Lipid Therapy

Categories: Cardiovascular-Renal

  • Elevated LDL-C
    • Diet: Trans/Saturated Fats, Weight gain, Anorexia, Alcohol
    • Drug: Diuretics, Cyclosporines, Glucocorticoids, Amiodarone
    • Diseases: Biliary Obstruction, Nephrotic Syndrome
    • Other: Hypothyroidism, Obesity, Pregnancy
  • Elevated Triglycerides
    • Diet: Weight gain, Very low fat diets, High intake of refined carbs, Excessive Alcohol intake
    • Drug: Oral estrogens, Glucocorticoids, Bile Acid Sequestrants, Protease inhibitors, Retinoic acid, Anabolic steroids, Sirolimus, Raloxifene, Tamoxifen, BB (not carvedilol), Thiazides
    • Diseases: Nephrotic Syndrome, Chronic Renal Failure, Lipodystrophies
    • Other: Poorly controlled diabetes, Hypothyroidism, Obesity, Pregnancy
  • Dietary fat has a greater impact on serum LDL-C than does dietary cholesterol intake
    • Fats should be limited to <30% of total caloric intake
    • Saturated fats should be limited to <10% of calories (7% if LDL-C above goal)
  • Higher-Risk
    • The following factors that may be considered for the identification of higher-risk patients with clinical CV disease:
      • Age ≥65 years, prior MI or non-hemorrhagic stroke, current daily cigarette smoking, symptomatic PVD with prior MI or stroke, history of non-MI related coronary revascularization, residual coronary artery disease with ≥40% stenosis in ≥2 large vessels, HDL <40 mg/dL for men and <50 mg/dL for women, hs-CRP ≥2 mg/L, or metabolic syndrome
  • Liver
    • Statins (HMG-CoA reductase inhibitors, LDL)
      • MOA: RLS in intracellular biosynthesis of cholesterol (competitive inhibition)
        • Increases LDL receptors on liver cell membranes
          • Remove circulating LDL and digest it
          • Reduces serum w/ minimal liver LDL change
        • Decrease CoQ10 synthesis (ubiquinone)
        • Statins metabolized by CYP450 3A4
          • Lovastatin, simvastatin, atorvastatin
      • Benefits
        • Plaque stabilization
        • Inflammation Reduction, decrease CRP
        • Improve endothelial function
        • Decreased Thrombogenicity
      • Potency:
        • High Potency: lower LDL by ≥50%
          • Large LDL Decrease (20-60%, 1st line)
          • Doubling dose adds 6% effect
      • Rosuvastatin (Crestor)
        • High: 20-40mg
        • Moderate: 5-10mg
        • CKD ≥3 or Dialysis: 10mg
        • Can be used in Cirrhosis
      • Atorvastatin (Lipitor)
        • High: 40-80mg
        • Moderate: 10-20mg
        • CKD ≥3 or Dialysis: 20mg
        • Lipophilic, not renally cleared
      • Simvastatin (Zocor)
        • Moderate: 20-40mg
        • Low: 10mg
        • CKD ≥3 or Dialysis: 20mg
        • Lipophilic, not renally cleared
      • Pravastatin (Pravachol)
        • Moderate: 40-80mg
        • Low: 10-20mg
        • CKD ≥3 or Dialysis: 40mg
        • Least muscle SE, preferred in elevated LFTs
        • Not renally cleared, can be used in Cirrhosis
      • Lovastatin (Mevachor)
        • Moderate: 40mg
        • Low: 20mg
        • CKD ≥3 or Dialysis: Not evaluated
        • Lipophilic
      • Fluvastatin
        • Moderate: 80mg
        • Low: 20-40mg
        • CKD ≥3 or Dialysis: 80mg
        • Least muscle SE, not renally cleared
      • Pitavastatin
        • Moderate: 2-4mg
        • Low: 1mg
        • CKD ≥3 or Dialysis: 2mg
      • Most effective, first line to lower cholesterol and LDL
        • Moderate HDL increase
        • Moderate Triglyceride Decrease
      • Trials
        • IMPROVE-IT (2015)
          • Adding ezetimibe to statin further reduces CV events in the population, suggesting the maximal LDL reduction is the key mech
      • SE: Hepatotoxicity
        • If AST/ALT ≥ 3x ULN, reduce or switch
        • Myalgias (symmetrical proximal muscle weakness or tenderness)
          • 1-10%, mc side effect
        • Myositis/Myopathy
          • Elevated CK
        • Rhabdomyolysis
          • 1%, CK ≥ 10x ULN + Renal injury
        • Statin-associated autoimmune myopathy (HMGCR antibodies)
        • High Intensity
          • Renal Dysfunction
            • More common w/Rosuvastatin/Simvastatin
            • Proteinuria, hematuria, AKI
            • Switch to Atorvastatin, Fluvastatin, pravastatin
          • Diabetes Mellitus
            • Increased plasma glucose concentrations
      • CI: Pregnancy, Lactation, Acute liver failure/decompensated cirrhosis
        • VATER association, TE fistulas, anal atresias
      • Interactions
        • Amlodipine, diltiazem, verapamil with simvastatin or lovastatin increases risk of toxicity
        • Gemfibrozil: Increased risk for muscle toc
        • Colestipol and antacids decrease plasma concentration
        • Amiodarone, cranberry, grapefruit
      • Monitoring
        • Lipid profile at baseline, then 2 months after
        • LFTs and TSH at baseline, +/- CK level
    • Niacin
      • Drugs: Niacin
      • Lipolysis Decreased in Adipose Tissues
        • Moderate LDL Decrease
        • Large HDL Increase
        • Moderate Triglycerides Decrease
      • Flushing and pruritis is caused by prostaglandin-induced peripheral vasodilation
        • Low dose aspirin may reduce symptoms
    • Lomitapide (Juxtapid)
      • MTTP Inhibitors (VLDL)
    • Mitratapide (Yarvitan)
      • MTTP Inhibitors (VLDL)
  • GI Tract
    • Ezetimibe (Zetia)
      • Cholesterol Absorption Inhibitor at Intestinal Border, NPC1L1
      • Moderate LDL Decrease (15-20%, 2nd line)
      • May be used in ASCVD w/very high risk on max statin with LDL ≥70 or non-HDL ≥100
      • HDL Unchanged
      • Triglycerides Unchanged
    • Bile Acid Sequestrants/Resins (LDL)
      • Drugs: Cholestyramine, Colesevelam (Welchol), Colestipol
      • Inhibits reabsorption of bile acids, decreasing lipoprotein levels
      • Alone or in combo with Stains
      • Moderate LDL Decrease
      • Mild HDL Increase
      • Triglycerides Unchanged-Increased
  • Blood Vessels
    • Fibrates (Lipoprotein lipolysis Induction, PPAR)
      • Drugs: Fenofibrate (Tricor), Gemfibrozil (Lopid)
        • Not as favorable CV effects as statins or niacin
      • Moderate LDL Decrease
      • Moderate HDL Increase
      • Large Triglycerides Decrease (35-50%)
    • PCSK9 Inhibitors (LDL)
      • MOA: Proprotein convertase subtilisin/kexin type 9 (PCSK9), produced by liver that leads to degradation of hepatocyte LDL receptors via internalization and destruction
      • Evolocamab
      • Alirocumab (Praluent)
      • Trials
        • FOURIER (2017)
          • Among patients with clinical atherosclerotic disease and LDL ≥ 70 despite high or moderate intensity statin therapy (70% high intensity), Evolocumab resulted in an absolute 1.5% reduction in MACE at 26m. Mainly from reduction in nonfatal MI, stroke, and revascularization.
            • No mortality benefits
            • Absolute reduction in CVE was greater with more advanced CKD
        • ODESSEY OUTCOMES (2021)
          • In recent ACS and LDL ~70 on optimized statin therapy, PCSK9 inhibitors provide clinical benefit only when lp(a) is at least mildly elevated.
          • Mortality benefit in the long term
      • SE: Injection site reaction

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