Table 1. Summary of Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults
|Recommendations||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 ASCVDa|
|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 (Table 3)||I||B|
|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 Equationsb||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 Equationsb 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. Re-emphasize heart-healthy lifestyle habits and address other risk factors.||IIa||C|
|i. ≥7.5% 10-y ASCVD risk:|
Moderate- or high-intensity statin
|ii. 5 to <7.5% 10-y ASCVD risk:|
Consider moderate-intensity statin
|iii. Other factors may be consideredc:|
LDL-C ≥160 mg/dL, family history of premature ASCVD, hs-CRP ≥2.0 mg/L, CAC score ≥300 Agaston units, ABI <0.9 or lifetime ASCVD risk
|5. Primary prevention when LDL-C <190 mg/dL and age <40 or >75 y, or <5% 10-y ASCVD risk||IIb||C|
|a. Statin therapy may be considered in selected individuals when a risk decision is uncertain.c|
|6. The panel makes no recommendation for initiation of statin therapy 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.|
|1. 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 (Table 3)||I||A|
|iii. Increase statin intensity, or if on maximally-tolerated statin intensity, consider addition of nonstatin therapy in selected high-risk individualsd||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 (Table 8)|
|a 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.|
b 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 (http://www.cardiosource.org/en/Science-And-Quality/Practice-Guidelines-and-Quality-Standards/2013-Prevention-Guideline-Tools.aspx or http://my.americanheart.org/cvriskcalculator).
c 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 ≥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 might aid in individual risk assessment could be identified in the future.
d High-risk individuals include those with clinical ASCVD, an untreated LDL-C ≥190 mg/dL suggesting genetic hypercholesterolemia, or diabetes 40-75 years of age and LDL-C 70-189 mg/dL.
Table 2. High- Moderate- and Low-Intensity Statin Therapy (Used in the RCTs reviewed by the Expert Panel)a
|Daily dose lowers LDL-C on average by approximately ≥50%||Daily dose lowers LDL-C on average by approximately 30%-<50%||Daily dose lowers LDL-C on average by <30%|
|Atorvastatin (40b)-80 mg|
Rosuvastatin 20 (40) mg
|Atorvastatin 10 (20) mg|
Rosuvastatin (5) 10 mg
Simvastatin 20-40 mgc
Pravastatin 40 (80) mg
Lovastatin 40 mg
Fluvastatin XL 80 mg
Fluvastatin 40 mg
bid Pitavastatin 2-4 mg
|Simvastatin 10 mg|
Pravastatin 10-20 mg
Lovastatin 20 mg
Fluvastatin 20-40 mg
Pitavastatin 1 mg
|Boldface type indicates specific statins and doses that were evaluated in RCTs. All of these RCTs demonstrated a reduction in major cardiovascular events. Italic type indicates statins and doses that have been approved by the FDA but were not tested in the RCTs reviewed.|
a 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.
b Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study.
c 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.
Table 3. Secondary Causes of Hyperlipidemia Most Commonly Encountered in Clinical Practice
|Secondary Cause||Elevated LDL-C||Elevated Triglycerides|
|Diet||Saturated or trans fats, weight gain, anorexia||Weight gain, very low-fat diets, high intake of refined carbohydrates, excessive alcohol intake|
|Drugs||Diuretics, cyclosporine, glucocorticoids, amiodarone||Oral estrogens, glucocorticoids, bile acid sequestrants, protease inhibitors, retinoic acid, anabolic steroids, sirolimus, raloxifene, tamoxifen, beta blockers (not carvedilol), thiazides|
|Diseases||Biliary obstruction, nephrotic syndrome||Nephrotic syndrome, chronic renal failure, lipodystrophies|
|Disorders and altered states of metabolism||Hypothyroidism, obesity, pregnancya||Diabetes (poorly controlled), hypothyroidism, obesity; pregnancya|
|a Cholesterol and triglycerides rise progressively throughout pregnancy. Treatment with statins, niacin, and ezetimibe are contraindicated during pregnancy and lactation|
Table 4. Recommendations for Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults—Statin Treatment (High-, moderate-, and low-statin intensities are defined in Table 2)
- Treatment Targets
- The panel makes no recommendations for or against specific LDL-C or non-HDL-C targets for the primary or secondary prevention of ASCVD.
- Secondary Prevention
- High-intensity statin therapy should be initiated or continued as first-line therapy in women and men ≤75 years of age who have clinical ASCVDa, unless contraindicated. (I-A)
- In individuals with clinical ASCVDa in whom high-intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicatedb or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated (Table 5 for Safety of Statins, Recommendation 1). (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 in Individuals ≥21 Years of Age With LDL-C ≥190 mg/dL
- Individuals with LDL-C ≥190 mg/dL or triglycerides ≥500 mg/dL should be evaluated for secondary causes of hyperlipidemia (Table 1). (Ic-B)
- Adults ≥21 years of age with primary LDL-C ≥190 mg/dL should be treated with statin therapy (10-year ASCVD risk estimation is not required): (Id-B)
- 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. (IIb-C)
- Primary Prevention in Individuals With Diabetes and LDL-C 70-189 mg/dL
- Moderate-intensity statin therapy should be initiated or continued for adults 40-75 years of age with diabetes mellitus. (I-A)
- High-intensity statin therapy is reasonable for adults 40-75 years of age with diabetes mellitus with a ≥7.5% estimated 10-year ASCVD riske unless contraindicated. (IIa-B)
- In adults with diabetes mellitus, who are <40 or >75 years of age or with LDL-C <70 mg/dL, it is reasonable to evaluate the potential for ASCVD benefits and for adverse effects and drug–drug interactions and to consider patient preferences when deciding to initiate, continue, or intensify statin therapy. (IIa-C)
- Primary Prevention in Individuals Without Diabetes and With LDL-C 70-189 mg/dL
- The Pooled Cohort Equations should be used to estimate
10-year ASCVD riske for individuals with LDL-C 70-189 mg/dL without clinical ASCVDa to guide initiation of statin therapy for the primary prevention of ASCVD. (Ic-B)
- The Pooled Cohort Equations should be used to estimate
- Adults 40-75 years of age with LDL-C 70-189 mg/dL, without clinical ASCVDa or diabetes, and with an estimated 10-year ASCVD riske ≥7.5% should be treated with moderate- to high-intensity statin therapy. (Id-A)
- It is reasonable to offer treatment with a moderate-intensity statin to adults 40-75 years of age, with LDL-C 70-189 mg/dL, without clinical ASCVDa or diabetes and an estimated 10-year ASCVD riske of 5% to <7.5%. (IIa-B)
- Before initiating statin therapy for the primary prevention of ASCVD in adults with LDL-C 70-189 mg/dL without clinical ASCVDa 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, as well as patient preferences for treatment. (IIa-C)
- 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 factorsf 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, and drug–drug interactions and consider patient preferences. (IIb-C)
- Heart Failure and Hemodialysis
- The Expert Panel makes no recommendations regarding the initiation or discontinuation of statins in patients with NYHA class II-IV ischemic systolic heart failure or in patients on maintenance hemodialysis.
- a 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.
b Contraindications, warnings, and precautions are defined for each statin according to the manufacturer’s prescribing information.
c Individuals with secondary causes of hyperlipidemia were excluded from RCTs reviewed. A triglyceride level ≥500 mg/dL was an exclusion criterion for almost all RCTs. Therefore, ruling out secondary causes is necessary to avoid inappropriate statin therapy.
d No RCTs included only individuals with LDL-C ≥190 mg/dL. However, many trials did include individuals with LDL-C ≥190 mg/dL and all of these trials consistently demonstrated a reduction in ASCVD events. In addition, the CTT meta-analyses have shown that each 39 mg/dL reduction in LDL-C with statin therapy reduced ASCVD events by 22%, and the relative reductions in ASCVD events were consistent across the range of LDL-C levels. Therefore, individuals with primary LDL-C ≥190 mg/dL should be treated with statin therapy.
e 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.
f 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 in a first degree male relative or <65 years in a first degree female relative; high sensitivity-C-reactive protein ≥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 the future.