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cardio:lipids:statins

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cardio:lipids:statins [2026/02/12 22:26] – created andrew2393cnscardio:lipids:statins [2026/02/13 17:45] (current) – andrew2393cns
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 ====== Statins ====== ====== Statins ======
  
-Statins are first-line therapy for the prevention of atherosclerotic cardiovascular disease (ASCVD).+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 reduce LDL cholesterol and lower the risk of:+They are outcome-driven therapies.
  
-• Myocardial infarction   +Primary Benefits: 
-• Ischemic stroke   +  * ↓ Myocardial infarction 
-• Cardiovascular mortality   +  * ↓ Ischemic stroke 
-• All-cause mortality (in high-risk populations)  +  * ↓ Cardiovascular mortality 
 +  * ↓ All-cause mortality (high-risk patients)
  
-Statins are mortality drugs.+Greater LDL reduction correlates directly with greater event reduction.
  
-----+--------------------------------------------------------------------
  
 ===== Mechanism of Action ===== ===== Mechanism of Action =====
  
-Statins inhibit **HMG-CoA reductase**, the rate-limiting enzyme in hepatic cholesterol synthesis.+Primary Target: 
 +  * HMG-CoA reductase (rate-limiting step in hepatic cholesterol synthesis)
  
-Result:+Physiologic Effects: 
 +  * ↓ Hepatic cholesterol production 
 +  * ↑ LDL receptor expression 
 +  * ↑ Clearance of circulating LDL
  
-• ↓ Hepatic cholesterol production   +Net Result: 
-• ↑ LDL receptor expression   +  * ↓ LDL cholesterol (dose-dependent) 
-• ↑ Clearance of circulating LDL   +  * Plaque stabilization 
-• ↓ Plasma LDL concentration  +  * Reduced inflammatory signaling
  
-Primary effect: LDL reduction+--------------------------------------------------------------------
  
-Secondary effects: +===== Complete Statin Master Table =====
-• Mild triglyceride reduction   +
-• Modest HDL increase   +
-• Plaque stabilization   +
-• Reduced vascular inflammation  +
  
-----+^ 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 |
  
-===== Statin Intensity =====+--------------------------------------------------------------------
  
-Statins are categorized by expected LDL reduction:+===== Intensity Classification (Clinical Anchor) =====
  
-^ Intensity ^ LDL Reduction ^ Agents ^ +^ Intensity ^ Expected LDL Reduction ^ Drugs ^ 
-| High-Intensity | ≥50% | Atorvastatin 40–80 mg, Rosuvastatin 20–40 mg | +| High-Intensity | ≥50% | [[cardio:lipids:atorvastatin|Atorvastatin]] 40–80 mg; [[cardio:lipids:rosuvastatin|Rosuvastatin]] 20–40 mg | 
-| Moderate-Intensity | 30–49% | Atorvastatin 10–20 mg, Rosuvastatin 5–10 mg, Simvastatin, Pravastatin | +| Moderate-Intensity | 30–49% | Lower-dose Atorvastatin; Rosuvastatin 5–10 mg; Simvastatin; Pravastatin; Lovastatin; Pitavastatin | 
-| Low-Intensity | <30% | Low-dose Simvastatin, Pravastatin |+| Low-Intensity | <30% | Low-dose Simvastatin; Pravastatin; Lovastatin |
  
-Clinical selection is based on ASCVD risk.+Clinical rule: 
 +Intensity selection is based on ASCVD risk — not LDL number alone.
  
-----+--------------------------------------------------------------------
  
-===== Indications =====+===== Pharmacokinetic Considerations =====
  
-==== Primary Prevention ====+High Interaction Risk (CYP3A4): 
 +  * [[cardio:lipids:atorvastatin|Atorvastatin]] 
 +  * [[cardio:lipids:simvastatin|Simvastatin]] 
 +  * [[cardio:lipids:lovastatin|Lovastatin]]
  
-• Elevated ASCVD risk   +Lower Interaction Risk: 
-• LDL ≥190 mg/dL   +  * [[cardio:lipids:rosuvastatin|Rosuvastatin]] 
-• Diabetes (age 40–75)  +  * [[cardio:lipids:pravastatin|Pravastatin]] 
 +  * [[cardio:lipids:pitavastatin|Pitavastatin]]
  
-Statin intensity is chosen based on risk profile.+Hydrophilic (less muscle penetration): 
 +  * Rosuvastatin 
 +  * Pravastatin
  
-----+Lipophilic: 
 +  * Atorvastatin 
 +  * Simvastatin 
 +  * Lovastatin 
 +  * Fluvastatin 
 +  * Pitavastatin
  
-==== Secondary Prevention ====+--------------------------------------------------------------------
  
-Established ASCVD:+===== Class Adverse Effects =====
  
-• High-intensity statin unless contraindicated   +Muscle: 
-• Goal: maximize LDL reduction  +  * Myalgias (most common) 
 +  * Myositis 
 +  * Rhabdomyolysis (rare)
  
-Add non-statin therapy if LDL remains above target.+Hepatic: 
 +  * Mild ALT elevation
  
-----+Metabolic: 
 +  * Slight ↑ risk of new-onset diabetes 
 +  * Cardiovascular benefit outweighs risk
  
-===== Pharmacokinetics =====+Risk Factors for Myopathy: 
 +  * High-dose therapy 
 +  * Drug interactions 
 +  * Renal impairment 
 +  * Combination with [[cardio:lipids:fibrates:start|Fibrates]] (especially [[cardio:lipids:gemfibrozil|Gemfibrozil]])
  
-• Most statins are hepatically metabolized   +--------------------------------------------------------------------
-• Many use CYP3A4 (e.g., simvastatin, atorvastatin)   +
-• Rosuvastatin and pravastatin have fewer CYP interactions  +
  
-Evening dosing: +===== Clinical Strategy =====
-• Most useful for shorter-acting statins   +
-• Less important for atorvastatin and rosuvastatin  +
  
-----+Primary Prevention: 
 +  * Select statin intensity based on ASCVD risk
  
-===== Adverse Effects =====+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
  
-==== 1. Myopathy ====+Statins are foundational therapy. Other lipid agents are additive.
  
-Spectrum: +--------------------------------------------------------------------
-• Myalgias (most common)   +
-• Myositis   +
-• Rhabdomyolysis (rare)  +
  
-Risk increases with: +===== High-Yield Pearls =====
-• Drug interactions   +
-• High doses   +
-• Renal impairment  +
  
-----+  * 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
  
-==== 2. Hepatic Enzyme Elevation ====+--------------------------------------------------------------------
  
-• Mild ALT elevation possible   +Continue Lipid Therapy:
-• 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: +
- +
-→ [[cardio:lipids:nonstatins|Non-Statin LDL Lowering Agents]] +
- +
-Return to lipid module:+
  
 +→ [[cardio:lipids:ezetimibe|Ezetimibe]]  
 +→ [[cardio:lipids:pcsk9:start|PCSK9 Inhibitors]]  
 → [[cardio:lipids:start|Back to Antilipemics]] → [[cardio:lipids:start|Back to Antilipemics]]
cardio/lipids/statins.1770935161.txt.gz · Last modified: by andrew2393cns