HMG-CoA Reductase Inhibitors (FETT)

Lipid-regulating drugs

SIMVASTATIN

ATORVASTATIN

Competitive inhibition of HMG-CoA reductase renders this enzyme unable to convert HMG-CoA to mevalonate (the rate-limiting step of cholesterol synthesis) → reduced intrahepatic cholesterol biosynthesis → upregulation of expression of LDL receptor gene via sterol regulatory element-binding protein (SREBP) → increased LDL recycling and: [2]

• ↓↓ LDL cholesterol

• ↑ HDL cholesterol

• ↓ Triglyceride level

• ↓ C-reactive protein

• ↑ Plaque stabilization

• ↑ Anti-inflammatory effect

• Antioxidant effect and improved endothelial function of coronary arteries

• General (common): headache and gastrointestinal symptoms (e.g., constipation, diarrhea, flatulence)

• Hepatic: (up to 3% of patients) ↑ LFTs due to the involvement of cytochrome P450 systems (CYP3A4 and CYP2C9) in the breakdown of statins

• Muscular: Statins decrease the synthesis of coenzyme Q10 and impair energy production within the muscle.

  • Myalgia (muscle pain): continue treatment as long as creatinine phosphokinase (CK) remain normal

  • Statin-associated myopathy

    • Muscle pain and weakness, especially when used alongside fibrates or niacin

    • Myositis: ↑ CK

    • May progress to rhabdomyolysis: rare but severe side-effect that may lead to myoglobulinuria → AKI (↑ BUN and ↑ creatinine)

    • Management: discontinue statin therapy for 2–4 weeks; start treatment with a low-dose statin (e.g., pravastatin or fluvastatin) once symptoms have resolved

• High-intensity statins

  • Patients with a clinical atherosclerotic cardiovascular disease (includes coronary artery disease, stroke, and peripheral arterial disease)

  • Patients with LDL cholesterol elevated ≥ 190 mg/dL (first-line treatment)

  • Patients with diabetes and multiple risk factors

• Low- to moderate-intensity statins: primary prevention of ASCVD ]

  • Patients aged 40–75 with no history of CVD, ≥ 1 CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), and calculated 10-year ASCVD risk ≥ 10%

  • Consider in patients aged 40–75 with no history of CVD, ≥ 1 CVD risk factors, and calculated 10-year ASCVD risk 7.5–10%

• Hypersensitivity

• Active liver disease

• Muscle disorder

• Pregnancy, breastfeeding

• Other lipid-lowering agents

  • Fibrates

  • Nicotinic acid

  • Both agents may also cause myopathy → concomitant use with statins further increases the risk of myopathy!

• CYP3A4 inhibitors

  • HIV/HCV protease inhibitors

  • Macrolides (especially erythromycin and clarithromycin)

  • Azole antifungals

  • Cyclosporine

• Warfarin

• Ideally administered in the evenings (especially simvastatin)

• Combination therapy with bile acid resins has a stronger hypolipidemic effect compared to treatment with statins alone (both groups of drugs increase LDL receptor expression)