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.

• 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)

• 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)

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.

• 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).

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.

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.

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.

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)

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.

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)

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.

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

• 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.

• 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

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.

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 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

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.