Recommendations were made after a careful search of the medical literature and review of the evidence. The strength of the recommendation was based on several things: the certainty or confidence in the evidence, different patient values and preferences, and the balance of desirable and undesirable effects. For this guideline, desirable effects included lower risk of heart disease events and undesirable effects included the number of people stopping the medications because of side effects.

Overall, only small benefits were observed in some of the outcomes and the confidence for the evidence was low or moderate leading to conditional recommendations for treatment options based on shared decision-making with patients.

• In adults who have elevated LDL-C (cholesterol) and heart disease or are at increased risk for heart disease:
  • AACE suggests adding alirocumab or evolocumab to usual care if not at goal LDL-C
    Conditional recommendation | Moderate certainty of evidence
  • AACE suggests the use of bempedoic acid in addition to usual care if statin intolerant
    Conditional recommendation | Moderate certainty of evidence
  • No recommendation for or against use of inclisiran
    No recommendation | Insufficient evidence
  • AACE suggests treating to a goal of less than 70 mg/dL LDL-C
    Conditional recommendation | Low certainty of evidence

• In adults who have elevated LDL-C (cholesterol) without heart disease and can tolerate other lipid-lowering medications:
  • AACE suggests against the use of alirocumab, evolocumab, or bempedoic acid
    Conditional recommendation | Moderate certainty of evidence

• In adults who have elevated triglycerides and heart disease or are at increased risk for heart disease:
  • AACE suggests the use of EPA in addition to usual care
    Conditional recommendation | Low certainty of evidence
  • AACE suggests against the use of EPA+DHA
    Conditional recommendation | Low certainty of evidence
  • AACE recommends against the use of niacin
    Strong recommendation | Low certainty of evidence

• To better understand your risk of heart disease, your health care professional will ask about your medical history and order some routine blood tests.
• Your doctor should calculate your risk using a specific calculator to determine your risk for future heart disease events.
• Your doctor may recommend additional tests measuring other types of lipids (ApoB or Lp[a]) or imaging for calcium buildup in the arteries of your heart (also called coronary artery calcium); however, evidence does not support use of these tests in most people as they do not provide substantial improvement in the calculation of risk for heart disease.

• Shared decision-making means that you and your health care professional make decisions about your care together, based on your values and preferences, your doctor’s experience, and evidence-based information.⁴
• These recommendations can support shared decision-making discussions with your health care professional to determine the right medication for you and to understand your risk of developing heart disease.
• This approach will be especially helpful when there is more than one option for screening, testing, or treatment, and no option has a clear advantage. It is also important when the possible benefits and harms of each option may affect a person differently.
• The sections below show how different treatments affect the risk of different outcomes. The potential risks are shown as the number of people experiencing that outcome per 1,000 individuals based on information from clinical trials. Talking about the difference risk of each outcome with your health care professional can help you decide on a treatment.

• Alirocumab and evolocumab are injectable medications that probably provide a small decrease in the risk for heart attack with minimal side effects (injection site reactions). However, the costs of these treatments can be high and vary depending on insurance coverage. See Table 1 for more information on outcomes.
• At this time, there is not enough information from clinical trials on patient-important outcomes to make a recommendation for or against using inclisiran. However, for some people with very high cholesterol, inclisiran may be an option if they can afford the treatment and have access to receive it in a health care setting. Potential side effects with use of inclisiran included injection site reactions, lung infections, and joint pain.
• Bempedoic acid may be an option for people who have side effects with statins, as it probably provides a small decrease in risk of heart attack and a trivial decrease in limb ischemia and amputation (see Table 1). However, there can be side effects with this medication, including skin flushing (redness and heat) and stomach and intestinal issues. Studies reported a moderate increase in the number of people who stopped taking bempedoic acid due to side effects compared with those taking evolocumab and alirocumab.
• Different types and amounts of omega-3 fatty acids (fish oil) are available by prescription. EPA alone (icosapent ethyl) may result in a small decrease in the risk of heart attacks but can also increase the risk of certain adverse events like bleeding and heart arrythmia (irregular heartbeat).
• The combination of EPA+DHA and niacin were not observed to provide a reduction in cardiovascular events but may increase the numbers of people stopping treatment due to side effects. Similar to EPA alone, the combination of EPA+DHA can increase the risk of an irregular heartbeat (arrythmia) and bleeding along with impaired taste and indigestion.
• Niacin is not recommended to reduce the risk of heart disease as it may not lower the risk of heart disease and death and probably increases the risk of hospitalization due to high blood sugar in people with diabetes, higher rates of infection, and bleeding. There is currently no information on the use of niacin in people with extremely high levels of triglycerides or in preventing pancreatitis.

• There is limited information to set a specific goal for cholesterol level with treatment.
• However, it is important to lower your cholesterol if it is really high (greater than 130 mg/dL for most people and greater than 70 mg/dL for people with heart disease). Many studies have shown that lowering cholesterol from above 100 mg/dL to below 100 mg/dL decreases a person’s risk of future heart disease.
• When comparing patients who reached different cholesterol (LDL-C) levels after taking medications, people whose cholesterol was less than 70 mg/dL had a small decrease in the risk of heart attack and a trivial or slight decrease in the risk of death (see Table 2).
• There is not enough information on patient-important outcomes to support a goal of less than 55 mg/dL LDL-C for most people.