: The LDL cholesterol target for patients with very high-risk ASCVD to consider additional therapy is < 55 mg/dL.

    Recommendation for Multiple ASCVD Events

    • Recommendation: For patients who have experienced multiple major ASCVD events, consider adding additional therapies to achieve the lowest LDL target possible.

    LDL Function

    • Function: LDL cholesterol transports cholesterol from the liver to the cells, but high levels can lead to plaque buildup in arteries (atherosclerosis).

    Significant Risk Factor for ASCVD

    • Risk Factor: Diabetes is considered a significant risk factor for developing ASCVD.

    Statin Benefit Groups in the 2018 Guidelines

    • Not a Group: The 2018 ACC/AHA guidelines do not include individuals with elevated total cholesterol as a separate statin benefit group.

    Apolipoprotein B (ApoB) Levels

    • Significance: An increased level of Apolipoprotein B (ApoB) indicates a higher risk of ASCVD.

    Triglyceride Carrying Lipoprotein

    • Lipoprotein: Very-Low-Density Lipoprotein (VLDL) is primarily responsible for carrying triglycerides.

    Hyperlipidemia Lifestyle Modification

    • Recommendation: Individuals with hyperlipidemia are recommended to make lifestyle changes such as:
      • Dietary modifications: Reducing saturated and trans fats, increasing fiber intake, and consuming a balanced diet.
      • Regular physical activity: Aim for at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic activity per week.
      • Weight management: Achieving and maintaining a healthy body weight can significantly improve lipid levels.
      • Smoking cessation: Quitting smoking is crucial for improving cardiovascular health.

    Statin Intolerance

    • Definition: Statin intolerance is characterized by muscle-related side effects, including myalgia (muscle aches), myopathy (muscle weakness), and in severe cases, rhabdomyolysis (muscle breakdown).

    Non-HDL Cholesterol Calculation

    • Method: Non-HDL cholesterol is calculated using the following equation: Non-HDL Cholesterol = Total Cholesterol – HDL Cholesterol.

    Statin Side Effect Incidence

    • Side Effect: While muscle side effects are the most common, a very low incidence of serious adverse events (serious allergic reactions, liver problems, or rhabdomyolysis) can occur with statin therapy.

    Hyperlipidemia Non-Statin Therapies

    • Ezetimibe

      • Mechanism: Blocks cholesterol absorption in the small intestine
      • Side Effects: Generally well-tolerated, minor GI discomfort and muscle pain are possible.
      • Clinical Efficacy: Adds to LDL reduction when combined with statins, can reduce cardiovascular events

    • PCSK9 Inhibitors (e.g., Alirocumab, Evolocumab)

      • Mechanism: Bind to PCSK9, preventing LDL receptor degradation, leading to increased LDL clearance
      • Side Effects: Injection site reactions, flu-like symptoms, overall low incidence
      • Clinical Efficacy: More effective than statins in certain high-risk individuals, significant LDL reductions, potential long-term cardiovascular benefits

    • Fibrates (e.g., Fenofibrate, Gemfibrozil)

      • Mechanism: Activate PPAR receptors, boosting lipoprotein lipase activity, leading to triglyceride breakdown
      • Side Effects: Gastrointestinal issues, myopathy (muscle weakness), liver problems
      • Clinical Efficacy: Mixed results on cardiovascular event reduction, primarily effective at lowering triglycerides, less impact on LDL

    • Niacin (Nicotinic Acid)

      • Mechanism: Reduces VLDL and LDL synthesis in the liver, elevates HDL levels by decreasing clearance
      • Side Effects: Flushing, itching, GI upset, liver toxicity at high doses
      • Clinical Efficacy: Uncertain benefit, use often limited due to side effects

    • Bile Acid Sequestrants (e.g., Cholestyramine, Colesevelam)

      • Mechanism: Bind bile acids in the intestines, decreasing reabsorption, leading to cholesterol usage for bile synthesis
      • Side Effects: GI discomfort, constipation, risk of nutrient malabsorption
      • Clinical Efficacy: Not covered in text.

    Clinical Recommendations

    • Non-statin therapies are used for patients who can't tolerate statins or have high cardiovascular risk despite statin treatment
    • Individualized treatment: Consider patient risk factors, LDL goals, and side effect profiles

    Bile Acid Sequestrants Mechanism

    • Bile acid sequestrants (BAS) bind bile acids in the gut, preventing their reabsorption.
    • This increases bile acid excretion, prompting the liver to convert more cholesterol into bile acids.
    • This leads to a decrease in circulating low-density lipoprotein (LDL) cholesterol.

    Comparing Therapy Effectiveness

    • BAS can reduce LDL cholesterol by 15-30%.
    • They are generally less effective than statins in lowering LDL cholesterol.
    • BAS can be used in patients who are statin-intolerant or in combination with statins.
    • PCSK9 inhibitors and ezetimibe are more effective than BAS in lowering LDL cholesterol.

    Side Effects of Bile Acid Sequestrants

    • Common side effects include gastrointestinal issues like constipation, bloating, flatulence, and abdominal pain.
    • Less common but notable side effects include malabsorption of fat-soluble vitamins (A, D, E, K) and increased triglyceride levels.
    • BAS are generally well tolerated but gastrointestinal discomfort can lead to patient non-compliance.

    Long-term Outcomes Of Treatment

    • Long-term use of BAS may modestly reduce the risk of cardiovascular events.
    • However, their role in reducing mortality is less clear compared to statins.
    • Monitoring lipid levels and liver function is recommended during long-term therapy.

    Patient Selection Criteria

    • Ideal candidates for BAS therapy include patients with primary hyperlipidemia and high LDL cholesterol levels.
    • They are suitable for individuals who are statin-intolerant or have a limited response to statins.
    • Patients with a history of cardiovascular events who require additional LDL-lowering therapies are also good candidates.
    • BAS therapy is best for patients who are willing to comply with dietary changes and medication regimens.
    • Potential drug interactions need to be considered, as BAS can affect the absorption of other medications.

    Bempedoic Acid

    • Inhibits ATP-citrate lyase, reducing cholesterol synthesis
    • Increases LDL receptor expression
    • Lowers LDL cholesterol and total cholesterol levels
    • Converted to its active form in the liver, minimizing systemic exposure

    Non-statin Therapies

    • Common Side Effects: Gastrointestinal issues (nausea, diarrhea) and muscle-related symptoms
    • Serious Effects: Increased risk of gout, possible liver enzyme elevation, and risk of cardiovascular events in specific populations

    Bempedoic Acid Clinical Efficacy

    • Reduces LDL cholesterol by 15-20%, both as monotherapy and in combination with statins
    • Ongoing studies evaluating long-term effects on cardiovascular events show positive trends in risk reduction
    • Effective when combined with other lipid-lowering agents, achieving better lipid control

    Lipid-lowering Agent Comparison

    • Statins: First-line therapy with proven efficacy in reducing cardiovascular events
    • Bempedoic Acid vs Statins: Comparable LDL reduction but with a different side-effect profile
    • PCSK9 Inhibitors: More potent LDL lowering, but have higher cost and subcutaneous administration
    • Fibrates: Effective for triglyceride reduction but limited LDL efficacy, risk of myopathy
    • Niacin: Not commonly used due to side effects, but effective in raising HDL

    Hyperlipidemia Management Guidelines

    • Risk Assessment: Use ASCVD risk calculators to determine treatment necessity
    • Lifestyle Modifications: Diet, exercise, and weight management are foundational
    • First-line Therapy: Statins are the primary option for high-risk individuals
    • Non-statin Therapy: Bempedoic acid and other non-statin options can be considered for patients who don't reach targets with statins or cannot tolerate them
    • Monitoring: Regular lipid panel evaluations and follow-up for side effects are crucial, especially when initiating or changing therapies

    Inclisiran Mechanism of Action

    • Inclisiran is a small interfering RNA (siRNA) therapy that targets PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9), a protein that regulates LDL cholesterol levels.
    • By inhibiting PCSK9, inclisiran reduces LDL receptor degradation in the liver, leading to increased LDL cholesterol clearance from the bloodstream.
    • Administered via subcutaneous injection, with dosing every six months after an initial loading dose.

    Clinical Efficacy of Inclisiran

    • Significantly reduces LDL cholesterol levels, typically achieving reductions of 50% or more from baseline.
    • Demonstrated efficacy in patients with atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia.
    • Clinical trials have shown inclisiran's effectiveness in lowering LDL cholesterol beyond that achieved by statins alone.
    • The duration of effect allows for reduced frequency of administration compared to other lipid-lowering therapies.

    Comparative Analysis with Statins

    • Statins primarily work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver.
    • Both therapies lower LDL cholesterol but have different mechanisms and patient responses.
    • Inclisiran may be beneficial for patients who are statin-intolerant or those who require additional LDL reduction despite maximum statin therapy.
    • Inclisiran has a favorable safety profile and lacks the common statin-related muscle side effects.

    Side Effects of Inclisiran

    • Generally well tolerated with a favorable safety profile.
    • Most common side effects include injection site reactions (pain, redness, swelling).
    • Mild and transient elevations in liver enzymes noted in some cases, requiring monitoring.
    • No significant risk of myopathy or rhabdomyolysis as seen with statins.
    • Potential allergic reactions or hypersensitivity are rare.

    Patient Selection for Inclisiran Therapy

    • Ideal for patients with hyperlipidemia who are at high cardiovascular risk.
    • Suitable for individuals with statin intolerance or those who do not achieve adequate LDL reduction with statins.
    • Consideration for patients with familial hypercholesterolemia.
    • Regular monitoring of LDL levels and liver function before and during treatment is recommended.
    • Consultations should assess potential drug interactions and contraindications related to individual health profiles.

    ANGPTL3 Inhibitors

    • ANGPTL3 is a protein involved in lipid metabolism, specifically, it inhibits lipoprotein lipase (LPL), preventing the breakdown of triglycerides.
    • Inhibiting ANGPTL3 leads to lower triglyceride levels and improved lipid profiles.
    • Evinacumab and Aro-APOC3 are monoclonal antibodies targeting ANGPTL3, meaning they bind to the protein and block its function.
    • Clinical trials, such as Evince (for Evinacumab) and APOLLO (for Aro-APOC3) have shown these drugs decrease triglycerides and LDL cholesterol levels significantly.
    • ANGPTL3 inhibitors can be considered adjunct therapies for patients unable to tolerate or benefit from statins.

    Mechanisms of Action

    • ANGPTL3 inhibitors work by inhibiting the action of lipoprotein lipase (LPL), which prevents the breakdown of triglycerides in the bloodstream.
    • By blocking LPL, these drugs decrease levels of triglyceride-rich lipoproteins and improve LDL cholesterol clearance.
    • ANGPTL3 inhibitors may also influence HDL metabolism, potentially enhancing reverse cholesterol transport, the process that removes cholesterol from the body.

    Comparative Effectiveness

    • ANGPTL3 inhibitors might be more effective in lowering lipids than traditional therapies.
    • They may be particularly beneficial for treating specific populations with genetic hyperlipidemias, where traditional drugs often fall short.
    • More research is needed to compare long-term outcomes and cardiovascular benefits of ANGPTL3 inhibitors compared to other non-statin therapies, such as PCSK9 inhibitors and fibrates.

    Side Effects Management

    • ANGPTL3 inhibitors generally have a good safety profile.
    • Common side effects include injection-site reactions, flu-like symptoms, and gastrointestinal disturbances.
    • Monitoring for allergic reactions and liver function tests is recommended during treatment initiation.
    • Patient education is important for managing and reporting side effects to ensure medication adherence and safety.

    Recommendation Levels

    • Class I: Procedure or treatment is beneficial and effective.
    • Class IIa: Procedure or treatment is reasonable to perform, with conflicting evidence or differing opinions on its effectiveness.
    • Class IIb: Procedure or treatment has less well-established effectiveness, with conflicting evidence or differing opinions.
    • Class III: Procedure or treatment is not beneficial, may be harmful, and is generally not recommended.

    Statin Therapy Initiation

    • Primary Prevention:
      • Statins are recommended for adults aged 40–75 with an LDL-C of 70-189 mg/dL and a 10-year ASCVD risk of 20% or higher.
      • Moderate intensity statin therapy should be considered for adults aged 40–75 with an LDL-C of 70-189 mg/dL and a 10-year ASCVD risk of 5% to less than 20%.
    • Secondary Prevention:
      • High-intensity statins are recommended for individuals with a history of cardiovascular disease (ASCVD).

    Cholesterol Management

    • Focus on LDL-C:
      • Lowering LDL-C levels is the primary goal to reduce the risk of atherosclerotic cardiovascular disease (ASCVD).
    • Non-pharmacological Approaches:
      • Lifestyle modifications such as a healthy diet, physical activity, weight management, and smoking cessation are essential.
    • Monitoring:
      • Regular lipid panel evaluations are necessary to assess therapy effectiveness and make adjustments as needed.

    Target Populations

    • Primary Focus:
      • Adults aged 40–75 with elevated LDL-C levels.
      • Individuals with existing ASCVD.
      • Patients with conditions such as diabetes and low (HDL-C) levels.

    Clinical Trial Design

    • Randomized Controlled Trials (RCTs) are the gold standard for assessing long-term effects of therapies
    • The primary endpoint in trials is change in triglyceride levels
    • Secondary endpoints include cardiovascular events, overall mortality, and quality of life metrics
    • Participants in trials typically have elevated triglyceride levels (> 150 mg/dL)
    • Trials consider comorbidities such as diabetes and cardiovascular disease
    • The necessary sample size and trial duration vary based on the study's objective
    • Typical trial durations range from 6 months to several years.

    Non-statin Therapies

    • Fibrates are effective in lowering triglycerides and can increase HDL cholesterol levels
    • Omega-3 fatty acids, specifically EPA and DHA formulations, are also effective in lowering triglycerides
    • Niacin has been less commonly used due to its side effects
    • PCSK9 inhibitors primarily lower LDL cholesterol levels, but may also have a triglyceride-lowering effect
    • SGLT2 inhibitors have recently been shown as potential triglyceride-lowering agents.

    Hypertriglyceridemia Management

    • Lifestyle modifications are recommended as the first-line therapy for hypertriglyceridemia
    • These modifications include low-carb, low-sugar, and healthy fat diets
    • Increased intake of omega-3 rich foods, particularly fish
    • Regular exercise can significantly reduce triglyceride levels
    • Maintaining a healthy weight is crucial for lowering triglycerides and improving overall health
    • Regular lipid panels are recommended to monitor triglyceride levels and assess treatment efficacy.

    Guideline Implications

    • Practice guidelines prioritize lifestyle modifications as the primary approach to manage hypertriglyceridemia
    • Non-statin therapies are considered for patients who continue to have elevated triglycerides despite lifestyle changes
    • The treatment goal is typically to achieve triglyceride levels below 150 mg/dL
    • Cardiovascular risk assessments are emphasized over just triglyceride levels when making treatment decisions
    • Ongoing clinical trials are expected to influence future guidelines and the development of new therapies.

    Non-Statin Therapies for Hypertriglyceridemia

    • Focus: Trials for non-statin therapies primarily aim to reduce triglyceride levels and cardiovascular events.
    • Types:
      • Fibrates: Lower triglycerides and potentially raise HDL cholesterol.
      • Omega-3 Fatty Acids (EPA & DHA): Reduce triglycerides.
      • Niacin: Reduces triglycerides, but recent trials question its cardiovascular benefits.
      • PCSK9 Inhibitors: Primarily used for LDL cholesterol, but also associated with triglyceride reduction.

    ### Key Trials

    • REDUCE-IT: Icosapent ethyl (EPA) showed significant cardiovascular event reduction in patients with high triglycerides.
    • VA-HIT: Fibrates benefitted patients with low HDL cholesterol.
    • HPS2-THRIVE: Evaluated niacin and its combination with statins for hypertriglyceridemia.

    Risk Factors for Hypertriglyceridemia

    • Common Risk Factors:
      • Obesity and metabolic syndrome
      • Diabetes mellitus and insulin resistance
      • Sedentary lifestyle and poor diet (high in sugars and fats)
      • Genetic predispositions (familial hypertriglyceridemia)
      • Alcohol consumption
      • Certain medications (e.g., corticosteroids, beta-blockers)

    Patient Outcomes

    • Non-Statin Therapy Efficacy:

      • Potential for significant triglyceride reduction (varies by agent).
      • Improved patient outcomes may include reduced risk of pancreatitis.
      • Variable effects on cardiovascular outcomes; some trials report notable reductions.

    • Side Effects and Risks:

      • Fibrates: Risk of muscle-related adverse events, especially with statin use.
      • Omega-3s: Gastrointestinal symptoms like burping or fishy aftertaste.
      • Niacin: Flushing, liver toxicity, and worsening glycemic control in diabetics.

    Treatment Guidelines

    • Recommendations:

      • Lifestyle changes: First-line approach (diet, exercise).
      • Non-Statin therapies:
        • Initiate if triglyceride levels >150 mg/dL for lifestyle modifications.

        • 500 mg/dL for pharmacotherapy to prevent pancreatitis.

      • Individualized therapy: Guided by patient risk profiles and triglyceride levels.

    • Combination Therapies: Non-statin treatments may be combined with statins for better lipid management.

    • Monitoring: Regular follow-up and lipid profile assessment to evaluate therapy efficacy and tolerability. Adjust treatment plans based on clinical response and side effects.

    Hypertriglyceridemia Non-Statin Therapy Trials

    • IMPROVE-IT trial: This trial used ezetimibe in combination with simvastatin to study the effect on major adverse cardiovascular events (MACE) in patients with coronary heart disease.
    • FOURIER trial: This trial used PCSK9 inhibitor (evolocumab) in combination with statins to study the effect on patients with established cardiovascular disease.
    • ODYSSEY trial: This trial used PCSK9 inhibitor (alirocumab) in combination with statins to study the effect on patients with established cardiovascular disease.
    • CLEAR trial: This trial studied the effect of fenofibrate on heart disease in patients with metabolic syndrome.
    • ORION trial: This trial used icosapent ethyl (a type of omega-3 fatty acid) and assessed its effect on cardiovascular disease in patients with elevated triglycerides and low HDL cholesterol.
    • ELIPSE HoFH Trial: This trial studied the effect of inclisiran (a PCSK9 inhibitor) on patients with HoFH (homozygous familial hypercholesterolemia).
    • Reduce-it trial: This trial studied the effect of icosapent ethyl on cardiovascular events in patients with elevated triglycerides and established cardiovascular disease.
    • Strength trial: This trial studied the effect of adding a statin to fenofibrate therapy on triglyceride levels and cardiovascular events in patients with mixed dyslipidemia.
    • Accord Lipid Trial: This trial studied the effect of fenofibrate on cardiovascular events in patients with diabetes and high triglyceride levels.
    • Prominent Trial: This trial studied the effect of fenofibrate on cardiovascular events in patients with diabetes and high triglyceride levels.
    • Aim-High Trial: This trial studied the effect of niacin on cardiovascular events in patients with high cholesterol and low HDL cholesterol.
    • HPS2-THRIVE TRIAL: This trial studied the effect of a combination of omega-3 fatty acids on cardiovascular events in patients with established cardiovascular disease.

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    Related Documents

    Hyperlipidemia Management_Statins_ 2024 STUDENT PDF
    Non Statin Therapy for Hyperlipidemia 2024 Student PDF
    Hyperlipidemia Management Guidelines Summary PDF
    HLD Herbal Slides 2021 PDF

    Description

    Test your knowledge on the pharmacotherapy of hyperlipidemia, including details on statin therapy, PCSK9 inhibitors, and lifestyle modifications. Cover mechanisms of action, indications, common agents, side effects, and monitoring processes essential for effective treatment.

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