Statins

Statins are 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.

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

Complete Statin Master Table

Drug	Dose Range	Intensity	LDL Reduction	CYP Metabolism	Lipophilicity
Atorvastatin	10–80 mg	Moderate–High	35–60%	CYP3A4	Lipophilic
Rosuvastatin	5–40 mg	Moderate–High	45–63%	Minimal CYP2C9	Hydrophilic
Simvastatin	10–40 mg	Low–Moderate	25–45%	CYP3A4	Lipophilic
Pravastatin	10–80 mg	Low–Moderate	20–40%	No CYP	Hydrophilic
Lovastatin	10–40 mg	Low–Moderate	25–40%	CYP3A4	Lipophilic
Fluvastatin	20–80 mg	Low–Moderate	20–35%	CYP2C9	Lipophilic
Pitavastatin	1–4 mg	Moderate	30–45%	Minimal CYP	Lipophilic

Intensity Classification (Clinical Anchor)

Intensity	Expected LDL Reduction	Drugs
High-Intensity	≥50%	Atorvastatin 40–80 mg; 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.

Pharmacokinetic Considerations

High Interaction Risk (CYP3A4):

Lower Interaction Risk:

Hydrophilic (less muscle penetration):

Rosuvastatin
Pravastatin

Lipophilic:

Atorvastatin
Simvastatin
Lovastatin
Fluvastatin
Pitavastatin

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 Fibrates (especially Gemfibrozil)

Clinical Strategy

Primary Prevention:

Select statin intensity based on ASCVD risk

Secondary Prevention:

High-intensity statin unless contraindicated
Add Ezetimibe if LDL remains above goal
Consider PCSK9 Inhibitors in very high-risk patients

Statins are foundational therapy. Other lipid agents are additive.

High-Yield 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 with dose adjustment
Discontinuation increases cardiovascular risk

Continue Lipid Therapy:

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