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 5)

RecommendationsNHLBI GradeNHLBI Evidence StatementsACC/AHA CORACC/AHA LOE
Treatment Targets
  • 1. The Expert Panel makes no recommendations for or against specific LDL-C or non–HDL-C targets for the primary or secondary prevention of ASCVD.

N (No recommendation)1–4
Secondary Prevention
  • 1. 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.

A (Strong)1,6–8,10–23,26–28IA
  • 2. 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 (Table 8 for Safety of Statins, Recommendation 1).

A (Strong)13–22,24,27,28IA
  • 3. 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 and 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.

E (Expert Opinion)IIaB (16,20–43)
Primary Prevention in Individuals ≥21 Years of Age With LDL-C ≥190 mg/dL
  • 1. Individuals with LDL-C ≥190 mg/dL or triglycerides ≥500 mg/dL should be evaluated for secondary causes of hyperlipidemia (Table 6).

B (Moderate)75IB (44,45)
  • 2. 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):

    • Use high-intensity statin therapy unless contraindicated.

    • For individuals unable to tolerate high-intensity statin therapy, use the maximum tolerated statin intensity.

B (Moderate)6,19,28,33–35,37,38I§B
  • 3. 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.

E (Expert Opinion)IIaB (20,46–50)
  • 4. 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, and drug–drug interactions, and consider patient preferences.

E (Expert Opinion)IIbC (51)
Primary Prevention in Individuals With Diabetes and LDL-C 70–189 mg/dL
  • 1. Moderate-intensity statin therapy should be initiated or continued for adults 40–75 years of age with diabetes.

A (Strong)19,29–34,40IA
  • 2. High-intensity statin therapy is reasonable for adults 40–75 years of age with diabetes with a ≥7.5% estimated 10-year ASCVD risk unless contraindicated.

E (Expert Opinion)IIaB (49,52)
  • 3. In adults with diabetes, who are <40 years of age or >75 years of age, or with LDL <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.

E (Expert Opinion)IIaC (53–62)
Primary Prevention in Individuals Without Diabetes and With LDL-C 70–189 mg/dL
  • 1. The Pooled Cohort Equations should be used to estimate 10-year ASCVD risk for individuals with LDL-C 70–189 mg/dL without clinical ASCVD to guide initiation of statin therapy for the primary prevention of ASCVD.

E (Expert Opinion)IB (11)
  • 2. Adults 40–75 years of age with LDL-C 70–189 mg/dL, without clinical ASCVD or diabetes, and with an estimated 10-year ASCVD risk ≥7.5% should be treated with moderate- to high-intensity statin therapy.

A (Strong)28,34–36,38,42–44,47,49–56,76IA
  • 3. 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 ASCVD or diabetes, and with an estimated 10-year ASCVD risk of 5% to <7.5%.

C (Weak)28,34–36,38,42–44,47,49–56,76IIaB
  • 4. Before initiation of 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 that considers the potential for ASCVD risk-reduction benefits and for adverse effects and drug–drug interactions, as well as patient preferences for treatment.

E (Expert Opinion)IIaC (63)
  • 5. 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 evaluation of the potential for ASCVD risk-reduction benefits, adverse effects, and drug–drug interactions and consider patient preferences.

E (Expert Opinion)IIbC (11,13)
Heart Failure and Hemodialysis
  • 1. 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.

N (No Recommendation)71,72

ABI indicates ankle-brachial index; ACC, American College of Cardiology; AHA, American Heart Association; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; COR, Class of Recommendation; HDL-C, high-density lipoprotein cholesterol; 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; TIA, transient ischemic attack; and —, not applicable.

  • 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.

  • Contraindications, warnings, and precautions are defined for each statin according to the manufacturer’s prescribing information (64–70).

  • 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.

  • § 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 Cholesterol Treatment Trialists 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.

  • Estimated 10-year or “hard” ASCVD risk includes first occurrence of nonfatal MI, coronary heart disease 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; 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 might aid in individual risk assessment could be identified in the future.