The Statin-Intolerant Patient: Is it Really the Muscles? The Role of SLCO1B1

A Perfect Example of Pharmacogenetics in Action

Dr Neeraj Manikath , claude.ai

Abstract

Statin-associated muscle symptoms (SAMS) represent a significant clinical challenge, affecting 7-29% of patients and leading to treatment discontinuation, elevated LDL cholesterol, and increased cardiovascular risk. The discovery that genetic variants in SLCO1B1, encoding the hepatic uptake transporter OATP1B1, profoundly influence statin pharmacokinetics has transformed our understanding of statin intolerance. This review examines the mechanistic basis of SLCO1B1-mediated statin intolerance, genotype-phenotype correlations, practical dosing strategies based on genetic information, cost-effectiveness considerations, and implementation guidance for clinical practice. As a paradigm of precision medicine, SLCO1B1 pharmacogenetics provides actionable insights that can improve patient outcomes and medication adherence.

Introduction: The Burden of Statin Intolerance

Statins remain the cornerstone of cardiovascular disease prevention and treatment, with proven efficacy in reducing morbidity and mortality. However, the clinical promise of these medications is often undermined by patient intolerance. While randomized controlled trials report adverse event rates similar to placebo, real-world observational studies paint a different picture, with SAMS occurring in 7-29% of patients. These symptoms range from mild myalgias to rare but life-threatening rhabdomyolysis.

The consequences of statin intolerance extend beyond patient discomfort. Discontinuation leads to inadequate LDL cholesterol control, and patients who discontinue statins face significantly higher rates of cardiovascular events and death. Furthermore, the trial-and-error approach to managing intolerance creates frustration for both patients and clinicians, often resulting in complete abandonment of lipid-lowering therapy.

Enter pharmacogenetics: the SLCO1B1 gene emerged as a game-changer in 2008 when a genome-wide association study identified a specific variant that dramatically increased the risk of simvastatin-induced myopathy. This discovery provided the biological plausibility that had been missing and opened the door to precision statin therapy.

The Pharmacokinetics Simplified: How the SLCO1B1 Transporter Affects Statin Levels

The Hepatic Uptake Gateway

Understanding SLCO1B1 pharmacogenetics requires a basic grasp of statin pharmacokinetics. For statins to exert their therapeutic effect, they must first reach their site of action: the liver. This journey from the portal circulation into hepatocytes is not passive diffusion but rather an active transport process mediated primarily by the organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the SLCO1B1 gene located on chromosome 12.

OATP1B1 is expressed on the sinusoidal (basolateral) membrane of hepatocytes and functions as an influx transporter. It recognizes a broad range of amphipathic anions with molecular weights exceeding 350 Da—a description that fits most statins perfectly. Once statins enter the hepatocyte via OATP1B1, they inhibit HMG-CoA reductase, undergo metabolism (primarily via CYP3A4 for lipophilic statins), and are subsequently excreted via biliary pathways.

The Consequence of Impaired Transport

When OATP1B1 function is reduced—whether through genetic variation or drug-drug interactions—statins accumulate in the systemic circulation rather than being efficiently extracted by the liver. This has two critical consequences:

Reduced hepatic efficacy: Less drug reaches the target organ, potentially diminishing LDL-lowering effectiveness
Increased systemic exposure: Higher plasma concentrations mean greater exposure of peripheral tissues, particularly skeletal muscle, to statins

It is this second consequence that appears to drive SAMS. The prevailing hypothesis suggests that elevated systemic statin concentrations lead to muscle toxicity through mechanisms that may include mitochondrial dysfunction, disruption of cellular membrane integrity, and interference with cellular energy metabolism.

Quantifying the Pharmacokinetic Impact

The magnitude of SLCO1B1 genetic variation on statin pharmacokinetics is substantial. In single-dose studies comparing individuals homozygous for the reduced-function variant (CC genotype at rs4149056) versus those with normal function (TT genotype), the area under the curve (AUC) increases are dramatic:

Simvastatin acid: 221% increase
Pitavastatin: 162-191% increase
Atorvastatin: 144% increase
Pravastatin: 57-130% increase
Rosuvastatin: 62-117% increase

These are not trivial differences. A more than doubling of drug exposure for simvastatin in poor metabolizers explains why this particular statin has been so strongly associated with genetic risk.

Genotype-Phenotype Correlation: What the 1/1, 1/5, and 5/5 Results Mean for Myalgia Risk

Understanding the Star Allele Nomenclature

SLCO1B1 exhibits considerable genetic variability, with over 40 identified nonsynonymous variants. However, two single nucleotide polymorphisms (SNPs) have emerged as clinically most relevant:

rs2306283 (c.388A>G): Also called Asn130Asp, associated with *1b allele, present in approximately 40% of Caucasians, 60% of Asians, and 75% of African-Americans. This variant appears to slightly increase OATP1B1 function.
rs4149056 (c.521T>C): Also called Val174Ala, associated with *5 allele, present in approximately 15% of Caucasians and Asians but only 2% of African-Americans. This variant significantly decreases OATP1B1 function.

These two SNPs combine to form haplotypes with distinct functional consequences:

SLCO1B1*1A: Wild-type (388A-521T) - normal function
SLCO1B1*1B: (388G-521T) - increased function
SLCO1B1*5: (388A-521C) - decreased function
SLCO1B1*15: (388G-521C) - decreased function

Clinical Risk Stratification

The Clinical Pharmacogenetics Implementation Consortium (CPIC) has established a functional phenotype classification based on diplotypes:

Normal Function: *1A/*1A, *1A/*1B, *1B/*1B

Patients with these genotypes have fully functional or enhanced OATP1B1 activity
Standard statin therapy can be prescribed without genetic concerns
Represents approximately 65-70% of Caucasian populations

Decreased Function: *1A/*5, *1A/*15, *1B/*5, *1B/*15

One functional and one reduced-function allele
Moderately increased risk of SAMS with certain statins
Represents approximately 25-30% of Caucasian populations

Poor Function: *5/*5, *5/*15, *15/*15

Two reduced-function alleles
Significantly increased risk of SAMS
Represents approximately 2.5-4% of Caucasian populations

The Numbers Behind the Risk

The landmark SEARCH trial quantified these risks precisely for simvastatin-induced myopathy. Compared to individuals with the TT genotype (normal function), those heterozygous for the C variant had a 4.5-fold increased risk, while CC homozygotes had a staggering 17-fold increased risk of myopathy when taking 80 mg simvastatin.

More recent real-world studies have confirmed and extended these findings. In the Go-DARTS study of over 2,000 patients with diabetes, individuals with poor function genotypes showed significantly higher rates of statin discontinuation, switching, or dose reduction—a composite endpoint serving as a proxy for intolerance. The effect was dose-dependent, being most pronounced with simvastatin doses ≥40 mg.

Beyond Simvastatin: Statin-Specific Risks

Not all statins are created equal regarding SLCO1B1-mediated risk. The genetic effect appears strongest for:

Simvastatin: Highest risk, particularly at doses ≥40 mg
Atorvastatin: Moderate risk, primarily at higher doses
Pravastatin: Lower risk, though some effect demonstrated
Rosuvastatin: Minimal to moderate risk
Fluvastatin: Minimal risk (primarily metabolized by CYP2C9, not heavily dependent on OATP1B1)
Pitavastatin: Moderate risk based on pharmacokinetic data

This differential risk profile provides the foundation for genotype-guided prescribing.

A Practical Dosing Guide: Which Statins and What Doses to Choose for Each Genotype

The CPIC Framework for Clinical Decision-Making

The 2022 CPIC guideline provides comprehensive recommendations that balance cardiovascular benefit against SAMS risk. The approach is nuanced, considering both the SLCO1B1 genotype and the desired intensity of lipid lowering.

For Patients with Normal Function (1A/1A, 1A/1B, 1B/1B):

Low-Intensity Therapy Needed:

All statins at standard doses are appropriate
No genetic constraints on prescribing

Moderate-Intensity Therapy Needed:

All statins including simvastatin 20-40 mg are appropriate
Standard prescribing practices apply

High-Intensity Therapy Needed:

Simvastatin 40-80 mg can be prescribed
Atorvastatin 40-80 mg is preferred
Rosuvastatin 20-40 mg is preferred

For Patients with Decreased Function (1A/5, 1A/15, 1B/5, 1B/15):

Low-Intensity Therapy Needed:

All statins at lower doses are appropriate
Pravastatin 10-20 mg
Rosuvastatin 5-10 mg
Atorvastatin 10-20 mg
Simvastatin 10-20 mg (use with caution)

Moderate-Intensity Therapy Needed:

Preferred: Pravastatin 40-80 mg, Rosuvastatin 5-10 mg, Fluvastatin 40-80 mg
Use with caution: Atorvastatin 10-20 mg, Simvastatin 20-40 mg
Avoid: Simvastatin >40 mg

High-Intensity Therapy Needed:

Preferred: Rosuvastatin 20-40 mg, Atorvastatin 40-80 mg (with caution)
Avoid: Simvastatin 40-80 mg

For Patients with Poor Function (5/5, 5/15, 15/15):

Low-Intensity Therapy Needed:

Pravastatin 10-20 mg (preferred)
Rosuvastatin 5-10 mg (preferred)
Fluvastatin 20-40 mg (preferred)

Moderate-Intensity Therapy Needed:

Preferred: Pravastatin 40-80 mg, Rosuvastatin 5-10 mg, Fluvastatin 40-80 mg
Avoid: Simvastatin at any dose, Atorvastatin >20 mg

High-Intensity Therapy Needed:

Preferred: Rosuvastatin 20-40 mg
Consider combination therapy: low-dose statin plus ezetimibe or PCSK9 inhibitor
Avoid: Simvastatin at any dose

Special Considerations for Patients Already on Therapy

For patients already tolerating a statin when genetic results become available:

If on therapy <4 weeks without symptoms: Consider switching to lower-risk options if genotype indicates moderate or high risk
If on therapy 4 weeks to 1 year without symptoms: Continue current therapy if moderate risk; consider switching if high risk
If on therapy >1 year without symptoms: Generally safe to continue current regimen regardless of genotype

This acknowledges that some patients with reduced-function genotypes successfully tolerate higher-risk statins, and the absence of symptoms after prolonged exposure suggests individual tolerance.

Clinical Pearls for Implementation

Pearl 1: Dose is as important as the statin choice
A patient with decreased function can often tolerate atorvastatin 10 mg but may develop myalgia on 40 mg. Start low and titrate cautiously in at-risk genotypes.

Pearl 2: Rosuvastatin and pravastatin are the "genetic safety net"
These statins show the most favorable risk profile across all genotypes, making them excellent first-line choices when genetic information is available.

Pearl 3: Consider non-statin lipid-lowering therapy
For poor function patients requiring high-intensity therapy, combination approaches (statin + ezetimibe, statin + PCSK9 inhibitor, or bempedoic acid) may achieve goals while minimizing SAMS risk.

Pearl 4: The "statin rechallenge" takes on new meaning
Armed with genetic information, clinicians can confidently restart statin therapy in previously intolerant patients by selecting genetically appropriate options, improving adherence and outcomes.

The Cost-Benefit Analysis: Is Routine Testing for Every Patient on a Statin Warranted?

The Economic Reality

Pharmacogenetic testing exists at the intersection of clinical benefit and economic feasibility. Multiple cost-effectiveness analyses have examined SLCO1B1 testing, with nuanced conclusions that merit careful consideration.

What the Evidence Shows

A 2021 cost-consequence analysis from the Veterans Affairs system provides sobering insights. In a hypothetical cohort of 10,000 patients, SLCO1B1-informed prescribing averted 109 myalgias and 3 myopathies over one month and reduced statin discontinuations from 109 to 78. However, the testing strategy cost approximately $96 more per patient compared to standard care ($124 vs $28), with the additional cost driven primarily by the genetic testing itself.

The study concluded that standalone SLCO1B1 testing did not achieve cost-effectiveness at conventional thresholds. However, this finding requires contextualization.

The Case for Panel-Based Testing

Multiple analyses converge on an important conclusion: preemptive panel-based pharmacogenetic testing is cost-effective, while reactive single-gene testing is not. A decision-analytic model comparing preemptive multi-gene panels (including CYP2C19-clopidogrel, CYP2C9/VKORC1-warfarin, and SLCO1B1-statins) versus reactive testing showed an incremental cost-effectiveness ratio of $86,227/QALY for preemptive testing—well within acceptable thresholds—while reactive testing exceeded $148,726/QALY.

The economic logic is straightforward: the cost of testing is amortized across multiple drug-gene pairs that the patient may encounter over a lifetime, and results are available at the point of prescribing rather than requiring reanalysis after adverse events occur.

Non-Economic Benefits

Cost-effectiveness analyses capture direct healthcare costs but miss important dimensions:

Patient confidence and adherence: Genetic testing demonstrably improves statin reinitiation rates in previously intolerant patients (55.4% vs 38.0% in one RCT) and improves LDL cholesterol control
Reduced "trial-and-error" prescribing: Genetic guidance reduces unnecessary drug switching and the associated costs, delays, and patient frustration
Shared decision-making: Genetic information empowers patients to make informed choices about their therapy
Avoidance of cardiovascular events: While difficult to quantify in short-term economic models, improved adherence translates to reduced cardiovascular morbidity

Current Recommendations

Who should be tested?

The weight of evidence supports several testing scenarios:

Preemptive panel testing: For patients requiring multiple medications with pharmacogenetic implications (statins, antiplatelet agents, anticoagulants, antidepressants), panel testing is cost-effective and clinically valuable
Reactive testing for statin intolerance: Patients with a history of SAMS should undergo SLCO1B1 testing to guide statin rechallenge, as this scenario has demonstrated clinical utility in improving reinitiation rates
Pre-treatment testing in selected populations: Consider testing before initiating high-dose simvastatin or atorvastatin in patients with additional risk factors for myopathy (elderly, frail, multi-morbid, on interacting medications)

Who should NOT routinely be tested as standalone?

Current evidence does not support routine standalone SLCO1B1 testing for all patients initiating any statin at any dose. The absolute risk reduction in average-risk patients on low-to-moderate dose pravastatin or rosuvastatin is too small to justify the testing cost.

A Teaching Point: The Difference Between Evidence and Guidelines

It's crucial to distinguish clinical utility (does testing improve outcomes?) from cost-effectiveness (is testing worth the cost?). SLCO1B1 testing clearly has clinical utility—it provides actionable information that can guide prescribing. The cost-effectiveness depends heavily on the testing context (standalone vs panel), the population tested (all patients vs enriched populations), and the follow-up duration. As testing costs decline and panel-based approaches become standard, the economic equation continues to shift favorably.

How to Order the Test: A Step-by-Step Guide for the Clinic

Understanding Available Testing Options

SLCO1B1 genotyping is widely available through multiple platforms. Clinicians have several options:

1. Commercial Reference Laboratories

Major providers:

Mayo Clinic Laboratories (Test code: SLC1Q)
ARUP Laboratories (Test code: 2008426)
Quest Diagnostics
LabCorp

Key features:

CLIA-certified, ensuring clinical validity
Typically target the rs4149056 variant (c.521T>C)
Many also include rs2306283 for haplotype determination
Results typically available in 7-14 days
Cost ranges from $100-300 for standalone testing

2. Pharmacogenetic Panels

Comprehensive options:

Mayo Clinic Focused Pharmacogenomics Panel (includes CYPs 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, 4F2, SLCO1B1, VKORC1)
Commercial panels from Genomind, GeneSight, Myriad Neuroscience, Color Genomics
Academic medical center programs (Vanderbilt PREDICT, others)

Advantages:

One-time testing provides lifelong information
More cost-effective per gene tested
Results available for multiple future prescribing decisions
Often integrated with electronic health record clinical decision support

3. Direct-to-Consumer Testing

Available through:

23andMe (includes SLCO1B1 variants in raw data)
Ancestry.com genetic testing
Specific pharmacogenetic companies

Important caveats:

May not be CLIA-certified
Requires interpretation by qualified healthcare provider
May not include all clinically relevant variants
Not currently reimbursable by insurance when used for clinical decision-making

Step-by-Step Ordering Process

Step 1: Determine Testing Indication

Strong indications:

History of statin-associated muscle symptoms
Planned initiation of high-dose simvastatin or atorvastatin
Patient requesting genetic guidance
Part of preemptive pharmacogenetic panel strategy

Consider testing:

Elderly patients (>75 years)
Patients on multiple medications with drug interaction potential
Patients with renal or hepatic impairment
Asian ancestry (different allele frequencies may alter risk-benefit)

Step 2: Obtain Informed Consent

Essential elements to discuss:

Purpose: To identify genetic factors affecting statin pharmacokinetics
Methodology: DNA analysis from blood, saliva, or buccal swab
What will be tested: Specific SLCO1B1 variants
Implications: Results may guide statin selection and dosing
Limitations: Negative test doesn't guarantee absence of SAMS; other factors contribute
Privacy: Genetic information protections under GINA (Genetic Information Nondiscrimination Act)

Note: Some states (e.g., New York) require written informed consent for genetic testing. Verify local regulations.

Step 3: Select Laboratory and Test

For standalone SLCO1B1 testing:

Contact chosen laboratory for test requisition form
Common test names: "SLCO1B1 Genotype," "Statin Pharmacogenetics," "OATP1B1 Genetic Testing"
Specify clinical indication: "Statin therapy guidance" or "History of statin intolerance"

For panel testing:

Select comprehensive pharmacogenetic panel
SLCO1B1 is typically included in cardiovascular or comprehensive panels

Step 4: Collect Sample

Specimen types accepted:

Whole blood (EDTA or ACD anticoagulant): 5-10 mL
Saliva: 2-4 mL using provided collection kit
Buccal swab: Using sterile swab collection kit

Patient preparation:

No fasting required
For saliva: avoid eating, drinking, smoking, or chewing gum 30 minutes before collection
For blood: standard venipuncture procedures

Specimen handling:

Blood: Store at room temperature, ship within 24-48 hours
Saliva/buccal: Follow kit-specific instructions
Use laboratory-provided shipping materials

Step 5: Submit to Laboratory

Required information on requisition:

Patient demographics (name, date of birth, medical record number)
ICD-10 code for billing: Z13.79 (encounter for other screening for genetic and chromosomal anomalies) or Z91.89 (personal history of other specified risk factors)
Clinical indication
Prescribing physician information
Insurance information (if applicable)

Step 6: Interpret Results

Report will typically include:

Genotype at rs4149056: TT, TC, or CC
Genotype at rs2306283 (if tested): AA, AG, or GG
Diplotype/Haplotype: e.g., *1A/*1A, *1A/*5, *5/*5
Predicted Phenotype: Normal, Decreased, or Poor Function
Clinical Recommendations: Often includes CPIC-based guidance

Example result interpretation:

Genotype Result: rs4149056 = TC (heterozygous)
*Diplotype: SLCO1B1 *1A/5
Phenotype: Decreased Function
Interpretation: This patient has moderately reduced OATP1B1 transporter activity and is at increased risk for statin-associated muscle symptoms, particularly with simvastatin or high-dose atorvastatin. Consider prescribing pravastatin, rosuvastatin, or fluvastatin. If using simvastatin, avoid doses >40 mg. Monitor for muscle symptoms.

Step 7: Document and Act

In the medical record:

Document genetic test results in a prominent location
Many EHRs have dedicated pharmacogenetic result fields
Results should be easily accessible for future prescribing decisions

Clinical action:

Prescribe statin according to CPIC guidelines based on phenotype
Counsel patient on genetic findings and implications
Monitor for SAMS as with any statin therapy
Document genotype-guided prescribing rationale

Insurance Coverage and Billing

Current landscape:

Medicare: Coverage varies by MAC (Medicare Administrative Contractor); generally covers with appropriate medical necessity documentation
Private insurance: Inconsistent coverage; many require prior authorization
Out-of-pocket costs: Typically $100-300 for standalone testing, $200-500 for panels
Financial assistance: Many laboratories offer patient assistance programs

Billing codes:

CPT code: 81328 (SLCO1B1 gene analysis, common variant[s])
Diagnosis codes: Z13.79 or Z91.89 as noted above
Documentation of medical necessity improves reimbursement likelihood

Practical Tips for Successful Implementation

Tip 1: Start with a focused population
Begin testing patients with prior statin intolerance rather than universal screening. This builds experience and demonstrates value.

Tip 2: Integrate with clinical decision support
Work with your EHR vendor or IT team to create alerts that display genetic results when prescribing statins.

Tip 3: Educate patients proactively
Provide written materials explaining pharmacogenetic testing and its implications for their care.

Tip 4: Create a workflow
Designate team members responsible for ordering, tracking results, and documenting findings. Consistency improves implementation success.

Tip 5: Consider panel testing from the start
If your patient population uses multiple medications with pharmacogenetic implications (cardiovascular patients often do), panel testing provides better value and comprehensiveness.

Oysters and Pearls: Clinical Wisdom for the Practitioner

Pearl 1: The "Nocebo Effect" in Statin Intolerance

Studies show that many patients attributed muscle symptoms to statins in blinded trials actually had similar rates on placebo. When you can reassure a genetically low-risk patient that their biology supports safe statin use, you may break the cycle of anticipatory anxiety that perpetuates symptoms.

Pearl 2: Genetic Risk is Dose-Dependent

A patient with *1A/*5 genotype may tolerate atorvastatin 10 mg perfectly well but develop myalgias on 40 mg. Genetic information doesn't mandate avoiding a statin entirely—it guides dose selection.

Pearl 3: Drug Interactions Multiply Genetic Risk

A decreased function genotype combined with CYP3A4 inhibitors (clarithromycin, diltiazem, amiodarone) creates particularly high risk for simvastatin or atorvastatin. Consider pravastatin or rosuvastatin in these scenarios regardless of genetic results.

Pearl 4: Ethnicity Matters

Asian patients show different allele frequencies and may have enhanced statin sensitivity beyond SLCO1B1 genetics. FDA labeling acknowledges this with lower recommended starting doses of rosuvastatin in Asian populations.

Pearl 5: The Rechallenge Opportunity

Genetic testing transforms the statin rechallenge from guesswork into precision. Patients previously intolerant to simvastatin who learn they have normal SLCO1B1 function can often successfully restart with a different statin, guided by knowledge that genetics wasn't their problem.

Oyster 1: When Genetic Testing Misleads

A patient with normal function genotype can still develop SAMS due to other mechanisms (mitochondrial factors, vitamin D deficiency, hypothyroidism, inherent muscle disease). Negative genetic testing doesn't eliminate the need for clinical vigilance.

Oyster 2: The Genetic Attribution Trap

Not every muscle symptom in a poor function patient is genetically caused. Temporal relationship matters—symptoms appearing after years of stable therapy are less likely to be pharmacogenetic and more likely related to other factors.

Oyster 3: Cost vs. Value in Resource-Limited Settings

In settings where genetic testing is prohibitively expensive or unavailable, empiric use of pravastatin or rosuvastatin achieves similar safety outcomes for most patients without testing. Genetics adds precision but isn't mandatory for safe prescribing.

Future Directions and Evolving Knowledge

Beyond SLCO1B1: Other Genetic Factors

Emerging research identifies additional genes influencing statin response:

ABCG2: Affects rosuvastatin pharmacokinetics
CYP2C9: Influences fluvastatin metabolism
GATM, CKM: Muscular factors affecting myopathy risk independent of pharmacokinetics
Gene risk scores combining multiple variants may improve risk prediction

Preemptive vs. Reactive Testing

The field is moving toward preemptive panel-based testing, where multiple pharmacogenes are tested once and results remain available in the electronic health record for all future prescribing decisions. This approach is more cost-effective and clinically practical than reactive single-gene testing after adverse events occur.

Implementation Science

Major academic medical centers (Vanderbilt, Mayo Clinic, others) have demonstrated feasibility of large-scale pharmacogenetic implementation with clinical decision support. The challenge remains dissemination to community practice settings, where most prescribing occurs.

Regulatory Evolution

The FDA has expanded drug labeling to include pharmacogenetic information for multiple statins. Future updates may include more explicit dosing recommendations based on SLCO1B1 genotype, moving from "informational" to "actionable" labeling categories.

Conclusion: From Genes to Bedside

SLCO1B1 pharmacogenetics exemplifies precision medicine at its finest: a well-characterized biological mechanism, robust genetic associations, actionable clinical recommendations, and measurable patient benefits. While not every patient requires genetic testing, the availability of this tool empowers clinicians to transform statin intolerance from a frustrating clinical problem into a solvable genetic puzzle.

For the postgraduate learner, SLCO1B1 serves as a model for understanding how genetic variation in drug transporters affects pharmacokinetics, how to interpret pharmacogenetic test results, and how to apply guidelines to individualize therapy. As pharmacogenomics becomes increasingly integrated into routine practice, these principles will extend beyond statins to encompass growing numbers of medications and gene-drug pairs.

The statin-intolerant patient need no longer abandon therapy in frustration. Armed with genetic insights, we can prescribe the right statin, at the right dose, to the right patient—guided by their individual biology rather than by trial and error. This is pharmacogenetics in action, and this is the future of medicine.

Key References

Link E, Parish S, Armitage J, et al. SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med. 2008;359(8):789-799.
Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther. 2022;111(5):1007-1021.
Donnelly LA, Doney ASF, Tavendale R, et al. Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study. Clin Pharmacol Ther. 2011;89(2):210-216.
Lönnberg KI, Tornio A, Hirvensalo P, et al. Real-world pharmacogenetics of statin intolerance: effects of SLCO1B1, ABCG2, and CYP2C9 variants. Pharmacogenet Genomics. 2023;33(7):153-160.
Niemi M, Pasanen MK, Neuvonen PJ. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011;63(1):157-181.
Peyser B, Perry EP, Singh K, et al. Effects of delivering SLCO1B1 pharmacogenetic information in randomized trial and observational settings. Circ Genom Precis Med. 2018;11(9):e002228.
Chanfreau-Coffinier C, Hull LE, Lynch JA, et al. A cost–consequence analysis of preemptive SLCO1B1 testing for statin myopathy risk compared to usual care. J Pers Med. 2021;11(11):1123.
Zhu Y, Swanson KM, Rojas RL, et al. Systematic review of the cost-effectiveness of pharmacogenetic-guided treatment for cardiovascular diseases. Genet Med. 2020;22(3):572-583.

This review represents current evidence as of 2024-2025 and should be supplemented with the most recent CPIC guidelines and institutional protocols when implementing pharmacogenetic testing in clinical practice.