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Statins
Statins are HMG-CoA reductase inhibitors and are first-line therapy for reducing LDL cholesterol and preventing ASCVD.
Primary Outcomes: • ↓ Myocardial infarction • ↓ Ischemic stroke • ↓ Cardiovascular mortality • ↓ All-cause mortality (high-risk patients)
Statins are mortality drugs.
Mechanism of Action
• Inhibit HMG-CoA reductase (rate-limiting step in cholesterol synthesis) • ↓ Hepatic cholesterol production • ↑ LDL receptor expression • ↑ LDL clearance from circulation
Greater LDL reduction → greater event reduction.
Complete Statin Master Table
| Drug | Dose Range | Intensity | LDL ↓ % | CYP Metabolism | Lipophilic vs Hydrophilic | Key Clinical Pearls |
|---|---|---|---|---|---|---|
| Atorvastatin | 10–80 mg | Moderate–High | 35–60% | CYP3A4 | Lipophilic | Strong outcome data; common first choice |
| Rosuvastatin | 5–40 mg | Moderate–High | 45–63% | Minimal CYP2C9 | Hydrophilic | Most potent per mg; fewer interactions |
| Simvastatin | 10–40 mg | Low–Moderate | 25–45% | CYP3A4 | Lipophilic | Avoid 80 mg; high interaction risk |
| Pravastatin | 10–80 mg | Low–Moderate | 20–40% | No CYP | Hydrophilic | Useful in polypharmacy; fewer interactions |
| Lovastatin | 10–40 mg | Low–Moderate | 25–40% | CYP3A4 | Lipophilic | Take with food; interaction risk |
| Fluvastatin | 20–80 mg | Low–Moderate | 20–35% | CYP2C9 | Lipophilic | Less potent; not commonly first-line |
| Pitavastatin | 1–4 mg | Moderate | 30–45% | Minimal CYP | Lipophilic | Lower diabetes signal in some studies |
Intensity Classification (Clinical Decision Anchor)
| Intensity | Expected LDL Reduction | Drugs |
|---|---|---|
| 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, Lovastatin, Pitavastatin |
| Low-Intensity | <30% | Low-dose Simvastatin, Pravastatin, Lovastatin |
Pharmacokinetic Highlights
Highest Interaction Risk (CYP3A4): • Atorvastatin • Simvastatin • Lovastatin
Lower Interaction Risk: • Rosuvastatin • Pravastatin • Pitavastatin
Hydrophilic (less muscle penetration): • Rosuvastatin • Pravastatin
Lipophilic: • Atorvastatin • Simvastatin • Lovastatin • Fluvastatin • Pitavastatin
Class Adverse Effects
Myopathy Spectrum: • Myalgias (most common) • Myositis • Rhabdomyolysis (rare)
Hepatic: • Mild ALT elevation possible
Metabolic: • Slight ↑ risk of new-onset diabetes • Benefit outweighs risk
Risk increases with: • High dose • Drug interactions • Renal impairment • Combination with fibrates (especially gemfibrozil)
Clinical Strategy
Primary Prevention: • Select intensity based on ASCVD risk
Secondary Prevention: • High-intensity statin unless contraindicated • Add Ezetimibe if LDL above goal • Consider PCSK9 Inhibitors in very high-risk patients
High-Yield Clinical Pearls
✔ Greater LDL reduction = greater event reduction ✔ High-intensity statins provide strongest mortality benefit ✔ Rosuvastatin is most potent per mg ✔ Avoid simvastatin 80 mg ✔ Most statin intolerance can be managed ✔ Statins are first-line unless clearly contraindicated
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