Treatment algorithm

Your Organizational Guidance

ebpracticenet urges you to prioritize the following organizational guidance:

Évaluation du risque cardiovasculaire en première lignePublished by: Domus MedicaLast published: 2010Cardiovasculaire risicobepaling in de eerste lijnPublished by: Domus MedicaLast published: 2020Globaal Cardiovasculair RisicobeheerPublished by: Domus MedicaLast published: 2007Gestion globale des risques cardiovasculairesPublished by: Domus MedicaLast published: 2007Évaluation du risque cardiovasculaire en première lignePublished by: Domus MedicaLast published: 2020

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

with clinical ASCVD: very high risk

1st line – high-intensity statin

Back
ACUTE
|
with clinical ASCVD: very high risk
1st line – 

high-intensity statin

Patients at very high risk of future atherosclerotic cardiovascular disease (ASCVD) events include those with a history of multiple major ASCVD events (myocardial infarction, acute coronary syndrome within 12 months, ischemic stroke, or symptomatic peripheral arterial disease) or one major ASCVD event and multiple high-risk conditions (age ≥65 years, heterozygous familial hypercholesterolemia, prior coronary artery bypass surgery or percutaneous coronary intervention, diabetes mellitus, hypertension, chronic kidney disease [estimated GFR 15-59 mL/min/1.73 m²], current smoking, congestive heart failure, or persistently elevated LDL-cholesterol ≥100 mg/dL despite maximally tolerated statin therapy and ezetimibe).[44]

If high-intensity statin therapy is contraindicated or associated with significant adverse effects, use maximally tolerated statin therapy.

Primary options

atorvastatin: 40-80 mg orally once daily

OR

rosuvastatin: 20-40 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
with clinical ASCVD: very high risk
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

Consider – ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Back
ACUTE
|
with clinical ASCVD: very high risk
|
on maximally tolerated statin therapy and <50% reduction in LDL-C and/or LDL-C ≥55 mg/dL or non-HDL-C ≥85 mg/dL
Consider – 

ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

For patients with clinical atherosclerotic cardiovascular disease (ASCVD) at very high risk and receiving maximally tolerated statin therapy for secondary prevention but who do not achieve target low-density lipoprotein cholesterol (LDL-C) lowering, consider the addition of ezetimibe or a PCSK9 inhibitor (e.g., alirocumab, evolocumab) or both.[44][56]​​

The decision to add nonstatin therapies should be shared between patient and clinician after a discussion on risks, benefits, and patient preferences. Lifestyle modifications should be optimized, in addition to reviewing adherence to statins.[56]

The threshold for considering additional nonstatin therapy varies depending on risk. If target LDL-C lowering is not achieved with maximally tolerated statin therapy, ezetimibe, and a PCSK9 inhibitor (monoclonal antibody), additional nonstatin therapies are approved and may be considered (e.g., bempedoic acid, inclisiran); however, they may not yet be included in guidelines and you should consult your local protocols.​[56]​​​ See Emerging treatments for more information.  

Primary options

ezetimibe: 10 mg orally once daily

OR

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

Secondary options

ezetimibe: 10 mg orally once daily

-- AND --

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

or

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

with clinical ASCVD: not very high risk and age ≤75 years

1st line – high- or moderate-intensity statin

Back
ACUTE
|
with clinical ASCVD: not very high risk and age ≤75 years
1st line – 

high- or moderate-intensity statin

Patients who are ages ≤75 years and not at very high risk of future atherosclerotic cardiovascular disease (ASCVD) events may be treated with high-intensity statin therapy, or with moderate-intensity statin therapy if high-intensity statin therapy is contraindicated or associated with significant adverse effects.[44]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

Secondary options

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
with clinical ASCVD: not very high risk and age ≤75 years
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

Consider – ezetimibe

Back
ACUTE
|
with clinical ASCVD: not very high risk and age ≤75 years
|
on maximally tolerated statin therapy and <50% reduction in LDL-C and/or LDL-C ≥70 mg/dL (or non-HDL-C ≥100 mg/dL)
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

Ezetimibe may be added to maximally tolerated statin therapy when the LDL-cholesterol level remains ≥70 mg/dL.[44][56]

Primary options

ezetimibe: 10 mg orally once daily

Consider – proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Back
ACUTE
|
with clinical ASCVD: not very high risk and age ≤75 years
|
on maximally tolerated statin and ezetimibe therapy and <50% reduction in LDL-C and/or LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL
Consider – 

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

A PCSK9 inhibitor (e.g., alirocumab, evolocumab) may be added to maximally tolerated statin and ezetimibe therapy when the LDL-cholesterol level remains ≥70 mg/dL or non-HDL-cholesterol remains ≥100 mg/dL.[44][56]​​

The decision to add nonstatin therapies should be shared between patient and clinician after a discussion on risks, benefits, and patient preferences. Lifestyle modifications should be optimized, in addition to reviewing adherence to statins.[56]

The threshold for considering additional nonstatin therapy varies depending on risk. If target low-density lipoprotein cholesterol lowering is not achieved with maximally tolerated statin therapy, ezetimibe, and a PCSK9 inhibitor (monoclonal antibody), additional nonstatin therapies are approved and may be considered (e.g., bempedoic acid, inclisiran); however, they may not yet be included in guidelines and you should consult your local protocols.​[56]​​​ See Emerging treatments for more information.  

Primary options

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

with clinical ASCVD: not very high risk and age >75 years

1st line – high- or moderate-intensity statin

Back
ACUTE
|
with clinical ASCVD: not very high risk and age >75 years
1st line – 

high- or moderate-intensity statin

The decision to initiate high- or moderate-intensity statin therapy in patients >75 years with atherosclerotic cardiovascular disease (ASCVD) should be based on expected benefit versus competing comorbidities.[44]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
with clinical ASCVD: not very high risk and age >75 years
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

without clinical ASCVD: LDL-C ≥190 mg/dL without diabetes mellitus (age 20-75 years)

1st line – high-intensity statin

Back
ACUTE
|
without clinical ASCVD: LDL-C ≥190 mg/dL without diabetes mellitus (age 20-75 years)
1st line – 

high-intensity statin

Patients with LDL-cholesterol ≥190 mg/dL do not require risk assessment for initiation of lipid-lowering therapy.[44]

If high-intensity statin therapy is contraindicated or associated with significant adverse effects, use maximally tolerated statin therapy.

The American Heart Association guideline does not include recommendations for patients with LDL >190 mg/dL who are >75 years; consult a specialist for guidance on how to treat these patients.[44] 

Primary options

atorvastatin: 40-80 mg orally once daily

OR

rosuvastatin: 20-40 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: LDL-C ≥190 mg/dL without diabetes mellitus (age 20-75 years)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

Consider – ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Back
ACUTE
|
without clinical ASCVD: LDL-C ≥190 mg/dL without diabetes mellitus (age 20-75 years)
|
on maximally tolerated statin therapy and <50% reduction in LDL-C and/or LDL-C ≥100 mg/dL (or non-HDL-C ≥130 mg/dL)
Consider – 

ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

In patients ages 20-75 years with baseline LDL-cholesterol (LDL-C) ≥190 mg/dL receiving maximally tolerated statin therapy, if there is a less than 50% reduction in LDL-C and/or LDL-C remains ≥100 mg/dL, consider the addition of ezetimibe or a PCSK9 inhibitor (e.g., alirocumab, evolocumab) or both.[44][56]

The decision to add nonstatin therapies should be shared between patient and clinician after a discussion on risks, benefits, and patient preferences. Lifestyle modifications should be optimized, in addition to reviewing adherence to statins.[56]

The threshold for considering additional nonstatin therapy varies depending on risk. If target LDL-C lowering is not achieved with maximally tolerated statin therapy, ezetimibe, and a PCSK9 inhibitor (monoclonal antibody), additional nonstatin therapies are approved and may be considered (e.g., bempedoic acid, inclisiran); however, they may not yet be included in guidelines and you should consult your local protocols.​[56]​​​ See Emerging treatments for more information.  

Primary options

ezetimibe: 10 mg orally once daily

OR

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

Secondary options

ezetimibe: 10 mg orally once daily

-- AND --

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

or

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

Consider – bile acid sequestrant

Back
ACUTE
|
without clinical ASCVD: LDL-C ≥190 mg/dL without diabetes mellitus (age 20-75 years)
|
on maximally tolerated statin and ezetimibe therapy and <50% reduction in LDL-C, with fasting triglycerides ≤300 mg/dL
Consider – 

bile acid sequestrant

Treatment recommended for SOME patients in selected patient group

In patients ages 20-75 years with baseline LDL-cholesterol (LDL-C) ≥190 mg/dL receiving maximally tolerated statin and ezetimibe therapy, if there is a less than 50% reduction in LDL-C and fasting triglyceride level is ≤300 mg/dL, consider adding a bile acid sequestrant.[44]

Primary options

cholestyramine: 4 g orally once or twice daily initially, adjust dose according to response, maximum 24 g/day

without clinical ASCVD: LDL-C ≥160 mg/dL without diabetes mellitus (age 20-39 years)

1st line – consider high- or moderate-intensity statin

Back
ACUTE
|
without clinical ASCVD: LDL-C ≥160 mg/dL without diabetes mellitus (age 20-39 years)
1st line – 

consider high- or moderate-intensity statin

Statin therapy may be considered in patients ages 20-39 years if there is a family history of premature atherosclerotic cardiovascular disease (ASCVD) and LDL-cholesterol ≥160 mg/dL.[44] There is a lack of data about whether high- or moderate-intensity statin therapy is preferred in these patients; therefore, physicians should make a decision on an individual basis. 

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: LDL-C ≥160 mg/dL without diabetes mellitus (age 20-39 years)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)

1st line – risk discussion + lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
low 10-year ASCVD risk (<5%)
1st line – 

risk discussion + lifestyle modifications

In patients with a low risk of 10-year atherosclerotic cardiovascular disease (ASCVD) (<5%) have a risk discussion and advise of lifestyle changes to reduce potential risk.[44]

There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.[30]​​[64][65][66]​​

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

1st line – risk discussion + lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
borderline 10-year ASCVD risk (5% to <7.5%)
1st line – 

risk discussion + lifestyle modifications

In patients with a borderline risk of 10-year atherosclerotic cardiovascular disease (ASCVD) (5% to <7.5%) have a risk discussion and advise of lifestyle changes to reduce potential risk.[44]

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

Consider – moderate-intensity statin

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
borderline 10-year ASCVD risk (5% to <7.5%)
Consider – 

moderate-intensity statin

Treatment recommended for SOME patients in selected patient group

Moderate-intensity statin therapy may be considered after a clinician-patient discussion in patients with a borderline risk of 10-year atherosclerotic cardiovascular disease (ASCVD) (5% to <7.5%). Risk enhancers include: family history of premature ASCVD; persistently elevated LDL-cholesterol ≥160 mg/dL or non-HDL-cholesterol ≥190 mg/dL; chronic kidney disease (estimated GFR 15-59 mL/min/1.73 m²); metabolic syndrome; preeclampsia, premature menopause; inflammatory diseases (especially rheumatoid arthritis, psoriasis, HIV); high-risk ethnicity (e.g., South Asian ancestry); elevated lipid/biomarkers (high-sensitivity CRP ≥2 mg/L; lipoprotein(a) >50 mg/dL or >125 nmol/L; apolipoprotein B ≥130 mg/dL); ankle brachial index <0.9.[44]

If the decision about statin therapy remains uncertain, consider coronary artery calcium (CAC) testing. If CAC is 0, statin therapy can be withheld and the patient reassessed in 5-10 years if there is no high-risk condition (diabetes, family history of premature ASCVD, or tobacco smoking). Statin therapy should be considered if CAC is ≥100 or in ≥75th percentile for age/sex/ethnicity, or if CAC is 1-99 and patient is age ≥55 years.[44]

Patients who do not achieve target low-density lipoprotein cholesterol (LDL-C) reduction on a moderate-intensity statin may be considered for a switch to a high-intensity statin (see below). CAC score can also be used to aid decision to switch to a high-intensity statin or to consider nonstatin options (ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor monoclonal antibody) if LDL-C targets are not met.[56]

Primary options

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

1st line – moderate-intensity statin

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
intermediate 10-year ASCVD risk (≥7.5% to <20%)
1st line – 

moderate-intensity statin

Moderate-intensity statin therapy may be considered after a clinician-patient discussion in patients with an intermediate risk of 10-year atherosclerotic cardiovascular disease (ASCVD) (≥7.5% to <20%). Risk enhancers include: family history of premature ASCVD; persistently elevated LDL-cholesterol ≥160 mg/dL or non-HDL-cholesterol ≥190 mg/dL; chronic kidney disease (estimated GFR 15-59 mL/min/1.73 m²); metabolic syndrome; preeclampsia, premature menopause; inflammatory diseases (especially rheumatoid arthritis, psoriasis, HIV); high-risk ethnicity (e.g., South Asian ancestry); elevated lipid/biomarkers (high-sensitivity CRP ≥2 mg/L; lipoprotein(a) >50 mg/dL or >125 nmol/L; apolipoprotein B ≥130 mg/dL); ankle brachial index <0.9.[44]

If the decision about statin therapy remains uncertain, consider coronary artery calcium (CAC) testing. If CAC is 0, statin therapy can be withheld and the patient reassessed in 5-10 years if there is no high-risk condition (diabetes, family history of premature ASCVD, or tobacco smoking). Statin therapy should be considered if CAC is ≥100 or in ≥75th percentile for age/sex/ethnicity, or if CAC is 1-99 and patient is age ≥55 years.[44]

Patients who do not achieve target low-density lipoprotein cholesterol (LDL-C) reduction on a moderate-intensity statin may be considered for a switch to a high-intensity statin (see below). CAC score can also be used to aid decision to switch to a high-intensity statin or to consider nonstatin options (ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor monoclonal antibody) if LDL-C targets are not met.[56]

Primary options

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
intermediate 10-year ASCVD risk (≥7.5% to <20%)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

1st line – high-intensity statin

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
high 10-year ASCVD risk (≥20%)
1st line – 

high-intensity statin

High-intensity statin therapy is recommended after a clinician-patient discussion in patients with a high risk of 10-year atherosclerotic cardiovascular disease (ASCVD) (≥20%).[44]

If high-intensity statin therapy is contraindicated or associated with significant adverse effects, use maximally tolerated statin therapy.

Primary options

atorvastatin: 40-80 mg orally once daily

OR

rosuvastatin: 20-40 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
high 10-year ASCVD risk (≥20%)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

Consider – ezetimibe

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
|
high 10-year ASCVD risk (≥20%)
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

For patients with high 10-year atherosclerotic cardiovascular disease (ASCVD) risk (≥20%), and who achieve LDL-cholesterol (LDL-C) reduction <50% and/or LDL-C ≥70 mg/dL (or non-HDL-C ≥ 100 mg/dL) on maximally tolerated statin therapy, addition of ezetimibe may be considered.[44][56]

Primary options

ezetimibe: 10 mg orally once daily

without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age >75 years)

1st line – consider moderate-intensity statin

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age >75 years)
1st line – 

consider moderate-intensity statin

Moderate-intensity statin therapy may be considered in patients ages >75 years with LDL-cholesterol (LDL-C) 70-189 mg/dL.[44]

Consider stopping statin therapy in patients >75 years old with physical or cognitive decline, multimorbidity, frailty, or reduced life expectancy that may limit the benefits of statin therapy.

In adults ages 76-80 years with an LDL-C 70-189 mg/dL, consider coronary artery calcium testing to assess the need for statin therapy.

Primary options

atorvastatin: 10-20 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

pravastatin: 40-80 mg orally once daily

OR

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age >75 years)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

without clinical ASCVD: with diabetes mellitus and risk enhancers (age 20-39 years)

1st line – consider moderate-intensity statin

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus and risk enhancers (age 20-39 years)
1st line – 

consider moderate-intensity statin

Adults ages 20-39 years are generally at low 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and there is limited information on whether statins are beneficial in patients of this age who have diabetes. However, moderate-intensity statin therapy may be considered after a clinician-patient discussion in patients ages 20-39 years who have diabetes and additional risk enhancers.[44]

Diabetes-specific risk enhancers include: long duration of diabetes (≥10 years of type 2 diabetes mellitus or ≥20 years of type 1 diabetes mellitus); albuminuria (≥30 mcg/mg of creatinine); estimated GFR <60 mL/min/1.73m²; retinopathy; neuropathy; ankle brachial index <0.9.[44]

Primary options

atorvastatin: 10-20 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

pravastatin: 40-80 mg orally once daily

OR

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus and risk enhancers (age 20-39 years)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk <7.5% and no risk factors (age 40-75 years)

1st line – moderate-intensity statin

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk <7.5% and no risk factors (age 40-75 years)
1st line – 

moderate-intensity statin

Moderate-intensity statin therapy is indicated in adults ages 40-75 years with diabetes who have an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk of <7.5% and no additional high risk factors.[44][56]

Primary options

atorvastatin: 10-20 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

pravastatin: 40-80 mg orally once daily

OR

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk <7.5% and no risk factors (age 40-75 years)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

Consider – switch to high-intensity statin

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk <7.5% and no risk factors (age 40-75 years)
|
LDL-C reduction <30%-49% and/or LDL-C ≥100 mg/dL (or non-HDL-C ≥130 mg/dL) on moderate-intensity statin
Consider – 

switch to high-intensity statin

Treatment recommended for SOME patients in selected patient group

For patients with 10-year atherosclerotic cardiovascular disease (ASCVD) <7.5% who achieve LDL-cholesterol (LDL-C) reduction <30%-49% and/or LDL-C ≥100 mg/dL (or non-HDL-C ≥130 mg/dL) on moderate-intensity statin therapy, switching to high-intensity statin therapy may be considered.[44][56]

If target LDL-C lowering is not achieved with maximally tolerated statin therapy, additional nonstatin therapies may be considered; consult your local protocols.[56]

Primary options

atorvastatin: 40-80 mg orally once daily

OR

rosuvastatin: 20-40 mg orally once daily

without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk ≥7.5% and risk enhancers (age 40-75 years)

1st line – high-intensity statin

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk ≥7.5% and risk enhancers (age 40-75 years)
1st line – 

high-intensity statin

High-intensity statin therapy is indicated in adults ages 40-75 years with diabetes who have an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk of ≥7.5% and high risk factors.[44][56]​​

Diabetes-specific risk enhancers include: long duration of diabetes (≥10 years of type 2 diabetes mellitus or ≥20 years of type 1 diabetes mellitus); albuminuria (≥30 mcg/mg of creatinine); estimated GFR <60 mL/min/1.73m²; retinopathy; neuropathy; ankle brachial index<0.9.[44]

If high-intensity statin therapy is contraindicated or associated with significant adverse effects, use maximally tolerated statin therapy.

Primary options

atorvastatin: 40-80 mg orally once daily

OR

rosuvastatin: 20-40 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk ≥7.5% and risk enhancers (age 40-75 years)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

Consider – ezetimibe

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk ≥7.5% and risk enhancers (age 40-75 years)
|
10-year ASCVD predicted risk ≥20%, LDL-C reduction <50% and/or LDL-C ≥70 mg/dL (or non-HDL-C ≥100 mg/dL) on maximally tolerated statin therapy
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

In adult patients with diabetes and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥20%, consider adding ezetimibe to maximally tolerated statin therapy to reduce LDL-cholesterol levels to ≥50%.[44]

Primary options

ezetimibe: 10 mg orally once daily

without clinical ASCVD: with diabetes mellitus (age >75 years)

1st line – consider moderate-intensity statin therapy

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus (age >75 years)
1st line – 

consider moderate-intensity statin therapy

Statin therapy may be considered after a clinician-patient discussion in patients with diabetes ages >75 years.[44] Moderate-intensity statin therapy is considered a reasonable option in these patients. 

Primary options

atorvastatin: 10-20 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

pravastatin: 40-80 mg orally once daily

OR

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

pitavastatin: 1-4 mg orally once daily

Plus – lifestyle modifications

Back
ACUTE
|
without clinical ASCVD: with diabetes mellitus (age >75 years)
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Lifestyle changes are recommended for all patients. There is clear evidence that dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise, and the addition of plant stanols/sterols to the diet leads to a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol.​[30][64][65][66]

The implementation of dietary change can be difficult for many patients, and it may be helpful to involve a dietician in the patient's care. A reduced intake of cholesterol and saturated fats should be advised, as well as increased consumption of dietary fiber, complex carbohydrates, and unsaturated fats.[14][31]​​ 

Aerobic exercise plus dietary modification has been shown to lead to significant reductions in LDL-C compared with no lifestyle changes or diet alone.[71]

ONGOING

familial hypercholesterolemia

1st line – specialist consultation

Back
ONGOING
|
familial hypercholesterolemia
1st line – 

specialist consultation

Familial hypercholesterolemia (FH) requires specialist consultation. 

Consider formal evaluation for FH and/or referral to lipid clinic in patients with LDL-cholesterol (LDL-C) ≥190 mg/dL, physical findings of FH (tendinous xanthomata, arcus cornealis <45 years old), or a personal or family history of premature atherosclerotic cardiovascular disease with LDL-C ≥155 mg/dL. For patients on lipid-lowering therapy, consider pretherapy LDL-C and, if not available, estimate pretherapy LDL-C levels based on expected reduction in LDL-C from lipid-lowering agents.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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