Welcome to ACC’s Statin Intolerance Tool

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Click the Terms tab at the bottom of the app before using the LDL-C Lowering Therapy, Hypertriglyceridemia, or Statin Intolerance tools in the Lipid Manager (“the Product”) to read the full Terms of Service and License Agreement (the “Agreement”) which governs the use of the Product. The Agreement includes, among other detailed terms and conditions, certain disclaimers of warranties by the American College of Cardiology Foundation (“ACCF”), terms governing the use of AHA’s PREVENT™ calculator, and requires the user to agree to release ACCF from any and all liability arising in connection with your use of the Product. By using the Product, you accept and agree to be bound by all of the terms and conditions set forth in the Agreement, including such disclaimers and releases. If you do not accept the terms and conditions of the Agreement, you may not proceed to use the Product. The Agreement is subject to change from time to time, and your continued use of the Product constitutes your acceptance of and agreement to be bound by any revised terms of the Agreement.

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This tool should be used by clinicians to assess, treat, and manage patients with possible statin intolerance.

Although muscle symptoms may occur, true statin intolerance is uncommon. Given the benefits of statins in ASCVD risk reduction, clinicians should partner with the patient to gain a thorough symptom history and determine if he or she is truly statin intolerant. Walk through the steps of treating and managing a patient who reports muscle symptoms, including cycles of statin discontinuation and rechallenge to identify a tolerated statin and dose.

Clear Data

Current Statin and Drug Interactions

Consider a 5 mg starting dose for Rosuvastatin in Asian population. Simvastatin – Initiation at 80mg daily or increase of up to 80mg daily may cause harm (III, A). Selected dose is not included in the guideline.
Yes No
(e.g., fenofibrates, strong CYP3A4 inhibitors)
Evaluate Skip
Yes, Edit None Selected

Muscle Symptoms Type, Severity, and Secondary Causes

Symptom Type

Symptom Area

 Severe/Intolerable  Mild/Moderate/Tolerable
Or use worksheet to assess severity.

Rhabdomyolysis Assessment (if Severe/Intolerable)

For patients who indicate Severe or Intolerable Muscle Symptom severity.

No Yes Don't Know
CK is elevated. Check for Rhabdomyolysis by: Evaluating CK Level, Evaluating Creatinine, Performing Urinalysis for Myoglobin. Fever, discolored urine, and/ or marked weakness in the patient signal the need for emergency attention. Check for Rhabdomyolysis by: Evaluating CK Level, Evaluating Creatinine, Performing Urinalysis for Myoglobin. Fever, discolored urine, and/ or marked weakness in the patient signal the need for emergency attention.
More information about CK Levels.

Symptom Timing

When did muscle symptoms begin, compared to starting the current statin treatment?

Click here to see a list of all recommended labs to assess Statin Intolerance.

Secondary Considerations

  1. Determine if patient has done anything recently outside their normal routine that may cause muscle pain.
    (e.g., moved furniture, started a new medication, changed their eating habits)
  2. Use the worksheets below to determine any medical history that may also be contributing to symptoms.
Evaluate Skip
Yes, Edit None Selected
Evaluate Skip
Yes, Edit None Selected

Factors that increase risk for statin symptoms (e.g., substance abuse, comorbidities)

Select all that apply

Non-statin causes for muscle symptoms (e.g., primary muscle diseases, rheumatological disorders)

Select all that apply
Results   Results 

Likelihood of Statin-Attributed Muscle Symptoms with Current Prescription

Statin: Dose: | Frequency:


Statin-Attributed Muscle Symptoms Statin-Attributed Muscle Symptoms
Muscle Symptoms Result Possible Possible Unlikely Unlikely
 
    Result Possible Possible Unlikely Unlikely
 
    Result Possible Possible Unlikely Unlikely

Next Steps


  1. Verify statin-attributed muscle symptoms with side effects on ≥2 statins, 1 at lowest FDA-approved dose.
  2. Have benefit-risk discussion, evaluate secondary causes of muscle symptoms, and assess muscle strength. (1)
  3. If severe myalgias or muscle weakness, measure creatine kinase. (1)
  4. Consider evidence-based non-statin treatments for adult patients with statin-attributed muscle symptoms to lower LDL-C and reduce ASCVD risk.

Click Follow-Up to see next steps for continuing statin therapy, or click the Drug Compare tab for help in selecting a different statin.

Evidence-based non-statin treatments for adult patients with statin-attributed muscle symptoms

Indicate most relevant patient population subgroup:

Calculate PREVENT™-ASCVD 10-year Risk Estimate (for patients without clinical ASCVD)

CALCULATED 10-YEAR RISK SCORE:
Management of Statin-Attributed Muscle Symptoms Advice:

For patients without clinical ASCVD and with PREVENT-ASCVD 10-year risk <10%, a goal of LDL-C <100 mg/dL and non-HDL-C <130 mg/dL may be considered. If this goal is not achieved, addition ezetimibe and/or bempedoic acid may be reasonable. If initiation of nonstatin therapy is uncertain, optional use of CAC scoring may be considered.

Full Text:
  • In adults without a history of clinical ASCVD who experience statin-attributed muscle symptoms on the recommended intensity of statin therapy (secondary causes excluded) and are at borderline or intermediate ASCVD risk based on a PREVENT-ASCVD equation of 3 to <10%, the addition of ezetimibe and/or bempedoic acid may be reasonable to lower LDL-C to <100 mg/dL (2.6 mmol/L) and non-HDL-C to <130 mg/dL (3.4 mmol/L) and reduce ASCVD risk. (2b, B-NR)
  • In adults without a history of clinical ASCVD who experience statin-attributed muscle symptoms on the recommended intensity of statin therapy (secondary causes excluded) and are at borderline to intermediate ASCVD risk based on a PREVENT-ASCVD equation of 3 to <10%, and in whom the decision to treat with ezetimibe and/or bempedoic acid is uncertain, coronary calcium scoring may be reasonable to aid in ASCVD risk stratification to inform decision making about add-on therapy to reduce ASCVD risk. (2b, B-R)
Management of Statin-Attributed Muscle Symptoms Advice:

For patients without clinical ASCVD, and with either PREVENT-ASCVD 10-year risk ≥10%, CAC ≥300 AU, or diabetes, a goal of LDL-C <70 mg/dL and non-HDL-C <100 mg/dL is recommended (with an optional apoB goal of <70 mg/dL) . If this goal is not achieved, addition of bempedoic acid and/or ezetimibe is recommended. If goal is still not achieved, addition of PCSK9 mAb is reasonable.

Full Text:
  • In adults without a history of clinical ASCVD who experience statin-attributed muscle symptoms on the recommended intensity of statin therapy (secondary causes excluded) and are at high ASCVD risk based on a PREVENT-ASCVD equation of ≥10% or a CAC score ≥300 AU, or women >65 years of age or men >60 years of age with diabetes, the addition of bempedoic acid and/or ezetimibe is/are indicated to lower LDL-C to <70 mg/dL (1.8 mmol/L) and non-HDL-C <100 mg/dL (2.6 mmol/L) and to reduce ASCVD risk. (1, B-R)
  • In adults without a history of clinical ASCVD who experience statin-attributed muscle symptoms on the recommended intensity of statin therapy (secondary causes excluded) and are at high ASCVD risk based on a PREVENT-ASCVD equation of ≥10% or CAC score ≥300 AU or diabetes and are unable to achieve recommended treatment goals, the addition of a PCSK9 mAb is reasonable to lower LDL-C. (2a, B-R)
Management of Statin-Attributed Muscle Symptoms Advice:

For patients with clinical ASCVD, addition of reduced-dose statin (if tolerated), bempedoic acid, ezetimibe, and/or PCSK9 mAb is recommended if goal is not achieved. Optionally, measurement of apoB is reasonable to guide decisions. For patients unable to tolerate, obtain, or adhere to PCSK9 mAb therapy, addition of inclisiran* to lower LDL-C is reasonable, otherwise monitor adherence and response to therapy.
*Cardiovascular outcomes for inclisiran pending results of ongoing RCTs.

Full Text:
  • In adults with clinical ASCVD who experience statin-attributed muscle symptoms on the recommended intensity of statin therapy (secondary causes excluded) and are unable to achieve recommended treatment goals, use of a reduced statin dose (if tolerable) and the addition of bempedoic acid, ezetimibe, or a PCSK9 mAb, alone or in combination, are recommended to lower LDL-C and reduce ASCVD risk. (1, B-R)
  • In adults on LLT, particularly those with ASCVD, CKM syndrome, type 2 diabetes, and/or elevated TG, measurement of apoB is reasonable to guide decisions regarding further therapeutic intensification once LDL-C and/or non-HDL-C goals are achieved. (2a, B-NR)
  • In adults with clinical ASCVD who experience statin-attributed muscles symptoms (secondary causes excluded) and are unable to achieve recommended treatment goals on bempedoic acid with or without ezetimibe, it is reasonable to add inclisiran in those unable to tolerate or obtain evolocumab or alirocumab or who have a strong preference for less frequent dosing to achieve an LDL-C goal <55 mg/dL (1.4 mmol/L) and non-HDL-C <85 mg/dL (2.2 mmol/L). (2a, B-NR)
  • In adults with dyslipidemia, an individualized clinician-patient discussion prior to initiating lipid-lowering medication is recommended to review the benefits and risks of pharmacotherapy to promote patient engagement and medication adherence. (1, A)

For more information on evidence-based non-statin therapies for lowering LDL-C, see ACC's LDL-C Lowering Therapy app.

The PREVENT™ equations were developed by select members of the American Heart Association Cardiovascular-Kidney-Metabolic Scientific Advisory Group. The risk equations were derived and validated in a large, diverse sample of over 6 million individuals.[1],[2]

[1] Khan SS, Matsushita K, Sang Y, et al. Development and Validation of the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENTTM) Equations. Circulation 2023. DOI: 10.1161/CIRCULATIONAHA.123.067626.

[2] Khan SS, Coresh J, Pencina MJ, et al. Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association. Circulation 2023;148(24):1982-2004. DOI: 10.1161/CIR.0000000000001191.

The information derived from the use of PREVENT™ is based on PREVENT™ 1.0.0. Updates and future adaptations of PREVENT™ may yield different results and conclusions.

The American College of Cardiology Foundation is an independent entity and is not affiliated with, endorsed by, sponsored by, or approved by American Heart Association (“AHA”). Use of the PREVENTTM risk model and related materials is pursuant to a license from AHA and does not imply any partnership or association.

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Class:
Mechanism of Action
Medications and Dosing
Medications Typical Dose Range Dosing Frequency
Guideline Comments†
Common Side Effects
Contraindications‖
Comments
FDA-approved indication(s)§

Drug information and Interactions

    Secondary Medication Contraindicated

    Secondary Medication Dosage Warning

See below for full drug warnings.

Dose info
‡Initiation at 80mg daily or increase of up to 80mg daily may cause harm.
Legend - Dosing: Boldface
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Dose Legend

Boldface type indicates specific statins and doses that were evaluated in RCTs (16–17,18–46,47–48,49) included in CQ1, CQ2, and the Cholesterol Treatment Trialists 2010 meta-analysis included in CQ3 (20). All of these RCTs demonstrated a reduction in major cardiovascular events. Italic type indicates statins and doses that are approved by the FDA but have not been tested in the RCTs reviewed. BID indicates twice daily; CQ, critical question; FDA, Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; and RCTs, randomized controlled trials

  • * Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biological basis for a less-than-average response.
  • † Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study (47).
  • ‡ Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the increased risk of myopathy, including rhabdomyolysis.
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Statin Characteristics

Statin’s Interactions with Drugs You Selected The tables below only represents major drug interactions and are not an exhaustive list. Some drugs may fall under multiple categories. The tables are compiled only from the following sources and may not represent all possible interactions: † Prescribing Information - § Expert Opinion - ‡ FDA Recommendation - * ACC/AHA Guideline Recommendation

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Secondary Drugs You Selected

Interactions with Secondary Drugs
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  • † Prescribing Information
  • § Expert Opinion
  • ‡ FDA Recommendation
  • * ACC/AHA Guideline Recommendation
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Follow-up process

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Select where you are in the follow-up process

Back to Follow-Up Reasons

Current Follow-Up

Labs have been returned.
Has a non-statin cause for statin-attributed muscle symptoms been identified?
Yes No

Recommendation

Next Steps
  • Treat identified cause of statin-attributed muscle symptoms.
  • If CK is elevated above 10x ULN, check for rhabdomyolysis by evaluating creatinine and performing urinalysis for myoglobinuria.
Continuing Statin Therapy
  • If no rhabdomyolysis, continue statin therapy at original dose once issue has been resolved.
  • Or, you may consider an alternate statin if patient prefers.
Next Follow-Up: Patient was taken off the original statin

Recommendation

Next Steps
  • If CK is elevated above 10x ULN, check for rhabdomyolysis by evaluating creatinine and performing urinalysis for myoglobinuria.
Continuing Statin Therapy
  • If no rhabdomyolysis:
    • If patient is still taking a statin, consider temporarily suspending the statin and follow up to see if symptoms resolve.
    • If patient was already taken off original statin, follow up to see if symptoms have resolved.
  • Use the other steps in the Follow-Up section of this app for further guidance.
Next Follow-Up: Patient was taken off the original statin

Current Follow-Up

Patient was taken off original statin
Did statin-attributed muscle symptoms resolve after statin discontinuation?
Yes No

Recommendation

Next Steps
  • Establish statin adverse effects causation by restarting patient on a same or lower dose of the statin taken at time of muscle complaint.
  • Or, if patient prefers, consider starting a low dose of a different statin. If low dose is tolerated, gradually increase the dose as tolerated.
Next Follow-Up
  • Follow up with patient to assess whether statin-attributed muscle symptoms return.
Things to Consider
  • Intolerance to one or more statins does not necessarily indicate intolerance to all statins.
  • Consider characteristics of each statin such as metabolism, lipophilicity, drug interactions, etc. when prescribing.
  • Use this app’s Drug Comparison Calculator for help.
Clinician-Patient Discussion
  • When considering alternative statins and/or doses, it may be helpful to clarify how statins differ from one another and that those characteristics may cause another drug to work better for a particular patient.
  • Use the following points to discuss patient’s preferences and ability to comply with treatment.
    • Potential ASCVD risk-reduction benefits
    • Potential adverse effects and drug–drug interactions
    • Living a heart-healthy lifestyle
    • Managing other risk factors
Next Follow-Up: Patient was rechallenged with the original statin

Recommendation

Next Steps
  • Investigate any possible non-statin causes for symptoms. Use this app’s “Evaluate” tab for help.
  • Do not restart statin until symptoms resolve.
Things to Consider
  • In some cases, symptoms can take up to two months to resolve.
Next Follow-Up: Patient was rechallenged with the original statin

Current Follow-Up

Patient has been rechallenged with original statin
Did statin-attributed muscle symptoms return after rechallenge?
Yes No

Recommendation

Next Steps
  • Stop original statin.
  • Wait for statin-attributed muscle symptoms to resolve again.
Continuing Statin Therapy
  • Once symptoms have resolved, start a low dose of a different statin.
  • If low dose of a statin is tolerated, gradually increase the dose as tolerated.
  • Reevaluate if statin-attributed muscle symptoms return.
Things to Consider
  • Intolerance to one or more statins does not necessarily indicate intolerance to all statins.
  • Consider characteristics of each statin such as metabolism, lipophilicity, drug interactions, etc. when prescribing.
  • Use this app’s Drug Comparison Calculator for help.
Clinician-Patient Discussion
  • When considering alternate statin types and/or doses, it may be helpful to clarify how statins differ from one another and that those characteristics may cause another drug to work better for a particular patient.
  • Use the following points to discuss a patient’s preference for and ability to follow treatment.
    • Potential ASCVD risk-reduction benefits
    • Potential adverse effects, and drug–drug interactions
    • Living a heart-healthy lifestyle
    • Managing other risk factors
Next Follow-Up:Considering starting patient on alternative statin

Recommendation

Next Steps
  • Continue with current statin prescription.
Next Follow-Up:Considering starting patient on alternative statin

Current Follow-Up

Considering starting patient on alternative statin

Considering alternative statin because:

  • Statin-attributed muscle symptoms occurred on a previous statin and no non-statin cause for symptoms has been identified, and/or
  • Clinician-Patient discussion determined preference for trying different statin.
Does patient currently have statin-attributed muscle symptoms?
Yes No

Recommendation

Wait until symptoms resolve before taking next steps.
Next Steps
  • Start a low dose of a different statin.
  • If low dose of a statin is tolerated, gradually increase the dose as tolerated.
  • Reevaluate if statin-attributed muscle symptoms return.
Things to Consider
  • Intolerance to one or more statins does not necessarily indicate intolerance to all statins.
  • Consider characteristics of each statin such as metabolism, lipophilicity, drug interactions, etc. when prescribing. Use this app’s Drug Comparison Calculator for help.
Clinician-Patient Discussion
  • When considering alternate statin types and/or doses, it may be helpful to clarify how statins differ from one another and that those characteristics may cause another drug to work better for a particular patient.
  • Use the following points to discuss a patient’s preference for and ability to follow treatment.
    • Potential ASCVD risk-reduction benefits
    • Potential adverse effects, and drug–interactions
    • Living a heart-healthy lifestyle
    • Managing other risk factors
Next Follow-Up: Statin-attributed muscle symptoms returned on alternative statin  

Recommendation

Next Steps
  • Start a low dose of a different statin.
  • If low dose of a statin is tolerated, gradually increase the dose as tolerated.
  • Reevaluate if statin-attributed muscle symptoms return.
Consider
  • Intolerance to one or more statins does not necessarily indicate intolerance to all statins.
  • Consider characteristics of each statin such as metabolism, lipophilicity, drug interactions, etc. when prescribing. Use this app’s Drug Comparison Calculator for help.
Clinician-Patient Discussion
  • When considering alternate statin types and/or doses, it may be helpful to clarify how statins differ from one another and that those characteristics may cause another drug to work better for a particular patient.
  • Use the following points to discuss a patient’s preference for and ability to follow treatment.
    • Potential ASCVD risk-reduction benefits
    • Potential adverse effects, and drug–drug interactions
    • Living a heart-healthy lifestyle
    • Managing other risk factors
Next Follow-Up: Statin-attributed muscle symptoms returned on alternative statin  

Statin-attributed muscle symptoms returned after starting an alternate statin.

Current Follow-Up
Were any non-statin causes for statin-attributed muscle symptoms identified?
Yes No

Recommendation

Next Steps
  • Treat identified cause of statin-attributed muscle symptoms.
  • Continue current statin therapy prescription once issue has been resolved.
  • Or, you may consider an alternate statin type or dose if patient prefers.

Recommendation

Next Steps
  • Consider the patient’s ASCVD risk and cardiovascular health history, benefits of statin therapy and risk of removal, and patient preferences.
  • Consider evidence-based non-statin treatments for adult patients with statin-attributed muscle symptoms.
    • See Results after completing an Evaluation for Statin Intolerance for more information on non-statin lipid-lowering therapy.
Continuing Statin Therapy
  • Proceed with one of the following as appropriate:
    • A. Continue with current statin prescription
    • B. Try an alternative statin:
      • Discontinue current statin. Wait for symptoms to resolve.
      • Try patient on a low dose of an alternative statin.
      • If low dose is tolerated, gradually increase dose as tolerated.
    • If statin-attributed muscle symptoms have occurred on two or more statins, and symptoms outweigh risk and benefit, you may consider discussing alternate treatment methods with the patient.
Things to Consider
  • Intolerance to one or more statins does not necessarily indicate intolerance to all statins.
  • In addition to a variety of non-statin causes, onset of muscle symptoms in a patient who has previously tolerated statins can be caused by any number of changes in their clinical status. Continue to consider secondary causes.
  • Consider characteristics of each statin such as metabolism, lipophilicity, drug interactions, etc. when prescribing. Use this app’s Drug Comparison Calculator for help.

Statin Drug Comparison

When developing a dosing strategy

  1. Compare different statin characteristics, especially lipophilicity and metabolism.
  2. Consider patient characteristics (e.g. age, family history of statin intolerance, renal function, liver disease).
Secondary Drug Selector Skip

Select Statin

    Secondary Medication Contraindicated

    Secondary Medication Dosage Warning

See below for full drug warnings.

Dose Info
‡Initiation at 80mg daily or increase of up to 80mg daily may cause harm.
Legend - Dosing: Boldface
close

Dose Legend

Boldface type indicates specific statins and doses that were evaluated in RCTs (16–17,18–46,47–48,49) included in CQ1, CQ2, and the Cholesterol Treatment Trialists 2010 meta-analysis included in CQ3 (20). All of these RCTs demonstrated a reduction in major cardiovascular events. Italic type indicates statins and doses that are approved by the FDA but have not been tested in the RCTs reviewed. BID indicates twice daily; CQ, critical question; FDA, Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; and RCTs, randomized controlled trials

  • * Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biological basis for a less-than-average response.
  • † Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study (47).
  • ‡ Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the increased risk of myopathy, including rhabdomyolysis.
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Statin Characteristics

Secondary Drug Warnings The tables below only represents major drug interactions and are not an exhaustive list. Some drugs may fall under multiple categories. The tables are compiled only from the following sources and may not represent all possible interactions: † Prescribing Information - § Expert Opinion - ‡ FDA Recommendation - * ACC/AHA Guideline Recommendation

You have no Secondary Drugs Selected.

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Statin’s Interactions with Drugs You Have Selected
info her
(selected)
info her

Statin’s Interactions with All Listed Secondary Drugs
info her
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  • † Prescribing Information
  • § Expert Opinion
  • ‡ FDA Recommendation
  • * ACC/AHA Guideline Recommendation
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Selected Secondary Drugs ()

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Select Statin Characteristic
Atorvastatin (Lipitor) hello
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Half life / Metabolic Pathway / Lipophcilitiy

++ CYP3A4 inhibitors may increase the plasma concentration of these statins, increasing the risk of adverse reactions such myopathy and/or rhabdomyolysis. (New Zealand reference/FDA) Use caution with inhibitors (e.g., verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, grapefruit juice) and inducers (e.g., rifampin, phenobarbital, phenytoin). (ACC AF guideline refernece)

http://www.medsafe.govt.nz/profs/PUArticles/March2014StatinsAndCYPInteractions.htm

http://www.fda.gov/Drugs/DrugSafety/ucm293877.htm

**http://www.pharmacologyweekly.com/articles/statin-administration-evening-night-bedtime

II Studies show that the most hydrophilic statins were least likely to cause myalgia, whereas the most lipophilic ones were most likely to be associated with muscular adverse effects (4).
http://care.diabetesjournals.org/content/36/Supplement_2/S325.full

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Low Intensity
Atorvastatin (Lipitor)

Moderate Intensity
Atorvastatin (Lipitor)

High Intensity
Atorvastatin (Lipitor)
Legend - Dosing: Boldface
close

Dose Legend

Boldface type indicates specific statins and doses that were evaluated in RCTs (16–17,18–46,47–48,49) included in CQ1, CQ2, and the Cholesterol Treatment Trialists 2010 meta-analysis included in CQ3 (20). All of these RCTs demonstrated a reduction in major cardiovascular events. Italic type indicates statins and doses that are approved by the FDA but have not been tested in the RCTs reviewed. BID indicates twice daily; CQ, critical question; FDA, Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; and RCTs, randomized controlled trials

  • * Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biological basis for a less-than-average response.
  • † Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study (47).
  • ‡ Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the increased risk of myopathy, including rhabdomyolysis.
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Resources

Resources

Back to Guidlines & Resources

Statin Safety Recommendations

Statin Selection

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To maximize the safety of statins, selection of the appropriate statin and dose in men and nonpregnant/nonnursing women should be based on patient characteristics, level of ASCVD risk, and potential for adverse effects. Moderate-intensity statin therapy should be used in individuals in whom high-intensity statin therapy would otherwise be recommended when characteristics predisposing them to statin associated adverse effects are present.

Characteristics predisposing individuals to statin adverse effects include, but are not limited to:

  • Multiple or serious comorbidities, including impaired renal or hepatic function.
  • History of previous statin intolerance or muscle disorders.
  • Unexplained ALT elevations >3 times ULN.
  • Patient characteristics or concomitant use of drugs affecting statin metabolism.
  • ≥ 75 years of age.

Additional characteristics that may modify the decision to use higher statin intensities may include, but are not limited to:

  • History of hemorrhagic stroke.
  • Asian ancestry.
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Statin Dosage

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  • Decreasing the statin dose may be considered when 2 consecutive values of LDL-C levels are <40 mg/dL.
  • It may be harmful to initiate simvastatin at 80 mg daily or increase the dose of simvastatin to 80 mg daily. (III A)
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Creatine Kinase (CK)

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  • CK should not be routinely measured in individuals receiving statin therapy. (III A)
  • Baseline measurement of CK is reasonable for individuals believed to be at increased risk for adverse muscle events based on a personal or family history of statin intolerance or muscle disease, clinical presentation, or concomitant drug therapy that might increase the risk for myopathy.
  • During statin therapy, it is reasonable to measure CK in individuals with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue. (II C)
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Muscle Symptoms

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It is reasonable to evaluate and treat muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue, in statin-treated patients according to the following management algorithm: (IIa B)

  • To avoid unnecessary discontinuation of statins, obtain a history of prior or current muscle symptoms to establish a baseline before initiating statin therapy.
  • If unexplained severe muscle symptoms or fatigue develop during statin therapy, promptly discontinue the statin and address the possibility of rhabdomyolysis by evaluating CK, creatinine, and a urinalysis for myoglobinuria.
  • If mild to moderate muscle symptoms develop during statin therapy:
    • Discontinue the statin until the symptoms can be evaluated.
    • Evaluate the patient for other conditions that might increase the risk for muscle symptoms (e.g., hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases).
    • If muscle symptoms resolve, and if no contraindication exists, give the patient the original or a lower dose of the same statin to establish a causal relationship between the muscle symptoms and statin therapy.
    • If a causal relationship exists, discontinue the original statin. Once muscle symptoms resolve, use a low dose of a different statin.
    • Once a low dose of a statin is tolerated, gradually increase the dose as tolerated.
    • If, after 2 months without statin treatment, muscle symptoms or elevated CK levels do not resolve completely, consider other causes of muscle symptoms listed above.
    • If persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume statin therapy at the original dose.
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Hepatic Function

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  • Baseline measurement of hepatic transaminase levels (ALT) should be performed before initiating statin therapy.
  • During statin therapy, it is reasonable to measure hepatic function if symptoms suggesting hepatotoxicity arise (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine or yellowing of the skin or sclera).
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Diabetes

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Individuals receiving statin therapy should be evaluated for new-onset diabetes mellitus according to the current diabetes screening guidelines. Those who develop diabetes mellitus during statin therapy should be encouraged to adhere to a heart healthy dietary pattern, engage in physical activity, achieve and maintain a healthy body weight, cease tobacco use, and continue statin therapy to reduce their risk of ASCVD events.

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Age and Drug Regimen Consideration

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For individuals taking any dose of statins, it is reasonable to use caution in individuals >75 years of age, as well as in individuals that are taking concomitant medications that alter drug metabolism, taking multiple drugs, or taking drugs for conditions that require complex medication regimens (e.g., those who have undergone solid organ transplantation or are receiving treatment for HIV). A review of the manufacturer's prescribing information may be useful before initiating any cholesterol-lowering drug.

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Cognitive Impairment

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For individuals presenting with a confusional state or memory impairment while on statin therapy, it may be reasonable to evaluate the patient for nonstatin causes, such as exposure to other drugs, as well as for systemic and neuropsychiatric causes, in addition to the possibility of adverse effects associated with statin drug therapy.

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Groups that Benefit from Statin Therapy

Secondary Prevention: Clinical ASCVD

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Clinical ASCVD includes acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin. High-intensity statin therapy should be initiated or continued as first-line therapy in women and men ≤75 years of age who have clinical ASCVD, unless contraindicated. (I A)

In individuals with clinical ASCVD in whom high-intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated. (I A)

In individuals with clinical ASCVD >75 years of age, it is reasonable to evaluate the potential for ASCVD risk-reduction benefits and for adverse effects, drug-drug interactions and to consider patient preferences, when initiating a moderate- or high-intensity statin. It is reasonable to continue statin therapy in those who are tolerating it. (IIa B)

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Primary Prevention: LDL-C ≥190mg/dL

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Individuals with LDL-C ≥190 mg/dL or triglycerides ≥500 mg/dL should be evaluated for secondary causes of hyperlipidemia.

Adults ≥21 years of age with primary LDL-C ≥190 mg/dL should be treated with high-intensity statin therapy unless contraindicated. For individuals unable to tolerate high-intensity statin therapy, use the maximum tolerated statin intensity.

For individuals ≥21 years of age with an untreated primary LDL-C ≥190 mg/dL, it is reasonable to intensify statin therapy to achieve at least a 50% LDL-C reduction. (IIa B)

For individuals ≥21 years of age with an untreated primary LDL-C ≥190 mg/dL, after the maximum intensity of statin therapy has been achieved, addition of a nonstatin drug may be considered to further lower LDL-C. Evaluate the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and consider patient preferences.

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Primary Prevention: Diabetes and aged 40 to 75 years with LDL-C between 70-189 mg/dL

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Moderate-intensity statin therapy should be initiated or continued for adults 40 to 75 years of age with diabetes mellitus. (I A)

High-intensity statin therapy is reasonable for adults 40 to 75 years of age with diabetes mellitus with a ≥7.5% estimated 10-year ASCVD risk unless contraindicated. (IIa B)

In adults with diabetes mellitus, who are <40 or >75 years of age, it is reasonable to evaluate the potential for ASCVD benefits and for adverse effects, for drug-drug interactions, and to consider patient preferences when deciding to initiate, continue, or intensify statin therapy. (IIa C)

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Primary Prevention: NO diabetes and estimated 10-year ASCVD risk of >7.5% who are between 40 to 75 years of age with LDL-C between 70-189 mg/dL

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The Pooled Cohort Equations should be used to estimate 10-year ASCVD risk for individuals with LDL-C 70 to 189 mg/dL without clinical ASCVD to guide initiation of statin therapy for the primary prevention of ASCVD.

Before initiating statin therapy for the primary prevention of ASCVD in adults with LDL-C 70 - 189 mg/dL without clinical ASCVD or diabetes it is reasonable for clinicians and patients to engage in a discussion which considers the potential for ASCVD risk reduction benefits and for adverse effects, for drug-drug interactions, and patient preferences for treatment.

Adults 40 to 75 years of age with LDL-C 70 to 189 mg/dL, without clinical ASCVD or diabetes and an estimated 10-year ASCVD risk ≥7.5% should be treated with moderate- to high-intensity statin therapy. (I A)

It is reasonable to offer treatment with a moderate-intensity statin to adults 40 to 75 years of age, with LDL-C 70 to 189 mg/dL, without clinical ASCVD or diabetes and an estimated 10-year ASCVD risk of 5% to <7.5%. (IIa B)

In adults with LDL-C <190 mg/dL who are not otherwise identified in a statin benefit group, or for whom after quantitative risk assessment a risk-based treatment decision is uncertain, additional factors may be considered to inform treatment decision making. In these individuals, statin therapy for primary prevention may be considered after evaluating the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and discussion of patient preferences.

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Additional Factors

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These factors may include:
Statin benefit may be less clear in other groups; additional factors may be considered to inform treatment decision making.

  1. 5 to <7.5% 10-year ASCVD risk
  2. Primary LDL-C ≥160 mg/dL or other evidence of genetic hyperlipidemias
  3. Family history of premature ASCVD
  4. High sensitivity C-reactive protein ≥2 mg/L
  5. Coronary artery calcium score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity
  6. Ankle-brachial index <0.9
  7. Lifetime risk of ASCVD
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Recommendations for Initiation of Statin Therapy

Statin Therapy Flowcharts

This flow diagram is intended to serve as an easy reference guide summarizing recommendations for ASCVD risk assessment and treatment. Assessment of the potential for benefit and risk from statin therapy for ASCVD prevention provides the framework for clinical decision making incorporating patient preferences.

*Percent reduction in LDL-C can be used as an indication of response and adherence to therapy, but is not in itself a treatment goal.

†The Pooled Cohort Equations can be used to estimate 10-year ASCVD risk in individuals with and without diabetes. The estimator within this application should be used to inform decision making in primary prevention patients not on a statin.

‡Consider moderate-intensity statin as more appropriate in low-risk individuals.

§For those in whom a risk assessment is uncertain, consider factors such as primary LDL-C ≥160 mg/dL or other evidence of genetic hyperlipidemias, family history of premature ASCVD with onset <55 years of age in a first-degree male relative or <65 years of age in a first-degree female relative, hs-CRP >2 mg/L, CAC score ≥300 Agatston units, or ≥75th percentile for age, sex, and ethnicity (for additional information, see http://www.mesa-nhlbi.org/CACReference.aspx), ABI <0.9, or lifetime risk of ASCVD. Additional factors that may aid in individual risk assessment may be identified in thefuture.

||Potential ASCVD risk-reduction benefits. The absolute reduction in ASCVD events from moderate- or high-intensity statin therapy can be approximated by multiplying the estimated 10-year ASCVD risk by the anticipated relative risk reduction from the intensity of statin initiated (~30% for moderate-intensity statin or ~45% for high-intensity statin therapy). The net ASCVD risk reduction benefit is estimated from the number of potential ASCVD events prevented with a statin compared to the number of potential excess adverse events.

¶Potential adverse effects. The excess risk of diabetes is the main consideration in ~0.1 excess cases per 100 individuals treated with a moderate-intensity statin for 1 year and ~0.3 excess cases per 100 individuals treated with a high-intensity statin for 1 year. In RCTs, both statin-treated and placebo-treated participants experienced the same rate of muscle symptoms. The actual rate of statin-related muscle symptoms in the clinical population is unclear. Muscle symptoms attributed to statin therapy should be evaluated (see Statin Safety Recommendations).

ABI indicates ankle-brachial index; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; RCT, randomized controlled trial.
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Intensities of Statin Therapy

High-Intensity Statin

Daily dose lowers LDL-C, on average by approximately ≥50%

  • Atorvastatin 40*-80 mg
  • Rosuvastatin 20-(40) mg

Moderate-Intensity Statin

Daily dose lowers LDL-C, on average by approximately 30% to <50%

  • Atorvastatin 10-(20) mg
  • Fluvastatin 40 mg bid
  • Fluvastatin XL 80 mg
  • Lovastatin 40 mg
  • Pitavastatin 2-4 mg
  • Pravastatin 40-(80) mg
  • Rosuvastatin (5)-10 mg
  • Simvastatin 20-40 mg**

Low-Intensity Statin

Daily dose lowers LDL-C, on average by approximately <30%

  • Fluvastatin 20-40 mg
  • Lovastatin 20 mg
  • Simvastatin 10 mg
  • Pitavastatin 1 mg
  • Pravastatin 10-20 mg

Statins and doses that are approved by the U.S. FDA but were not tested in the RCTs reviewed are listed in parentheses

*Evidence from 1 RCT (down-titration if unable to tolerate atorvastatin 80 mg)

**Initiation of or titration to simvastatin 80 mg is not recommended by the FDA due to increased risk of myopathy, including rhabdomyolysis
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Recommendations to Monitor Response to Statin Therapy

Statin Monitor Flowchart

*Fasting lipid panel preferred. In a nonfasting individual, a non-HDL–C >220 mg/dL may indicate genetic hypercholesterolemia that requires further evaluation or a secondary etiology. If nonfasting triglycerides are >500 mg/dL, a fasting lipid panel is required.

†In those already on a statin, in whom baseline LDL–C is unknown, an LDL–C <100 mg/dL was observed in mostindividuals receiving high-intensity statin therapy in RCT.s

‡Refer to Statin Safety Recommendations

Understanding Cardiovascular Risk

10-Year ASCVD Risk

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  • The 10-year calculated ASCVD risk is a quantitative estimation of absolute risk based upon data from representative population samples.
  • The 10-year risk estimate for "optimal risk factors" is represented by the following specific risk factor numbers for an individual of the same age, sex and race: Total cholesterol of 170 mg/dL, HDL-cholesterol of 50 mg/dL, untreated systolic blood pressure of 110 mm Hg, no diabetes history, and not a current smoker.
  • While the risk estimate is applied to individuals, it is based on group averages.
  • Just because two individuals have the same estimated risk does not mean that they will or will not have the same event of interest.
  • Example: If the 10-year ASCVD risk estimate is 10%, this indicates that among 100 patients with the entered risk factor profile, 10 would be expected to have a heart attack or stroke in the next 10 years.
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Lifetime ASCVD Risk

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  • The lifetime calculated ASCVD risk represents a quantitative estimation of absolute risk for a 50 year old man or woman with the same risk profile.
  • This estimation of risk is based on the grouping of risk factor levels into 5 strata.
    • All risk factors are optimal*
    • ≥1 risk factors are not optimal†
    • ≥1 risk factors are elevated‡
    • 1 major risk factor§
    • ≥2 major risk factors§
  • The division of lifetime risk by these 5 strata leads to thresholds in the data with large apparent changes in lifetime risk estimates.
  • Example: An individual that has all optimal risk factors except for a systolic blood pressure of 119 mm Hg has a lifetime ASCVD risk of 5%. In contrast, a similar individual that has all optimal risk factors except for a systolic blood pressure of 120 mm Hg has a lifetime ASCVD risk of 36%. This substantial difference in lifetime risk is due to the fact that they are in different stratum.

    • *Optimal risk levels for lifetime risk are represented by the simultaneous presence of all of the following: Untreated total cholesterol <180 mg/dL, untreated blood pressure <120/<80 mm Hg, no diabetes history, and not a current smoker †Nonoptimal risk levels for lifetime risk are represented by 1 or more of the following: Untreated total cholesterol of 180 to 199 mg/dL, untreated systolic blood pressure of 120 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg, and no diabetes history and not a current smoker

    ‡Elevated risk levels for lifetime risk are represented by 1 or more of the following: Untreated total cholesterol of 200 to 239 mg/dL, untreated systolic blood pressure of 140 to 159 mm Hg or diastolic blood pressure of 90 to 99 mm Hg, and no diabetes history and not a current smoker

    §Major risk levels for lifetime risk are represented by any of the following: Total cholesterol ≥240 mg/dL or treated, systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg or treated, or diabetes, or current smoker

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Lifestyle Recommendations

Diet recommendations for LDL-C lowering

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  1. Consume a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy products, poultry, fish, legumes, non-tropical vegetable oils and nuts; and limits intake of sweets, sugar-sweetened beverages, and red meats. (I A)
    • Adapt this dietary pattern to appropriate calorie requirements, personal and cultural food preferences, and nutrition therapy for other medical conditions (including diabetes mellitus).
    • Achieve this pattern by following plans such as the DASH dietary pattern, the USDA Food Pattern, or the AHA Diet.
  2. Aim for a dietary pattern that achieves 5-6% of calories from saturated fat. (I A)
  3. Reduce percent of calories from saturated fat. (I A)
  4. Reduce percent of calories from trans fat. (I A)

Diet recommendations for blood pressure lowering

  1. Consume a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy products, poultry, fish, legumes, non-tropical vegetable oils and nuts; and limits intake of sweets, sugar-sweetened beverages, and red meats. (I A)
    • Adapt this dietary pattern to appropriate calorie requirements, personal and cultural food preferences, and nutrition therapy for other medical conditions (including diabetes mellitus).
    • Achieve this pattern by following plans such as the DASH dietary pattern, the USDA Food Pattern, or the AHA Diet.
  2. Lower sodium intake. (I A)
  3. Consume no more than 2400 mg of sodium per day.
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Weight management recommendations

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Diets for weight loss

  1. Prescribe a diet to achieve reduced calorie intake for obese or overweight individuals who would benefit from weight loss, as part of a comprehensive lifestyle intervention with 1 of the following (I A):
    • 1200-1500 kcal/day for women and 1500-1800 kcal/day for men.
    • 500-750 kcal/day energy deficit.
    • Use one of the evidence-based diets that restricts certain food types (e.g., high-carbohydrate foods, low-fiber foods, or high-fat foods) in order to create an energy deficit by reduced food intake.
  2. Prescribe a calorie-restricted diet for obese or overweight individuals who would benefit from weight loss, based on the patient's preferences and health status, and preferably refer to a nutrition professional for counseling. (I A)

Lifestyle interventions and counseling for weight loss

  1. Advise participation in a comprehensive lifestyle program that assists participants in adhering to a lower calorie diet and increasing physical activity through the use of behavioral strategies. (I A)
  2. Prescribe on site, high-intensity (i.e., >14 sessions in 6 months) comprehensive weight loss interventions provided in individual or group sessions by a trained interventionist. (I A)
  3. Consider prescription of electronically delivered weight loss programs (including by telephone) that includes personalized feedback from a trained interventionist, recognizing that it may result in smaller weight loss than face-to-face interventions. (IIa A)
  4. Consider some commercial-based programs that provide comprehensive lifestyle interventions, provided there is peer-reviewed published evidence of their safety and efficacy. (IIa A)
  5. Consider a very low calorie diet (<800 kcal/day) only in limited circumstances and only when provided by trained practitioners in a medical care setting where medical monitoring and high intensity lifestyle intervention can be provided. (IIa A)
  6. Advise individuals who have lost weight to participate long term (>1 year) in a comprehensive weight loss maintenance program. (I A)
  7. Prescribe face-to-face or telephone-delivered weight loss maintenance programs that provide regular contact (> monthly) with a trained interventionist who helps participants engage in high levels of physical activity (i.e., 200-300 minutes/week), monitor body weight regularly (> weekly), and consume a reduced-calorie diet (need to lower body weight). (I A)

Selection criteria for bariatric surgical treatment of obesity

  1. Advise adults with a BMI ≥40 kg/m² or BMI ≥35 kg/m² with obesity-related co-morbid conditions who are motivated to lose weight and who have not responded to behavioral treatment with or without pharmacotherapy with sufficient weight loss to achieve targeted health outcome goals that bariatric surgery may be an appropriate option to improve health and offer referral to an experienced bariatric surgeon for consultation and evaluation. (IIa A)
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Physical activity recommendations

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Physical activity recommendations for modifying lipids and blood pressure lowering

  1. Advise adults to engage in aerobic physical activity to reduce LDL-cholesterol, non-HDL-cholesterol, and blood pressure. (IIa A)
    • Frequency: 3-4 sessions a week
    • Intensity: Moderate to vigorous
    • Duration: 40 minutes on average

Physical activity recommendations for secondary prevention*

  1. Aerobic exercise
    • Frequency: 3-5 days/week
    • Intensity: 50-80% of exercise capacity
    • Duration: 20-60 minutes
    • Modalities: Examples include walking, treadmill, cycling, rowing, stair climbing, and arm/leg ergometry
  2. Resistance exercise
    • Frequency: 2-3 days/week
    • Intensity: 10-15 repetitions/set to moderate fatigue
    • Duration: 1-3 sets of 8-10 upper and lower body exercises
    • Modalities: Examples include calisthenics, elastic bands, cuff/hand weights, dumbbells, free weights, wall pulleys, and weight machines

*Balady GJ et al. Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a Scientific Statement of the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation 2007;115:2675-2682

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Tobacco cessation recommendations

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5 R's for patients not ready to quit

  1. Relevance – Encourage the patient to indicate why quitting is personally relevant.
  2. Risks – Ask the patient to identify potential negative consequences of tobacco use.
  3. Rewards – Ask the patient to identify potential benefits of stopping tobacco use.
  4. Roadblocks – Ask the patient to identify barriers or impediments to quitting.
  5. Repetition – The motivational intervention should be repeated every time an unmotivated patient has an interaction with a clinician. Tobacco users who have failed in previous quit attempts should be told that most people make repeated quit attempts before they are successful.

5 A's for patients that are ready to quit

  1. Ask – Systematically identify all tobacco users at every visit.
  2. Advise – Strongly urge all smokers to quit.
  3. Assess – Identify smokers willing to make a quit attempt.
  4. Assist – Aid the patient in quitting.
  5. Arrange – Schedule follow-up contact.
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Summary of Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults

Summary of Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults

Recommendations
Click here for Definitions of Statin Intensity 		ACC/AHA COR ACC/AHA LOE
A. Heart-healthy lifestyle habits should be encouraged for all individuals.
B. The appropriate intensity of statin therapy should be initiated or continued:
1. Clinical ASCVD*
a. Age ≤75 y and no safety concerns: High-intensity statin I A
b. Age >75 y or safety concerns: Moderate-intensity statin I A
2. Primary prevention – Primary LDL-C ≥190 mg/dL
a. Rule out secondary causes of hyperlipidemia
b. Age ≥21y: High-intensity statin I B
c. Achieve at least a 50% reduction in LDL-C IIa B
d. LDL-C lowering nonstatin therapy may be considered to further reduce LDL-C IIb C
3. Primary prevention - Diabetes 40-75 years of age and LDL-C 70-189 mg/dL
a. Moderate-intensity statin I A
b. Consider high-intensity statin when ≥7.5% 10-y ASCVD risk using the Pooled Cohort Equations† IIa B
4. Primary prevention – No diabetes 40-75 years of age and LDL-C 70-189 mg/dL
a. Estimate 10-y ASCVD risk using the Risk Calculator based on the Pooled Cohort Equations† in those NOT receiving a statin; estimate risk every 4-6 y I B
b. To determine whether to initiate a statin, engage in a clinician-patient discussion of the potential for ASCVD risk reduction, adverse effects, drug–drug interactions, and patient preferences. IIa C
c. Re-emphasize heart-healthy lifestyle habits and address other risk factors.
i. ≥7.5% 10-y ASCVD risk: Moderate- or high-intensity statin I A
ii. 5 to <7.5% 10-y ASCVD risk: Consider moderate-intensity statin IIa B
iii. Other factors may be considered‡: LDL-C ≥160 mg/dL, family history of premature cardiovascular disease, hs-CRP ≥2.0 mg/L, CAC score ≥300 Agaston units, ABI <0.9 or lifetime ASCVD risk IIb C
5. Primary prevention when LDL-C <190 mg/dL and age <40 or >75 y, or <5% 10-y ASCVD risk
a. Statin therapy may be considered in selected individuals‡ IIb C
6. Statin therapy is not routinely recommended for individuals with NYHA class II-IV heart failure or who are receiving maintenance hemodialysis
C. Regularly monitor adherence to lifestyle and drug therapy with lipid and safety assessments.
Assess adherence, response to therapy, and adverse effects within 4-12 wk following statin initiation or change in therapy. I A
a. Measure a fasting lipid panel I A
b. Do not routinely monitor ALT or CK unless symptomatic IIa C
c. Screen and treat type 2 diabetes according to current practice guidelines. Heart-healthy lifestyle habits should be encouraged to prevent progression to diabetes I B
d. Anticipated therapeutic response approximately ≥50% reduction in LDL-C from baseline for high-intensity statin and 30% to <50% for moderate-intensity statin IIa B
i. Insufficient evidence for LDL-C or non–HDL-C treatment targets from RCTs
ii. For those with unknown baseline LDL-C, an LDL-C <100 mg/dL was observed in RCTs of high-intensity statin therapy
e. Less than anticipated therapeutic response:
i. Reinforce improved adherence to lifestyle and drug therapy I A
ii. Evaluate for secondary causes of hyperlipidemia if indicated I A
iii. Increase statin intensity, or if on maximally-tolerated statin intensity, consider addition of nonstatin therapy in selected high-risk individuals§ IIb C
f. Regularly monitor adherence to lifestyle and drug therapy every 3-12 mo once adherence has been established. Continued assessment of adherence for optimal ASCVD risk reduction and safety. I A
D. In individuals intolerant of the recommended intensity of statin therapy, use the maximally-tolerated intensity of statin. I B
1. If there are muscle or other symptoms, establish that they are related to the statin IIa B
2. For specific recommendations on managing muscle symptoms (see Statin Safety Recommendations)

*Clinical ASCVD includes acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin.


†Estimated 10-year or “hard” ASCVD risk includes first occurrence of nonfatal MI, CHD death, and nonfatal and fatal stroke as used by the Risk Assessment Work Group in developing the Pooled Cohort Equations.


‡These factors may include primary LDL-C ≥160 mg/dL or other evidence of genetic hyperlipidemias; family history of premature ASCVD with onset <55 years of age in a first-degree male relative or <65 years of age in a first-degree female relative; hs-CRP ≥2 mg/L; CAC score ≥300 Agatston units or ≥75 th percentile for age, sex, and ethnicity; ABI <0.9; or lifetime risk of ASCVD. Additional factors that might aid in individual risk assessment could be identified in the future.


§High-risk individuals include those with clinical ASCVD, an untreated LDL-C ≥190 mg/dL suggesting genetic hypercholesterolemia, or diabetes.


ABI indicates ankle-brachial index; ACC, American College of Cardiology; AHA, American Heart Association; ALT, alanine aminotransferase, a test of hepatic function; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CHD, coronary heart disease; CK, creatine kinase, a test of muscle injury; COR, Class of Recommendation; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; LOE, Level of Evidence; NHLBI, National Heart, Lung, and Blood Institute; NYHA, New York Heart Association; RCTs, randomized controlled trials; and TIA, transient ischemic attack.

References

Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25_PA):2889-2934. doi:10.1016/j.jacc.2013.11.002.

Statin Prescribing Information

(For purposes of this app, prescribing information was last accessed on 2/4/2015 through pharmaceutical company websites. For your reference, see below for links to most updated PIs.)

Consulted Resources

Bruckert, Eric, Gilles Hayem, Sylvie Dejager, Caroline Yau, and Bernard Bégaud. "Mild to Moderate Muscular Symptoms with High-Dosage Statin Therapy in Hyperlipidemic Patients —The PRIMO Study." Cardiovascular Drugs and Therapy 19.6 (2005): 403-14

Jacobson TA, NLA Task Force on Statin Safety-2014 Update. J of Clinical Lipidology. May-June 2014;8(3):S1-S4

Long, J., “What to Do When the Patient Cannot Tolerate Statins: Alternative Therapies” Proceedings of the American College of Cardiology Scientific Sessions 2013. Compiled Reseach.

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External Links to Full Guidelines and More Information

Click here for 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk

Click here for 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

Click here for 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults

Click here for 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk

Click here for 2008 AHRQ Guideline on Treating Tobacco Use and Dependence

Click here for ACC Dyslipidemia Clinical Community

Click here for ACC Cardiometabolic Clinical Community

Click here for Clinical Vignettes

Click here for Blood Cholesterol Guideline

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Patient References

Groups that Benefit from Statin Therapy

Benifit Group Infographic

More Information

Please go to cardiosmart.org to find more information about how to prevent, treat, and manage cardiovascular disease.
https://www.cardiosmart.org/About

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Other Mobile Resources

Download ACC Guideline Clinical App

Download ASCVD Risk Estimator mobile app

ASCVD Risk Estimator web application
http://tools.acc.org/ASCVD-Risk-Estimator-Plus

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Lipid Manager Terms of Service and License Agreement

This Terms of Service and License Agreement constitutes a legal agreement (collectively, the "Agreement") between the American College of Cardiology Foundation ("ACCF") and You and your agents ("You") for the use of the Lipid Manager, which links the LDL-C Lowering Therapy, Hypertriglyceridemia, and the Statin Intolerance tools (collectively "the Product"), whether You use the mobile application version of the Product or the web version of the Product. The Product allows You to access certain content included in the Product ("Content") relating to reducing ASCVD risk by managing patients’ LDL-C and triglycerides and corresponding clinical policy.

By using the Product, You accept and agree to be bound by all of the terms and conditions set forth in this Agreement. If You do not wish to accept the terms and conditions of this Agreement, You may not proceed to use the Product.

ACCF may change the terms of this Agreement from time to time without further notice directly to You. When the terms are changed, ACCF will post a general conspicuous notice. If You do not agree with the revised terms, please discontinue use of the Product immediately. Your continued use of the Product following such notice constitutes your acceptance of and agreement to be bound by any revised terms of the Agreement. This Agreement expressly incorporates by reference and includes rules or disclaimers that may be posted and updated within the Product or communicated to You from time to time.


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ACCF may terminate your access and/or the Product at any time. You agree that any termination of your access to the Product shall not result in any liability or other obligation of ACCF to You, or any third party in connection with such termination.


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This Product, including the information, text, graphics, images, audio and video files, trademarks and other materials that may be contained therein (collectively "Content"), is owned by ACCF and/or its suppliers or acknowledged licensors, and is protected by patents, copyrights, trademarks, and other proprietary rights. Except as specifically provided in this Agreement, your use of the Product shall be governed and constrained by applicable patent, copyright, trademark and other intellectual property laws. ACCF grants You a limited, nonexclusive, nontransferable, revocable license to utilize and access the Product for your noncommercial, personal use according to the terms and conditions in this Agreement. You may not modify, publish, transmit, participate in the transfer or sale of, reproduce, create derivative works from, distribute, perform, display, incorporate into another website, or in any other way exploit the Service and/or any of the Content, in whole or in part. Except as expressly granted by this Agreement, You acquire no right, title or interest in the Product or the Content or other data or materials incorporated in the Product. ACCF, ACC or affiliates or licensors thereof shall retain all right, title and interest in the Product and Content.


PREVENT™ TERMS AND CONDITIONS

Disclaimer: The information derived from the use of PREVENTTM is based on PREVENTTM 1.0.0. Updates and future adaptations of PREVENTTM may yield different results and conclusions.

Attribution Statement: The PREVENTTM equations were developed by select members of the American Heart Association Cardiovascular-Kidney-Metabolic Scientific Advisory Group. The risk equations were derived and validated in a large, diverse sample of over 6 million individuals.[1], [2]

  • [1] Khan SS, Matsushita K, Sang Y, et al. Development and Validation of the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENTTM) Equations. Circulation 2023. DOI: 10.1161/CIRCULATIONAHA.123.067626(link opens in new window).
  • [2] Khan SS, Coresh J, Pencina MJ, et al. Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association. Circulation 2023;148(24):1982-2004. DOI: 10.1161/CIR.0000000000001191(link opens in new window).

Non-Affiliation Statement: The ACCF is an independent entity and is not affiliated with, endorsed by, sponsored by, or approved by American Heart Association (“AHA”). Use of the PREVENTTM risk model and related materials is pursuant to a license from AHA and does not imply any partnership or association between AHA and ACCF.


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You assume all risks associated with use of the Product including, but not limited to any harm, injury or damages resulting directly or indirectly from the use of the Product, all such risks being known and understood by You. In consideration of your use of the Product, You, for yourself and anyone entitled to act on your behalf, waive and forever release ACCF, its officers, trustees, employees, representatives and successors from all claims and liabilities of any kind arising out of your use or misuse of the Product.


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About the App

When was this App last updated?

May 2026

How can I provide feedback?

Click here to fill out our feedback survey

What is the target patient population for this app?

The ACC Lipid Manager app is meant to be used in relation to patients who may need lifestyle intervention or drug therapy to lower their triglycerides and/or LDL-C, particularly with the goal to lower their risk for heart disease and stroke.

How is this App intended to be used?

The ACC Lipid Manager app contains three tools to help clinicians manage a patient’s CV risk from therapy initiation through treatment calibration with a goal of lowering ASCVD risk:

  • LDL-C Lowering Therapy tool: Determine which lipid-lowering therapies should be considered and in what order
  • Statin Intolerance tool: Evaluate patient for possible statin intolerance, and determine appropriate next steps
  • Hypertriglyceridemia tool: Use the app to see tailored consensus recommendations for both lifestyle intervention and pharmacological management of high-risk patients with persistent hypertriglyceridemia
Clinicians can also email themselves the results from each individual tool to include as part of their records.

Each tool within the app is designed to be used on its own or in combination to manage a patient’s therapy throughout their continuum of care. The Lipid Manager App aims to streamline use at point of care by offering access to all of ACC’s Lipid management tools from one place. This app’s tools also include the American Heart Association’s PREVENT™-ASCVD risk estimator for determining 10-year (and in some cases 30-year) risk as part of their internal treatment workflows.

LDL-C Lowering Therapy is a tool that helps clinicians navigate guidance for lowering LDL-C and reducing ASCVD risk in adult patients. Advice also includes considerations for managing patients with statin-attributed muscle symptoms and further considerations for managing subclinical atherosclerosis (if applicable). Guidance from the LDL-C Lowering Therapy tool is derived from the 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia and the prescribing information for lipid-lowering therapies.

The ACC Statin Intolerance App guides clinicians through the process of managing and treating patients who report muscle symptoms while on statin therapy to:

  • evaluate possible statin intolerance
  • conduct follow up steps for treating and managing a patient who reports muscle symptoms while on a statin, and
  • determine the best course of therapy for their patients.

The information and recommendations in this app are derived from the 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia, the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, and the prescribing information for each statin.

Hypertriglyceridemia is a tool based on the 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia. The Hypertriglyceridemia tool has not yet been updated with content from the 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia – an update is planned by July, 2026. Consensus recommendations are provided for clinicians and patients regarding unique aspects of lifestyle interventions for management of hypertriglyceridemia and the use of statins and triglyceride risk-based nonstatin therapies for ASCVD risk reduction in the following patient groups with persistent hypertriglyceridemia:

  1. patients with established ASCVD;
  2. patients with diabetes mellitus and additional risk factor(s);
  3. high-risk primary prevention patients; and
  4. patients with severe hypertriglyceridemia

The information and recommendations in this App and all its component tools are meant to support clinical decision making. They are not meant to represent the only or best course of care or replace clinical judgment. Therapeutic options should be determined after discussion between the patient and their care provider.

How was this App developed?

Tools within the app were designed and vetted through collaboration with writing committee members from each of the ACC clinical policy source documents. It was further refined via user testing with physicians, nurse practitioners, pharmacists, and other specialties.

The PREVENT™ equations were developed by select members of the American Heart Association Cardiovascular-Kidney-Metabolic Scientific Advisory Group. The risk equations were derived and validated in a large, diverse sample of over 6 million individuals.

  • Khan SS, Matsushita K, Sang Y, et al. Development and Validation of the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENTTM) Equations. Circulation 2023. DOI: 10.1161/CIRCULATIONAHA.123.067626.
  • Khan SS, Coresh J, Pencina MJ, et al. Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association. Circulation 2023;148(24):1982-2004. DOI: 10.1161/CIR.0000000000001191.

The information derived from the use of PREVENT™ is based on PREVENT™ 1.0.0. Updates and future adaptations of PREVENT™ may yield different results and conclusions.

Financial support for Lipid Manager was provided by Esperion. All content was independently developed with no sponsor involvement.

Please see the Resources section of this App for links to additional references.

For Support
Call: (202) 375-6000, ext. 5603 or (800) 253-4636
Email: membercare@acc.org

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Lab Guidance

Muscle symptom severity

  • Creatine Kinase (CK) Level

Rhabdomyolysis

  • Creatinine
  • Urinalysis (particularly myoglobin)

Risk Factors/Secondary Causes

  • Thyroid panel (particularly TSH)
  • Hepatic panel (particularly ALT)
  • Electrolyte panel
  • Renal panel
  • ERS (erythrocyte sedimentation rate)
  • Vitamin D 25-OH level
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Lab Guidance

Muscle symptom severity

  • Creatine Kinase (CK) Level

Rhabdomyolysis

  • Creatinine
  • Urinalysis (particularly myoglobin)

Risk Factors/Secondary Causes

  • Thyroid panel (particularly TSH)
  • Hepatic panel (particularly ALT)
  • Electrolyte panel
  • Renal panel
  • ERS (erythrocyte sedimentation rate)
  • Vitamin D 25-OH level
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CK Level Information

  • Baseline CK is reasonable to measure prior to statin therapy in individuals at increased risk for adverse muscle events (IIA, C).
  • During statin therapy, it is reasonable to measure CK in individuals with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue. (IIA, C).
  • Standard CK ranges may vary by lab. Mayo Clinic defines standard CK levels as:
    • Males 18+ : 52-336 U/L
    • Females 18+: 38-176 U/L
  • Severe CK elevation, with possible indication for rhabdomyolysis, may be considered to be > 5x ULN. Using Mayo ranges, > 5x ULN =
    • Male: CK > 1680 U/L
    • Female: CK > 880 U/L
  • Some CK elevation above standard levels is characteristic in patients with any of the following criteria:
    • physical exertion (It is best to wait 48 hours to after acute heavy exercise before taking any CK measurement.)
    • ethnicity (blacks and particularly black insulin users-DM)
    • alcoholism
    • illicit drugs (amphetamine or cocaine)
    • atypical antipsychotics
    • hypothyroidism
    • metabolic or inflammatory myopathies
    • neuropathy or radiculopathy
    • seizures
    • trauma
    • idiopathic causes
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Select any secondary medications

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The following is derived mainly from statin prescribing information and is not a comprehensive list of all possible interacting medications. Consult a pharmacist for a full evaluation of drug-drug interactions.

Medication types that increase risk for statin adverse effects include:

  • Fibrates (e.g., gemfibrozil, fenofibrate)
  • Niacin ≥ 1 gram
  • Strong CYP3A4 inhibitors
  • Immunosuppressants (e.g., cyclosporine A, azathioprine)
  • Hepatitis C protease inhibitors
  • Antiretrovirals
  • Glucocorticoids

Medication types that predispose individuals to non-statin-related muscle symptoms include:

  • Antiretrovirals
  • Glucocorticoids
  • Atypical antipsychotics
  • Neurol eptics and psychotropic agents (e.g., haloperidol, risperidone)
  • Antiviral agents (e.g., zidovudine, ritonavir, dida osine)
  • Analgesics and antiinflammatory drugs (e.g., salicylates, nonsteroidal antiinflammatory drugs, glucocorticoids)
  • Anesthetics and neuromuscular blocking agents (e.g., propofol, ketamine, succinylcholine)

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Select any secondary medications

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top

The following is derived mainly from statin prescribing information and is not a comprehensive list of all possible interacting medications. Consult a pharmacist for a full evaluation of drug-drug interactions.

Medication types that increase risk for statin adverse effects include:

  • Fibrates (e.g., gemfibrozil, fenofibrate)
  • Niacin ≥ 1 gram
  • Strong CYP3A4 inhibitors
  • Immunosuppressants (e.g., cyclosporine A, azathioprine)
  • Hepatitis C protease inhibitors
  • Antiretrovirals
  • Glucocorticoids

Medication types that predispose individuals to non-statin-related muscle symptoms include:

  • Antiretrovirals
  • Glucocorticoids
  • Atypical antipsychotics
  • Neurol eptics and psychotropic agents (e.g., haloperidol, risperidone)
  • Antiviral agents (e.g., zidovudine, ritonavir, dida osine)
  • Analgesics and antiinflammatory drugs (e.g., salicylates, nonsteroidal antiinflammatory drugs, glucocorticoids)
  • Anesthetics and neuromuscular blocking agents (e.g., propofol, ketamine, succinylcholine)
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Risk Factors Worksheet

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Secondary Medications

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The following is derived mainly from statin prescribing information and is not a comprehensive list of all possible interacting medications. Consult a pharmacist for a full evaluation of drug-drug interactions.

Medication types that increase risk for statin adverse effects include:

  • Fibrates (e.g., gemfibrozil, fenofibrate)
  • Niacin ≥ 1 gram
  • Strong CYP3A4 inhibitors
  • Immunosuppressants (e.g., cyclosporine A, azathioprine)
  • Hepatitis C protease inhibitors
  • Antiretrovirals
  • Glucocorticoids

Medication types that predispose individuals to non-statin-related muscle symptoms include:

  • Antiretrovirals
  • Glucocorticoids
  • Atypical antipsychotics
  • Neurol eptics and psychotropic agents (e.g., haloperidol, risperidone)
  • Antiviral agents (e.g., zidovudine, ritonavir, dida osine)
  • Analgesics and antiinflammatory drugs (e.g., salicylates, nonsteroidal antiinflammatory drugs, glucocorticoids)
  • Anesthetics and neuromuscular blocking agents (e.g., propofol, ketamine, succinylcholine)
Select all that Apply
Back

Secondary Medications

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top

The following is derived mainly from statin prescribing information and is not a comprehensive list of all possible interacting medications. Consult a pharmacist for a full evaluation of drug-drug interactions.

Medication types that increase risk for statin adverse effects include:

  • Fibrates (e.g., gemfibrozil, fenofibrate)
  • Niacin ≥ 1 gram
  • Strong CYP3A4 inhibitors
  • Immunosuppressants (e.g., cyclosporine A, azathioprine)
  • Hepatitis C protease inhibitors
  • Antiretrovirals
  • Glucocorticoids

Medication types that predispose individuals to non-statin-related muscle symptoms include:

  • Antiretrovirals
  • Glucocorticoids
  • Atypical antipsychotics
  • Neurol eptics and psychotropic agents (e.g., haloperidol, risperidone)
  • Antiviral agents (e.g., zidovudine, ritonavir, dida osine)
  • Analgesics and antiinflammatory drugs (e.g., salicylates, nonsteroidal antiinflammatory drugs, glucocorticoids)
  • Anesthetics and neuromuscular blocking agents (e.g., propofol, ketamine, succinylcholine)

Select all that Apply

Clear Selections Done Selecting
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Secondary Medications

close
top

The following is derived mainly from statin prescribing information and is not a comprehensive list of all possible interacting medications. Consult a pharmacist for a full evaluation of drug-drug interactions.

Medication types that increase risk for statin adverse effects include:

  • Fibrates (e.g., gemfibrozil, fenofibrate)
  • Niacin ≥ 1 gram
  • Strong CYP3A4 inhibitors
  • Immunosuppressants (e.g., cyclosporine A, azathioprine)
  • Hepatitis C protease inhibitors
  • Antiretrovirals
  • Glucocorticoids

Medication types that predispose individuals to non-statin-related muscle symptoms include:

  • Antiretrovirals
  • Glucocorticoids
  • Atypical antipsychotics
  • Neurol eptics and psychotropic agents (e.g., haloperidol, risperidone)
  • Antiviral agents (e.g., zidovudine, ritonavir, dida osine)
  • Analgesics and antiinflammatory drugs (e.g., salicylates, nonsteroidal antiinflammatory drugs, glucocorticoids)
  • Anesthetics and neuromuscular blocking agents (e.g., propofol, ketamine, succinylcholine)

Select all that Apply

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Muscle pain worksheet

0 = No Pain to 10 = Worst Pain Imaginable

Impact on everyday activities

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Possible alternate causes of muscle symptoms

Select all that apply
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Statin Safety Recommendations

Statin Selection

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To maximize the safety of statins, selection of the appropriate statin and dose in men and nonpregnant/nonnursing women should be based on patient characteristics, level of ASCVD risk, and potential for adverse effects. Moderate-intensity statin therapy should be used in individuals in whom high-intensity statin therapy would otherwise be recommended when characteristics predisposing them to statin associated adverse effects are present.

Characteristics predisposing individuals to statin adverse effects include, but are not limited to:

  • Multiple or serious comorbidities, including impaired renal or hepatic function.
  • History of previous statin intolerance or muscle disorders.
  • Unexplained ALT elevations >3 times ULN.
  • Patient characteristics or concomitant use of drugs affecting statin metabolism.
  • ≥ 75 years of age.

Additional characteristics that may modify the decision to use higher statin intensities may include, but are not limited to:

  • History of hemorrhagic stroke.
  • Asian ancestry.
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Statin Dosage

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  • Decreasing the statin dose may be considered when 2 consecutive values of LDL-C levels are <40 mg/dL.
  • It may be harmful to initiate simvastatin at 80 mg daily or increase the dose of simvastatin to 80 mg daily. (III A)
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Creatine Kinase (CK)

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  • CK should not be routinely measured in individuals receiving statin therapy. (III A)
  • Baseline measurement of CK is reasonable for individuals believed to be at increased risk for adverse muscle events based on a personal or family history of statin intolerance or muscle disease, clinical presentation, or concomitant drug therapy that might increase the risk for myopathy.
  • During statin therapy, it is reasonable to measure CK in individuals with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue. (II C)
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Muscle Symptoms

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It is reasonable to evaluate and treat muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue, in statin-treated patients according to the following management algorithm: (IIa B)

  • To avoid unnecessary discontinuation of statins, obtain a history of prior or current muscle symptoms to establish a baseline before initiating statin therapy.
  • If unexplained severe muscle symptoms or fatigue develop during statin therapy, promptly discontinue the statin and address the possibility of rhabdomyolysis by evaluating CK, creatinine, and a urinalysis for myoglobinuria.
  • If mild to moderate muscle symptoms develop during statin therapy:
    • Discontinue the statin until the symptoms can be evaluated.
    • Evaluate the patient for other conditions that might increase the risk for muscle symptoms (e.g., hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases).
    • If muscle symptoms resolve, and if no contraindication exists, give the patient the original or a lower dose of the same statin to establish a causal relationship between the muscle symptoms and statin therapy.
    • If a causal relationship exists, discontinue the original statin. Once muscle symptoms resolve, use a low dose of a different statin.
    • Once a low dose of a statin is tolerated, gradually increase the dose as tolerated.
    • If, after 2 months without statin treatment, muscle symptoms or elevated CK levels do not resolve completely, consider other causes of muscle symptoms listed above.
    • If persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume statin therapy at the original dose.
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Hepatic Function

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  • Baseline measurement of hepatic transaminase levels (ALT) should be performed before initiating statin therapy.
  • During statin therapy, it is reasonable to measure hepatic function if symptoms suggesting hepatotoxicity arise (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine or yellowing of the skin or sclera).
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Diabetes

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Individuals receiving statin therapy should be evaluated for new-onset diabetes mellitus according to the current diabetes screening guidelines. Those who develop diabetes mellitus during statin therapy should be encouraged to adhere to a heart healthy dietary pattern, engage in physical activity, achieve and maintain a healthy body weight, cease tobacco use, and continue statin therapy to reduce their risk of ASCVD events.

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Age and Drug Regimen Consideration

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For individuals taking any dose of statins, it is reasonable to use caution in individuals >75 years of age, as well as in individuals that are taking concomitant medications that alter drug metabolism, taking multiple drugs, or taking drugs for conditions that require complex medication regimens (e.g., those who have undergone solid organ transplantation or are receiving treatment for HIV). A review of the manufacturer's prescribing information may be useful before initiating any cholesterol-lowering drug.

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Cognitive Impairment

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For individuals presenting with a confusional state or memory impairment while on statin therapy, it may be reasonable to evaluate the patient for nonstatin causes, such as exposure to other drugs, as well as for systemic and neuropsychiatric causes, in addition to the possibility of adverse effects associated with statin drug therapy.

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