Welcome to ACC’s Statin Intolerance Tool

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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

Rhabdomyolysis Assessment

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.

Muscle Symptoms Type, Severity, and Secondary Causes

Symptom Type

Symptom Area

Onset of muscle symptoms predates current statin prescription. It is unlikely symptoms are statin-related.

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.

Demographics Possible predispositions to muscle symptoms

Sex
Age
Yrs Years

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.

When did the patient start the statin?

Onset of muscle symptoms predates current statin prescription. It is unlikely symptoms are statin-related.
(e.g., fenofibrates, strong CYP3A4 inhibitors)

Likelihood of Statin-Related Muscle Symptoms with Current Prescription

Statin: Dose: | Frequency:


Statin-Related Muscle Symptoms Statin-Related Muscle Symptoms
Value Result Possible Possible Unlikely Unlikely
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/

Next Steps


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

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

Dose Legend

Boldface type indicates specific statins and doses that were evaluated in RCTs (1617,1846,4748,49) 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.

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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  • * ACC/AHA Guideline Recommendation

Current Follow-Up

Labs have been returned.
Has a non-statin cause for muscle symptoms been identified?

Recommendation

Next Steps
  • Treat identified cause of muscle symptoms.
  • If CK is elevated above 5x 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.

Recommendation

Next Steps
  • If CK is elevated above 5x 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.

Current Follow-Up

Patient was taken off original statin
Did muscle symptoms resolve after statin discontinuation?

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 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

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.

Current Follow-Up

Patient has been rechallenged with original statin
Did muscle symptoms return after rechallenge?

Recommendation

Next Steps
  • Stop original statin.
  • Wait for 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 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

Recommendation

Next Steps
  • Continue with current statin prescription.

Current Follow-Up

Considering starting patient on alternative statin

Considering alternative statin because:

  • 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 muscle symptoms?

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 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

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 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

Muscle symptoms returned after starting an alternate statin.

Current Follow-Up
Were any non-statin causes for muscle symptoms identified?

Recommendation

Next Steps
  • Treat identified cause of 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.
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 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).

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

Dose Legend

Boldface type indicates specific statins and doses that were evaluated in RCTs (1617,1846,4748,49) 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.

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

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Statin’s Interactions with Drugs You Have Selected
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Statin’s Interactions with All Listed Secondary Drugs

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  • § Expert Opinion
  • ‡ FDA Recommendation
  • * ACC/AHA Guideline Recommendation

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Select Statin Characteristic



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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

Low Intensity

Moderate Intensity

High Intensity

Legend - Dosing: Boldface

Dose Legend

Boldface type indicates specific statins and doses that were evaluated in RCTs (1617,1846,4748,49) 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.

Statin Safety Recommendations

Statin Selection

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.

Statin Dosage

  • 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)

Creatine Kinase (CK)

  • 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)

Muscle Symptoms

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.

Hepatic Function

  • 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).

Diabetes

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.

Age and Drug Regimen Consideration

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.

Cognitive Impairment

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.

Groups that Benefit from Statin Therapy

Secondary Prevention: Clinical ASCVD

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)

Primary Prevention: LDL-C ≥190mg/dL

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.

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

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)

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

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.

Additional Factors

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

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.

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

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

  • 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.

Lifetime ASCVD Risk

  • 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

Lifestyle Recommendations

Diet recommendations for LDL-C 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. 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.

Weight management recommendations

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)

Physical activity recommendations

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

Tobacco cessation recommendations

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.

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.

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

Terms of Service

Disclaimer

By using this application and its content, you accept and agree to be bound by the following terms and conditions.

This Application was produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of publication. The results and recommendations provided by this application are not intended to, and should not, replace clinical judgment of the care provider. Further, the material is not intended to present the only, or necessarily the best, methods of procedures for the medical situation, but rather is intended to represent an approach, view, statement, or opinion. The content in this product is presented as an educational service intended for licensed healthcare professionals. Therapeutic options should be determined after discussion between the patient and their care provider.

You hereby agree to indemnify, defend, and hold ACCF, its directors, officers, shareholders, parents, subsidiaries, affiliates, agents, and licensors harmless from and against any and all liability, losses, damages, and costs, including, without limitation, reasonable attorney’s fees and costs, incurred in connection with any claim arising from your use of this application or its content.

©The American College of Cardiology Foundation 2015

All Rights Reserved. The content of this app has been published for personal and educational use only. No commercial use is authorized.

About the App

This app was last updated on: May 2017

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How is this app intended to be used?
ACC’s Statin Intolerance App uses clinical guidelines and best practices to help clinical professionals

  • 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 recommendations in the app 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?
The app was further refined and vetted by physicians, physician assistants, nurse practitioners, pharmacists, and other relevant specialties; and through user testing in care settings with patients.

This app was developed as part of the ACC's LDL: Address the Risk Initiative. Financial support for the LDL: Address the Risk Initiative was provided by Amgen Inc. All of the content was independently developed with no sponsor involvement.

For Support
Call: (202)-375-6000, ext. 5603
Or (800) 253-4636
Fax: (202) 375-7000
Email: resource@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

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

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

Select any secondary medications

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

Select any secondary medications

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)

Risk Factors Worksheet

Select all that apply

Secondary Medications

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

Secondary Medications

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

Secondary Medications

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

Muscle pain worksheet

0 = No Pain to 10 = Worst Pain Imaginable

Impact on everyday activities

Possible alternate causes of muscle symptoms

Select all that apply

Statin Safety Recommendations

Statin Selection

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.

Statin Dosage

  • 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)

Creatine Kinase (CK)

  • 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)

Muscle Symptoms

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.

Hepatic Function

  • 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).

Diabetes

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.

Age and Drug Regimen Consideration

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.

Cognitive Impairment

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.