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Statins
Statins are first-line therapy for the prevention of atherosclerotic cardiovascular disease (ASCVD).
They reduce LDL cholesterol and lower the risk of:
• Myocardial infarction • Ischemic stroke • Cardiovascular mortality • All-cause mortality (in high-risk populations)
Statins are mortality drugs.
Mechanism of Action
Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis.
Result:
• ↓ Hepatic cholesterol production • ↑ LDL receptor expression • ↑ Clearance of circulating LDL • ↓ Plasma LDL concentration
Primary effect: LDL reduction
Secondary effects: • Mild triglyceride reduction • Modest HDL increase • Plaque stabilization • Reduced vascular inflammation
Statin Intensity
Statins are categorized by expected LDL reduction:
| Intensity | LDL Reduction | Agents |
|---|---|---|
| High-Intensity | ≥50% | Atorvastatin 40–80 mg, Rosuvastatin 20–40 mg |
| Moderate-Intensity | 30–49% | Atorvastatin 10–20 mg, Rosuvastatin 5–10 mg, Simvastatin, Pravastatin |
| Low-Intensity | <30% | Low-dose Simvastatin, Pravastatin |
Clinical selection is based on ASCVD risk.
Indications
Primary Prevention
• Elevated ASCVD risk • LDL ≥190 mg/dL • Diabetes (age 40–75)
Statin intensity is chosen based on risk profile.
Secondary Prevention
Established ASCVD:
• High-intensity statin unless contraindicated • Goal: maximize LDL reduction
Add non-statin therapy if LDL remains above target.
Pharmacokinetics
• Most statins are hepatically metabolized • Many use CYP3A4 (e.g., simvastatin, atorvastatin) • Rosuvastatin and pravastatin have fewer CYP interactions
Evening dosing: • Most useful for shorter-acting statins • Less important for atorvastatin and rosuvastatin
Adverse Effects
1. Myopathy
Spectrum: • Myalgias (most common) • Myositis • Rhabdomyolysis (rare)
Risk increases with: • Drug interactions • High doses • Renal impairment
2. Hepatic Enzyme Elevation
• Mild ALT elevation possible • Routine monitoring not required unless clinically indicated
3. Diabetes Risk
• Slight increase in new-onset diabetes • Benefit outweighs risk in ASCVD patients
Drug Interactions
Higher risk of myopathy with:
• Strong CYP3A4 inhibitors • Fibrates (especially gemfibrozil) • Certain antifungals and macrolides
Rosuvastatin and pravastatin preferred in high interaction risk patients.
Statin Intolerance
True statin intolerance is uncommon.
Management strategies:
• Reduce dose • Switch statin • Alternate-day dosing • Add ezetimibe • Consider PCSK9 inhibitor if high-risk
Clinical Pearls
✔ LDL reduction correlates with event reduction ✔ High-intensity statins reduce events the most ✔ Benefits accumulate over years ✔ Most side effects are manageable ✔ Always weigh risk reduction vs perceived intolerance
Continue exploring lipid therapy:
→ Non-Statin LDL Lowering Agents
Return to lipid module: