Atorvastatin

Atorvastatin is a prescription medication belonging to the statin class, marketed under brand names such as Lipitor. It is widely used to manage high cholesterol levels.

This drug is indicated for both primary and secondary prevention of cardiovascular disease by lowering low-density lipoprotein (LDL) cholesterol and triglycerides, while modestly increasing high-density lipoprotein (HDL) cholesterol.

Atorvastatin works by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, which reduces hepatic cholesterol production and increases clearance of LDL from the bloodstream.

The key gene affecting atorvastatin response is SLCO1B1. This gene encodes the OATP1B1 transporter protein, which helps move atorvastatin from the blood into liver cells for metabolism.

Variants in SLCO1B1 can alter transporter function. Reduced-function variants decrease hepatic uptake of the drug, leading to higher blood levels of atorvastatin. Higher circulating levels increase the risk of side effects such as muscle pain. (A transporter is a protein that carries drugs into cells.)

Genetic variations in SLCO1B1 categorize patients into groups based on transporter function. Reduced-function groups (decreased or poor function) experience higher atorvastatin exposure and increased risk of muscle toxicity, while increased or normal function groups have typical drug levels and standard safety profiles.

Increased Function

• Effect on drug levels: Normal atorvastatin exposure
• Clinical consequence: Standard LDL-lowering benefit with typical myopathy risk
• Side effects: Muscle symptoms uncommon and mild, similar to general population

Normal Function

• Effect on drug levels: Normal atorvastatin exposure
• Clinical consequence: Expected cholesterol reduction with routine safety profile
• Side effects: Mild muscle symptoms in a small percentage, as generally seen

Decreased Function

• Effect on drug levels: Increased atorvastatin exposure due to reduced hepatic uptake
• Clinical consequence: Higher risk of myopathy compared to normal function
• Side effects: Muscle pain more frequent, moderate severity, may require dose adjustment

Possible Decreased Function

• Effect on drug levels: Moderately increased atorvastatin exposure
• Clinical consequence: Elevated myopathy risk similar to decreased function
• Side effects: Muscle discomfort with moderate frequency and severity

Poor Function

• Effect on drug levels: Markedly increased atorvastatin exposure
• Clinical consequence: High risk of statin-associated myopathy
• Side effects: Muscle pain and weakness common, may be severe without dose change

Possible Poor Function

• Effect on drug levels: Significantly increased atorvastatin exposure
• Clinical consequence: Elevated risk of muscle toxicity similar to poor function
• Side effects: Frequent muscle symptoms, moderate to severe in some cases

Indeterminate

• Effect on drug levels: Unknown
• Clinical consequence: No specific guidance available
• Side effects: Standard monitoring recommended

Not available

• Effect on drug levels: Unknown
• Clinical consequence: No specific guidance available
• Side effects: Standard monitoring recommended

The following dosing guidelines are based on the CPIC guideline for SLCO1B1 and atorvastatin.

SLCO1B1 Dosing Guideline

Phenotype	Clinical Consequence	Guideline Recommendation
Increased Function	Normal myopathy risk	Prescribe desired starting dose and adjust doses of atorvastatin based on disease-specific guidelines.
Normal Function	Normal myopathy risk	Prescribe desired starting dose and adjust doses of atorvastatin based on disease-specific guidelines.
Decreased Function	Increased atorvastatin exposure as compared with normal function, which may translate to increased myopathy risk.	Prescribe ≤40 mg as a starting dose and adjust doses based on disease-specific guidelines. If dose >40 mg is needed for desired efficacy, consider combination therapy (atorvastatin plus nonstatin therapy).
Possible Decreased Function	Increased atorvastatin exposure as compared with normal function, which may translate to increased myopathy risk.	Prescribe ≤40 mg as a starting dose and adjust doses based on disease-specific guidelines. If dose >40 mg is needed for desired efficacy, consider combination therapy (atorvastatin plus nonstatin therapy).
Poor Function	Increased atorvastatin exposure as compared with normal and decreased function, which may translate to increased myopathy risk.	Prescribe ≤20 mg as a starting dose and adjust doses based on disease-specific guidelines. If dose >20 mg is needed for desired efficacy, consider rosuvastatin or combination therapy.
Possible Poor Function	Increased atorvastatin exposure as compared with normal and decreased function, which may translate to increased myopathy risk.	Prescribe ≤20 mg as a starting dose and adjust doses based on disease-specific guidelines. If dose >20 mg is needed for desired efficacy, consider rosuvastatin or combination therapy.
Indeterminate	No CPIC guidance for this phenotype	Initiate therapy with recommended starting dose.
Not available	No CPIC guidance for this phenotype	Initiate therapy with recommended starting dose.

Examples from guidelines include considering rosuvastatin as an alternative statin or adding nonstatin lipid-lowering therapies if higher LDL reduction is required and myopathy risk is elevated.

• CPIC – CPIC Guideline for Statins