During the American Heart Association (AHA)’s scientific sessions held in November 2018, the new ultisociety Guideline on the Management of Blood Cholesterol1 was presented to the cardiology community emphasizing some previous key recommendations and new concepts in atherosclerotic cardiovascular disease (ASCVD) prevention. The main updates of these guidelines are:

a new 10-y risk ASCVD categorization for adults 40 to 75 years of age and a lifetime risk estimation in young patients;

A healthy lifestyle including an anti-atherogenic diet, physical activity, weight control and not smoking remains the cornerstone for cardiovascular prevention. Regardless of pharmacological treatment used, these habits are important at all ages, and are some of the key recommendations for ASCVD prevention.

About the treatment with lipid-lowering drugs, statins remain as the first-choice agents. However, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have gained attention as add-on drugs in a more aggressive approach for low-density lipoprotein cholesterol (LDL-c) reduction. Ezetimibe, a cholesterol absorption inhibitor, is the most commonly used drug in combination with statins, contributing for an additional 15-30% reduction in LDL-c levels.

Considerable changes have been made in lipid-lowering therapy with the use of monoclonal antibodies that inhibit PCSK9, such as evolocumab and alirocumab. Based on studies showing an 1.5% absolute risk reduction in composite ASCVD outcomes in a follow-up of 2.2-2.8 years, these new drugs are now recommended and should be included to therapy if lipid targets are not met after maximally tolerated doses of statin and ezetimibe. Recommendations are detailed below:

- Established ASCVD: high-intensity statin should be indicated aiming at a ≥ 50% LDL-c reduction (and LDL-c < 70 mg/dl in those at very high ASCVD risk - Table 1). If this target is not achieved, ezetimibe should be added followed by PSCK9 inhibitors. The rationale is based on the findings that support the safety of extremely low LDL levels, and that, for LDL-c levels, “lower is better”.2

Table 1

Major ASCVD

ACS within the past 12 months

History of MI (other than recent ACS event listed above)

History of ischemic stroke

Symptomatic peripheral arterial disease

High-Risk Conditions

Age ≥ 65 y

Heterozygous familial hypercholesterolemia

History of prior coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD event(s)

Diabetes mellitus

Hypertension

CKD (eGFR 15-59 mL/min/1.73 m2)

Current smoking

Persistently elevated LDL-C (LDL-C ≥100 mg/dl) despite maximally tolerated statin therapy and ezetimibe

History of congestive HF

ABI: indicates ankle-brachial index; ACS: acute coronary syndrome; ASCVD: atherosclerotic cardiovascular disease; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate; HF: heart failure; LDL: low-density lipoprotein cholesterol; and MI, myocardial infarction.

These updated recommendations highlight a more personalized approach, with a follow-up of lipid profile for up to 20 years-old, with reassessment every 4-6 years. If pharmacological therapy is implemented, a closer follow-up is recommended to check LDL-c levels, safety and adherence. Regarding young adults (20 to 39 years of age), it is crucial to exclude secondary causes of hypercholesterolemia, as hypothyroidism (TSH), obstructive liver disease, renal disease and nephrosis, as well as dietary and medication-related dyslipidemia. Also, as mentioned before, intensive lifestyle change is strongly indicated due to its potential to reduce ASCVD risk. For young adults with persistent hypercholesterolemia (LDL-c levels above 160-189 mg/dL), it is recommended to consider risk-enhancing factors in the decision on whether to prescribe statins. For all patients with LDL-c ≥ 190 mg/dl, treatment should be conducted as previously described in “severe hypercholesterolemia” section.

Lifestyle therapies are also pivotal in the management of children and adolescents with abnormal lipid values, aiming to treat obesity and other ASCVD risk factors. Also, this helps to identify individuals who would clearly benefit from statins,6 especially among those with persistent LDL-c ≥ 190 mg/dl (or LDL-c ≥ 160 mg/dl with familial hypercholesterolemia). Due to the very early atherogenic process in familial hypercholesterolemia, children and adolescents with a family history of early ASCVD or severe hypercholesterolemia should be evaluated for lipid profile as early as age of 2 years. Once hypercholesterolemia is detected, a comprehensive family screening is recommended to detect familial forms of hypercholesterolemia.

In conclusion, even though the clinical risk stratification followed by selective use of preventative pharmacological interventions is still the main strategy of primary prevention, these new guidelines allow individualization of treatment by complementary risk stratification, new therapies and facilitation of patient involvement in a shared decision making process.