====== Statins ======

Statins are [[cardio:lipids:start|HMG-CoA reductase inhibitors]] and are first-line therapy for LDL reduction and prevention of atherosclerotic cardiovascular disease (ASCVD).

They are outcome-driven therapies.

Primary Benefits:
  * ↓ Myocardial infarction
  * ↓ Ischemic stroke
  * ↓ Cardiovascular mortality
  * ↓ All-cause mortality (high-risk patients)

Greater LDL reduction correlates directly with greater event reduction.

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===== Mechanism of Action =====

Primary Target:
  * HMG-CoA reductase (rate-limiting step in hepatic cholesterol synthesis)

Physiologic Effects:
  * ↓ Hepatic cholesterol production
  * ↑ LDL receptor expression
  * ↑ Clearance of circulating LDL

Net Result:
  * ↓ LDL cholesterol (dose-dependent)
  * Plaque stabilization
  * Reduced inflammatory signaling

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===== Complete Statin Master Table =====

^ Drug ^ Dose Range ^ Intensity ^ LDL Reduction ^ CYP Metabolism ^ Lipophilicity ^
| [[cardio:lipids:atorvastatin|Atorvastatin]] | 10–80 mg | Moderate–High | 35–60% | CYP3A4 | Lipophilic |
| [[cardio:lipids:rosuvastatin|Rosuvastatin]] | 5–40 mg | Moderate–High | 45–63% | Minimal CYP2C9 | Hydrophilic |
| [[cardio:lipids:simvastatin|Simvastatin]] | 10–40 mg | Low–Moderate | 25–45% | CYP3A4 | Lipophilic |
| [[cardio:lipids:pravastatin|Pravastatin]] | 10–80 mg | Low–Moderate | 20–40% | No CYP | Hydrophilic |
| [[cardio:lipids:lovastatin|Lovastatin]] | 10–40 mg | Low–Moderate | 25–40% | CYP3A4 | Lipophilic |
| [[cardio:lipids:fluvastatin|Fluvastatin]] | 20–80 mg | Low–Moderate | 20–35% | CYP2C9 | Lipophilic |
| [[cardio:lipids:pitavastatin|Pitavastatin]] | 1–4 mg | Moderate | 30–45% | Minimal CYP | Lipophilic |

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===== Intensity Classification (Clinical Anchor) =====

^ Intensity ^ Expected LDL Reduction ^ Drugs ^
| High-Intensity | ≥50% | [[cardio:lipids:atorvastatin|Atorvastatin]] 40–80 mg; [[cardio:lipids:rosuvastatin|Rosuvastatin]] 20–40 mg |
| Moderate-Intensity | 30–49% | Lower-dose Atorvastatin; Rosuvastatin 5–10 mg; Simvastatin; Pravastatin; Lovastatin; Pitavastatin |
| Low-Intensity | <30% | Low-dose Simvastatin; Pravastatin; Lovastatin |

Clinical rule:
Intensity selection is based on ASCVD risk — not LDL number alone.

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===== Pharmacokinetic Considerations =====

High Interaction Risk (CYP3A4):
  * [[cardio:lipids:atorvastatin|Atorvastatin]]
  * [[cardio:lipids:simvastatin|Simvastatin]]
  * [[cardio:lipids:lovastatin|Lovastatin]]

Lower Interaction Risk:
  * [[cardio:lipids:rosuvastatin|Rosuvastatin]]
  * [[cardio:lipids:pravastatin|Pravastatin]]
  * [[cardio:lipids:pitavastatin|Pitavastatin]]

Hydrophilic (less muscle penetration):
  * Rosuvastatin
  * Pravastatin

Lipophilic:
  * Atorvastatin
  * Simvastatin
  * Lovastatin
  * Fluvastatin
  * Pitavastatin

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===== Class Adverse Effects =====

Muscle:
  * Myalgias (most common)
  * Myositis
  * Rhabdomyolysis (rare)

Hepatic:
  * Mild ALT elevation

Metabolic:
  * Slight ↑ risk of new-onset diabetes
  * Cardiovascular benefit outweighs risk

Risk Factors for Myopathy:
  * High-dose therapy
  * Drug interactions
  * Renal impairment
  * Combination with [[cardio:lipids:fibrates:start|Fibrates]] (especially [[cardio:lipids:gemfibrozil|Gemfibrozil]])

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===== Clinical Strategy =====

Primary Prevention:
  * Select statin intensity based on ASCVD risk

Secondary Prevention:
  * High-intensity statin unless contraindicated
  * Add [[cardio:lipids:ezetimibe|Ezetimibe]] if LDL remains above goal
  * Consider [[cardio:lipids:pcsk9:start|PCSK9 Inhibitors]] in very high-risk patients

Statins are foundational therapy. Other lipid agents are additive.

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===== High-Yield Pearls =====

  * Greater LDL reduction = greater event reduction
  * High-intensity statins provide strongest mortality benefit
  * [[cardio:lipids:rosuvastatin|Rosuvastatin]] is most potent per mg
  * Avoid simvastatin 80 mg
  * Most statin intolerance can be managed with dose adjustment
  * Discontinuation increases cardiovascular risk

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Continue Lipid Therapy:

→ [[cardio:lipids:ezetimibe|Ezetimibe]]  
→ [[cardio:lipids:pcsk9:start|PCSK9 Inhibitors]]  
→ [[cardio:lipids:start|Back to Antilipemics]]