Statins

Summary

Statins, also known as HMG-CoA Reductase Inhibitors, are a class of lipid-lowering drugs used to lower cholesterol levels in the bloodstream. These drugs have been shown to decrease mortality in coronary artery disease.

Statins work by inhibiting the conversion of HMG-CoA into mevalonate, which blocks the rate-limiting step of cholesterol production inside the liver. Therefore, statins can decrease hepatic cholesterol synthesis. This reduction of cholesterol production causes cells to respond by increasing LDL receptor recycling, and increasing LDL breakdown.

In lab testing, patients taking statins often experience a rise in HDL levels, a very large fall in LDL levels, and a fall in triglyceride levels.

Side effects of taking statins include hepatotoxicity, as well as myopathy. The risk of myopathy is increased when statins are taken with fibrates or niacin.

Key Points

• Statins (HMG-CoA Reductase Inhibitors)
  • Drug Names (-statin ending)
    • Atorvastatin
    • Simvastatin
    • Lovastatin
    • Pravastatin
    • Rosuvastatin
  • Mechanism
    • Inhibit conversion of HMG-CoA to mevalonate
      • This is the rate-limiting step of cholesterol synthesis to form a cholesterol precursor
      • Decreased hepatic cholesterol production
        • Causes compensatory increase in hepatic clearance of circulating LDL to maintain normal hepatic cholesterol levels
        • Decreased intrahepatic cholesterol
      • Increased LDL-receptor recycling
        • This increases receptor expression at cell surface
      • Increased LDL breakdown
  • Clinical Use
    • Lipid-Lowering Drug (Treats Hyperlipidemia)
      • First-line therapy for reducing blood cholesterol levels
    • Reduces Mortality in patients with Coronary Artery Disease (CAD)
      • Proven to decrease mortality of cardiovascular events along with ACE inhibitors and aspirin
  • Labs
    • ↓↓↓ LDL
    • ↑ HDL
    • ↓ Triglycerides
  • Side Effects
    • Hepatotoxicity (↑ LFTs)
      • Liver function tests like AST and ALT may be elevated
    • Myopathy
      • Risk increased when taken with fibrates or niacin
      • Statins believed to inhibit aerobic respiration in muscle cells
      • Presents with muscle pain and elevated creatine kinase (CK) levels
    • Toxicity increased when taken with CYP Inhibitors
      • Statins are metabolized by CYP enzymes
    • Note: statins are one of the only cholesterol-lowering drugs to decrease gallstone formation
      • Since statins prevent the formation of cholesterol, not the excretion