ACC/AHA 2018 Cholesterol Guidelines

Familial Hypercholesterolemia (FH) is very high risk. If you have FH, early diagnosis and treatment to lower low-density lipoprotein cholesterol (LDL-C) are important to reduce the risk for ASCVD, including heart attack, angina, stent, bypass, stroke, or peripheral artery disease for men, women, and children.

Prevention starts in childhood. Get your children and all first, second, and third degree relatives’ cholesterol checked.

Manage all of your risk factors and risk-enhancing factors.

Get your LDL-C down early and keep it there.

Take a high intensity statin if you can.

Try to get your LDL-C below 100 mg/dL if you don’t have ASCVD or below 70 mg/dL if you do have ASCVD.

Add ezetimibe to get your LDL-C below your treatment threshold.

If that’s not enough, consider adding a PCSK9 inhibitor[2][3].

Check your LDL-C 4-12 weeks after you start a treatment or change a dose to see what your response is to the therapy.

Keep taking your medication as prescribed. Talk to your medical care team if you have side effects or if you have questions.

The good news is, you can lower your risk for heart attack, angina, stent, bypass, stroke, or peripheral artery disease.

Everything Starts with a Heart-Healthy Lifestyle.
A heart-healthy diet[4] and regular exercise[5] throughout a lifetime are the cornerstones of any approach to lower risk for ASCVD and can reduce risk at all ages.

Cholesterol Matters.
The guideline clearly states that high blood cholesterol, particularly Low-Density Lipoprotein Cholesterol (LDL-C), is a “primary cause of atherosclerosis,” and that “adult populations with [an LDL-C level of about 100 mg/dL] manifest low rates of ASCVD.”

Other Risk Factors Matter Too.
Cholesterol is not the only risk factor for cardiovascular disease. Other major risk factors include: cigarette smoking, hypertension, dysglycemia, other lipoprotein abnormalities, and age. There are other important “risk-enhancing” factors[6]. The more risk factors you have, the greater your risk for ASCVD, so it is important to address all risk factors whenever possible.

FH is Very High Risk.
FH falls under “severe primary hypercholesterolemia” (LDL-C level ≥ 190 mg/dL) and is in a category with the highest overall risk, along with secondary ASCVD prevention. There is no need to use a risk calculator for people with FH. FH treatment should begin early.

Treatment Works.
“Randomized Controlled Trials of cholesterol-lowering drugs in high-risk patients confirm that LDL-C lowering produces marked reductions in ASCVD.” “Those with very high LDL-C values are most likely to achieve the greatest benefit from evidence-based LDL-C-lowering therapy.” “The greatest absolute benefit accrues to patients with the highest baseline LDL-C levels.”

Statins are First Line Treatment.
For people with LDL ≥ 190 mg/dL, high intensity statin is recommended[7]. If a person with FH cannot take a high intensity statin, then a maximally tolerated statin is recommended. The goal of statin therapy for those with FH (and other severe hypercholesterolemias) is to achieve at least a 50% reduction in LDL-C or achieve an LDL-C below the threshold of 70 mg/dL for those with ASCVD or below 100 mg/dL for those without ASCVD.

LDL-C Threshold for Secondary ASCVD Prevention: 70 mg/dL.
The goal of secondary prevention is to try to detect a disease and prevent it from getting worse. If a person under age 75, with LDL ≥ 190 mg/dL who already has ASCVD, cannot achieve an LDL-C of less than 70 mg/dL on a high intensity statin or maximally tolerated statin, it is reasonable to add ezetimibe. If the patient still has an LDL-C above 70 mg/dL and is “judged to be very high risk”[8], it is reasonable to add a PCSK9 inhibitor to the statin plus ezetimibe therapy.

LDL-C Threshold for Primary Prevention: 100 mg/dL.
The goal of primary prevention is to prevent the onset of disease. If a person age 20 – 75, with LDL ≥ 190 mg/dL who does not have ASCVD cannot achieve an LDL-C below 100 mg/dL on a high intensity statin or maximally tolerated statin, it is reasonable to add ezetimibe. The guideline also says bile acid sequestrants may be considered if statin plus ezetimibe treatment results in a less than 50% reduction in LDL-C in a person with a baseline LDL-C of ≥ 190 mg/dL, as long as fasting triglycerides are ≤ 300 mg/dL[9].

PCSK9 Inhibitors for Primary Prevention.
The Guideline states that the addition of a PCSK9 inhibitor may be considered for patients age 30 – 75 years specifically with heterozygous FH who cannot achieve an LDL-C below 100 mg/dL on statin and ezetimibe. A PCSK9 inhibitor may also be considered for patients age 40 – 75 years with baseline LDL-C ≥ 220 mg/dL whose LDL-C is ≥ 130 mg/dL on maximally tolerated statin and ezetimibe therapy.

Statin-Associated Side Effects.
Statins are “usually well tolerated and safe.” However, statin associated side effects are observed in 5-20% of patients, posing a challenge for adherence to therapy. The guideline recommends rechallenging with a modified dosing regimen or an alternate statin for patients who experience statin-associated side effects. For patients with severe symptoms or recurrent symptoms, it is reasonable to use nonstatin therapies to lower LDL-C in patients at increased risk for ASCVD.

Repeat Lipid Measurements to Assess Adherence and Response to Treatment.
Lipid testing is recommended 4-12 weeks after statin initiation or dose adjustment, and repeated every 3-12 months, as needed.

Prevention Starts in Childhood.
The guideline states that it is reasonable to test cholesterol levels at age 2 (fasting or nonfasting) if there is a family history of high cholesterol and/or early cardiovascular disease. It’s recommended that all children have a fasting lipid panel (or non-fasting non HDL-C) between the ages of 9 and 11 and again between 17 and 21. It is reasonable to start statin therapy in children and adolescents 10 years or older with an LDL-C ≥ 190 mg/dL or ≥ 160 mg/dL with a clinical presentation consistent with FH.

Issues Specific to Women.
“Although atherosclerosis typically occurs later in women than in men, CVD remains the leading cause of death in women. Statins clearly reduce ASCVD events in women as well as men with ASCVD.” This guideline is particularly helpful in that it highlights risk factors specific to women, which have been shown to increase the risk for ASCVD[10]. Women with genetic lipid disorders (such as FH) should consider consulting a clinician with lipid expertise before starting a pregnancy, since both cholesterol and triglycerides go up during all pregnancies. Statins should not be taken during pregnancy and breastfeeding.

Cascade Family Screening for FH.
“Cascade screening in families is highly effective for the identification of family members at risk of ASCVD.”

[1] Atherosclerotic cardiovascular disease (ASCVD) includes acute coronary syndrome (ACS, or heart attack or unstable angina), history of myocardial infarction (MI, or heart attack), stable or unstable angina or coronary or other arterial revascularization (stent or bypass), stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin. Atherosclerotic origin means caused by plaque (fat, cholesterol, calcium and other substances) build up inside the arteries, hardening and narrowing the arteries.

[2] There are gaps in this guideline for people with FH who cannot get their LDL-C down below recommended levels on maximally tolerated statin plus ezetimibe. The guideline does not address the use of PCSK9 inhibitors for people over age 75 years, or under age 30 years for primary prevention.  For a person with FH and ASCVD with no other high-risk conditions, there is no recommendation addressing treatment with PCSK9 inhibitors when the LDL-C is in the 70 – 100 mg/dL range.

[3] The guideline specifically states: “At mid-2018 list prices, PCSK9 inhibitors have a low cost value” and recommend a “clinician-patient discussion about the net benefit, safety, and cost” of a PCSK9 inhibitor before adding this therapy. The list price of PCSK9 inhibitors has since come down substantially, so we will have to see if that changes the “value” determined by the guideline committee. It is important to note that the guideline does not include a determination of value for other non-statin therapies, including ezetimibe and bile acid sequestrants, for which there is less data than for PCSK9 inhibitors, and in the case of bile acid sequestrants especially, the cost to patients can be surprisingly high.

[4] Dietary pattern should emphasize intake of vegetables, fruits, whole grains, legumes, healthy protein sources (low-fat diary products, low-fat poultry, fish/seafood, and nuts), non-tropical vegetable oils. Limit intake of sweets, sugar-sweetened beverages, and red meats.

[5] Moderate to vigorous intensity aerobic physical activity 3-4 sessions per week, lasting an average of 40 minutes per session.

[6] Risk-enhancing factors include: family history of premature ASCVD, persistently elevated LDL-C levels ≥ 160 mg/dL, metabolic syndrome, chronic kidney disease, history of preeclampsia or premature menopause (age < 40 years), chronic inflammatory disorders (rheumatoid arthritis, psoriasis, or chronic HIV), high-risk ethnic groups (South Asians), persistent elevations of triglycerides ≥ 175 mg/dL, apolipprotein B ≥ 130 mg/dL, high-sensitivity C-reactive protein ≥ 2.0 mg/dL, ankle-brachial index < 0.9, and lipoprotein (a) ≥ 50 mg/dL or 125 nmol/L, especially at higher values of lipoprotein (a).

[7] High intensity statins are rosuvastatin (Crestor) 20 or 40 mg or atorvastatin (Lipitor) 40 or 80 mg.

[8] Very high risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. High-risk conditions include: age ≥ 65 years, heterozygous FH, history of bypass or stent outside of the major ASCVD event, diabetes, hypertension, Chronic Kidney Disease, current smoking, persistently elevated LDL-C ≥ 100 mg/dL despite statin plus ezetimibe therapy, or history of congestive heart failure.

[9] “The clinical utility of bile acid sequestrants is limited by the absence of ASCVD outcomes data when used in combination with statins, as well as by the issues of twice-daily dosing, high pill burden, the absence of well-tolerated generic formulations, drug interactions, and the potential for triglyceride elevation.”

[10] Conditions specific to women include: premature menopause (under 40 years), history of pregnancy-related disorders (hypertension, preeclampsia, gestational diabetes, small-for-gestational age infants, preterm deliveries).

Follow a heart-healthy diet and exercise regularly.Familial Hypercholesterolemia (FH) is very high risk. If you have FH, early diagnosis and treatment to lower low-density lipoprotein cholesterol (LDL-C) are important to reduce the risk for ASCVD, including heart attack, angina, stent, bypass, stroke, or peripheral artery disease for men, women, and children.

Prevention starts in childhood. Get your children and all first, second, and third degree relatives’ cholesterol checked.

Manage all of your risk factors and risk-enhancing factors.

Get your LDL-C down early and keep it there.

Take a high intensity statin if you can

Try to get your LDL-C below 100 mg/dL if you don’t have ASCVD or below 70 mg/dL if you do have ASCVD.

Add ezetimibe to get your LDL-C below your treatment threshold.

If that’s not enough, consider adding a PCSK9 inhibitor[2][3].

Check your LDL-C 4-12 weeks after you start a treatment or change a dose to see what your response is to the therapy.

Keep taking your medication as prescribed. Talk to your medical care team if you have side effects or if you have questions.

The good news is, you can lower your risk for heart attack, angina, stent, bypass, stroke, or peripheral artery disease.