CAD prevention

• Classes of lipoproteins


  • Very-low-density lipoproteins (VLDLs)
  • Low-density lipoproteins (LDLs)
  • High-density lipoproteins (HDLs)
• Triglycerides


  Lipid component of VLDLs
• Cholesterol


  Primary core lipid of LDLs, greatest contributor to coronary heart disease (CHD)
• LDLs initiate and fuel development of atherosclerosis
• Role of LDL cholesterol in atherosclerosis

  1. Transport of LDLs from arterial lumen into endothelial cells, then into the space underlying the arterial epithelium

  2. Infiltration of macrophages, T lymphocytes, and other inflammatory mediators
• Atherosclerosis is now considered primarily a chronic inflammatory process, not just a deposit of lipids
• Cholesterol screening recommendations


  • Total cholesterol
  • HDL cholesterol (less than 40 mg/dL: Low to undesirable)
  • LDL cholesterol (less than 100 mg/dL: Desirable)
  • Triglycerides (TGs)
• New ACC/AHA Guidelines for cholesterol screening and treatment
• Statin Benefit Group


  • Individuals with clinical ASCVD
  • Individuals with primary elevations of LDL cholesterol greater than or equal to 190
  • Individuals 40-75 with diabetes and LDL of 70-189
  • Individuals without clinical ASCVD or diabetes who are 40-75 years of age with LDL 70-189 and an estimated 10 year ASCVD risk of 7.5% or greater
• Drugs should be used only if TLCs (therapeutic lifestyle changes) fail
• Drug Therapy: Not First-Line Therapy

  • HMG-CoA reductase inhibitors
  • Bile acid sequestrants
  • Nicotinic acid (niacin)
  • Fibrates (reduce levels of TGs, not LDLs)
• Secondary Treatment Targets


  • Metabolic syndrome
  • High blood glucose
  • High triglycerides
  • High apolipoprotein B
  • Low-HDL cholesterol
  • Small LDL particles
  • Prothrombotic state
  • Proinflammatory state
  • Hypertension
  • High triglycerides (levels above 150 mg/dL)
• Treatment goals for metabolic syndrome are to reduce the risk for atherosclerotic disease and type 2 diabetes, and to increase physical activity
• High LDL is the most significant contributor to cardiovascular disease, but other lipid abnormalities like high total cholesterol, low HDL, and high triglycerides should also be considered
• Drugs can improve lipid profiles, but not all improve clinical outcomes
• HMG-CoA Reductase Inhibitors (Statins)

  • Most effective drugs for lowering LDL
  • Reduction of LDL cholesterol
  • Elevation of HDL cholesterol
  • Reduction of triglyceride levels
  • Nonlipid beneficial cardiovascular actions (promote plaque stability, reduce risk of CV events, increase bone formation)
• Mechanism of cholesterol reduction by statins

  Administer at night
• Therapeutic uses of statins

  • Hypercholesterolemia
  • Primary and secondary prevention of CV events
  • Post-MI therapy
  • Diabetes
• Adverse effects of statins


  • Common: Headache, rash, GI disturbances
  • Rare: Myopathy/rhabdomyolysis, hepatotoxicity, new-onset diabetes
• Statins interact with most other lipid-lowering drugs (except bile acid sequestrants) and drugs that inhibit CYP3A4
• Statin drug selection based on LDL reduction

  • Lovastatin
  • Pravastatin
  • Simvastatin
  • Fluvastatin
  • Atorvastatin
  • Rosuvastatin
  • Pitavastatin
• Statin pharmacokinetics


  • Rosuvastatin (T1/2 20h, bioavailability 20%)
  • Pravastatin (T1/2 1-2h, bioavailability 17%)
  • Atorvastatin (T1/2 14h, bioavailability 14%)
  • Simvastatin (T1/2 1-2h, bioavailability <5%)
• Nicotinic Acid (Niacin)


  • Reduces LDL and TG levels, increases HDL levels more effectively than any other drug
• Bile acid sequestrants are now primarily used as adjuncts to statins, not first-line
• Ezetimibe


  Inhibits cholesterol absorption, reduces total cholesterol, LDL cholesterol, and apolipoprotein B
• Adverse effects of ezetimibe

  • Myopathy
  • Rhabdomyolysis
  • Hepatitis
  • Pancreatitis
  • Thrombocytopenia
• Ezetimibe interacts with statins, fibrates, bile acid sequestrants, and cyclosporine
• Bempedoic Acid [Nexletol]


  New non-statin cholesterol medication approved for patients with familial hypercholesterolemia maxed on statins that need more cholesterol reduction, no data on CV outcomes
• Adverse effects of bempedoic acid include joint swelling or pain, and tendon rupture
• Bempedoic Acid/ezetimibe [Nexilzet]


  For patients with true statin intolerance, does not cause myalgia and lowers LDL by 35%
• Fibric Acid Derivatives (Fibrates)


  • Most effective drugs available for lowering TG levels, can raise HDL cholesterol, little or no effect on LDL cholesterol
• Fibrate drugs in the United States

  • Gemfibrozil [Lopid]
  • Fenofibrate [Tricor, others]
  • Fenofibric acid [TriLipix]
• Therapeutic uses of fibrates

  Reduces high levels of plasma triglycerides (VLDLs), treatment reserved for patients who have not responded to diet modification, less effective than statins in reducing LDL
• Mechanism of action of fibrates


  Appears to interact with a specific receptor subtype (PPAR alpha)
• Adverse effects of gemfibrozil

  • Rashes
  • Gastrointestinal disturbances
  • Gallstones
  • Myopathy
  • Liver injury (hepatotoxic)
• Gemfibrozil can displace warfarin from plasma albumin, requiring frequent INR monitoring
• PCSK9 Inhibitors


  Monoclonal antibodies like alirocumab [Praluent] and evolocumab [Repatha] that lower LDL cholesterol
• Angina pectoris


  Sudden pain beneath the sternum, often radiating to left shoulder and arm, caused by insufficient oxygen supply to the heart to meet oxygen demand
• The two goals of angina drug therapy are prevention of myocardial infarction/death and prevention of myocardial ischemia/anginal pain
• Three families of antianginal agents

  • Organic nitrates (e.g. nitroglycerin)
  • Beta blockers (e.g. metoprolol)
  • Calcium channel blockers (e.g. verapamil)
  • Ranolazine