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The purpose of this guideline is to provide direction for the management of patients with high blood cholesterol to decrease the incidence of atherosclerotic vascular disease. The update was undertaken because new evidence has emerged since the publication of the 2013 ACC/AHA cholesterol guideline about additional cholesterol-lowering agents including ezetimibe and PCSK9 inhibitors.

Dr. Gregory Palko and Dr. Neil Skolnik of Abington (Pa.) Jefferson Health
Dr. Gregory Palko and Dr. Neil Skolnik

Measurement and therapeutic modalities

In adults aged 20 years and older who are not on lipid-lowering therapy, measurement of a lipid profile is recommended and is an effective way to estimate atherosclerotic cardiovascular disease (ASCVD) risk and documenting baseline LDL-C.

Statin therapy is divided into three categories: High-intensity statin therapy aims for lowering LDL-C levels by more than 50%, moderate-intensity therapy by 30%-49%, and low-intensity therapy by less than 30%.
 

Cholesterol management groups

In all individuals at all ages, emphasizing a heart-healthy lifestyle, meaning appropriate diet and exercise, to decrease the risk of developing ASCVD should be advised.

Individuals fall into groups with distinct risk of ASCVD or recurrence of ASCVD and the recommendations are organized according to these risk groups.

Secondary ASCVD prevention: Patients who already have ASCVD by virtue of having had an event or established diagnosis (MI, angina, cerebrovascular accident, or peripheral vascular disease) fall into the secondary prevention category:

  • Patients aged 75 years and younger with clinical ASCVD: High-intensity statin therapy should be initiated with aim to reduce LDL-C levels by 50%. In patients who experience statin-related side effects, a moderate-intensity statin should be initiated with the aim to reduce LDL-C by 30%-49%.
  • In very high-risk patients with an LDL-C above 70 mg/dL on maximally tolerated statin therapy, it is reasonable to consider the use of a non–statin cholesterol-lowering agent with an LDL-C goal under 70 mg/dL. Ezetimibe (Zetia) can be used initially and if LDL-C remains above 70 mg/dL, then consideration can be given to the addition of a PCSK9-inhibitor therapy (strength of recommendation: ezetimibe – moderate; PCSK9 – strong). The guideline discusses that, even though the evidence supports the efficacy of PCSK9s in reducing the incidence of ASCVD events, the expense of PCSK9 inhibitors give them a high cost, compared with value.
  • For patients more than age 75 years with established ASCVD, it is reasonable to continue high-intensity statin therapy if patient is tolerating treatment.

Severe hypercholesterolemia:

  • Patients with LDL-C above 190 mg/dL do not need a 10-year risk score calculated. These individuals should receive maximally tolerated statin therapy.
  • If patient is unable to achieve 50% reduction in LDL-C and/or have an LDL-C level of 100 mg/dL, the addition of ezetimibe therapy is reasonable.
  • If LDL-C is still greater than 100mg/dL on a statin plus ezetimibe, the addition of a PCSK9 inhibitor may be considered. It should be recognized that the addition of a PCSK9 in this circumstance is classified as a weak recommendation.
 

 

Diabetes mellitus in adults:

  • In patients aged 40-75 years with diabetes, regardless of 10-year ASCVD risk, should be prescribed a moderate-intensity statin (strong recommendation).
  • In adults with diabetes mellitus and multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with goal to reduce LDL-C by more than 50%.
  • In adults with diabetes mellitus and 10-year ASCVD risk of 20% or higher, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce LDL-C levels by 50% or more.
  • In patients aged 20-39 years with diabetes that is either of long duration (at least 10 years, type 2 diabetes mellitus; at least 20 years, type 1 diabetes mellitus), or with end-organ damage including albuminuria, chronic renal insufficiency, retinopathy, neuropathy, or ankle-brachial index below 0.9, it may be reasonable to initiate statin therapy (weak recommendation).

Primary prevention in adults: Adults with LDL 70-189 mg/dL and a 10-year risk of a first ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the pooled cohort equation. Adults should be categorized according to calculated risk of developing ASCVD: low risk (less than 5%), borderline risk (5% to less than 7.5%), intermediate risk (7.5% and higher to less than 20%), and high risk (20% and higher) (strong recommendation:

  • Individualized risk and treatment discussion should be done with clinician and patient.
  • Adults in the intermediate-risk group (7.5% and higher to less than 20%), should be placed on moderate-intensity statin with LDL-C goal reduction of more than 30%; for optimal risk reduction, especially in high-risk patients, an LDL-C reduction of more than 50% (strong recommendation).
  • Risk-enhancing factors can favor initiation of intensification of statin therapy.
  • If a decision about statin therapy is uncertain, consider measuring coronary artery calcium (CAC) levels. If CAC is zero, statin therapy may be withheld or delayed, except those with diabetes as above, smokers, and strong familial hypercholesterolemia with premature ASCVD. If CAC score is 1-99, it is reasonable to initiate statin therapy for patients older than age 55 years; If CAC score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate a statin.

Statin safety: Prior to initiation of a statin, a clinician-patient discussion is recommended detailing ASCVD risk reduction and the potential for side effects/drug interactions. In patients with statin-associated muscle symptoms (SAMS), a detailed account for secondary causes is recommended. In patients with true SAMS, it is recommended to check a creatine kinase level and hepatic function panel; however, routine measurements are not useful. In patients with statin-associated side effects that are not severe, reassess and rechallenge patient to achieve maximal lowering of LDL-C with a modified dosing regimen.
 

The bottom line

Lifestyle modification is important at all ages, with specific population-guided strategies for lowering cholesterol in subgroups as discussed above. Major changes to the AHA/ACC Cholesterol Clinical Practice Guidelines now mention new agents for lowering cholesterol and using CAC levels as predictability scoring.

Reference

Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Nov 10.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Palko is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

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The purpose of this guideline is to provide direction for the management of patients with high blood cholesterol to decrease the incidence of atherosclerotic vascular disease. The update was undertaken because new evidence has emerged since the publication of the 2013 ACC/AHA cholesterol guideline about additional cholesterol-lowering agents including ezetimibe and PCSK9 inhibitors.

Dr. Gregory Palko and Dr. Neil Skolnik of Abington (Pa.) Jefferson Health
Dr. Gregory Palko and Dr. Neil Skolnik

Measurement and therapeutic modalities

In adults aged 20 years and older who are not on lipid-lowering therapy, measurement of a lipid profile is recommended and is an effective way to estimate atherosclerotic cardiovascular disease (ASCVD) risk and documenting baseline LDL-C.

Statin therapy is divided into three categories: High-intensity statin therapy aims for lowering LDL-C levels by more than 50%, moderate-intensity therapy by 30%-49%, and low-intensity therapy by less than 30%.
 

Cholesterol management groups

In all individuals at all ages, emphasizing a heart-healthy lifestyle, meaning appropriate diet and exercise, to decrease the risk of developing ASCVD should be advised.

Individuals fall into groups with distinct risk of ASCVD or recurrence of ASCVD and the recommendations are organized according to these risk groups.

Secondary ASCVD prevention: Patients who already have ASCVD by virtue of having had an event or established diagnosis (MI, angina, cerebrovascular accident, or peripheral vascular disease) fall into the secondary prevention category:

  • Patients aged 75 years and younger with clinical ASCVD: High-intensity statin therapy should be initiated with aim to reduce LDL-C levels by 50%. In patients who experience statin-related side effects, a moderate-intensity statin should be initiated with the aim to reduce LDL-C by 30%-49%.
  • In very high-risk patients with an LDL-C above 70 mg/dL on maximally tolerated statin therapy, it is reasonable to consider the use of a non–statin cholesterol-lowering agent with an LDL-C goal under 70 mg/dL. Ezetimibe (Zetia) can be used initially and if LDL-C remains above 70 mg/dL, then consideration can be given to the addition of a PCSK9-inhibitor therapy (strength of recommendation: ezetimibe – moderate; PCSK9 – strong). The guideline discusses that, even though the evidence supports the efficacy of PCSK9s in reducing the incidence of ASCVD events, the expense of PCSK9 inhibitors give them a high cost, compared with value.
  • For patients more than age 75 years with established ASCVD, it is reasonable to continue high-intensity statin therapy if patient is tolerating treatment.

Severe hypercholesterolemia:

  • Patients with LDL-C above 190 mg/dL do not need a 10-year risk score calculated. These individuals should receive maximally tolerated statin therapy.
  • If patient is unable to achieve 50% reduction in LDL-C and/or have an LDL-C level of 100 mg/dL, the addition of ezetimibe therapy is reasonable.
  • If LDL-C is still greater than 100mg/dL on a statin plus ezetimibe, the addition of a PCSK9 inhibitor may be considered. It should be recognized that the addition of a PCSK9 in this circumstance is classified as a weak recommendation.
 

 

Diabetes mellitus in adults:

  • In patients aged 40-75 years with diabetes, regardless of 10-year ASCVD risk, should be prescribed a moderate-intensity statin (strong recommendation).
  • In adults with diabetes mellitus and multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with goal to reduce LDL-C by more than 50%.
  • In adults with diabetes mellitus and 10-year ASCVD risk of 20% or higher, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce LDL-C levels by 50% or more.
  • In patients aged 20-39 years with diabetes that is either of long duration (at least 10 years, type 2 diabetes mellitus; at least 20 years, type 1 diabetes mellitus), or with end-organ damage including albuminuria, chronic renal insufficiency, retinopathy, neuropathy, or ankle-brachial index below 0.9, it may be reasonable to initiate statin therapy (weak recommendation).

Primary prevention in adults: Adults with LDL 70-189 mg/dL and a 10-year risk of a first ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the pooled cohort equation. Adults should be categorized according to calculated risk of developing ASCVD: low risk (less than 5%), borderline risk (5% to less than 7.5%), intermediate risk (7.5% and higher to less than 20%), and high risk (20% and higher) (strong recommendation:

  • Individualized risk and treatment discussion should be done with clinician and patient.
  • Adults in the intermediate-risk group (7.5% and higher to less than 20%), should be placed on moderate-intensity statin with LDL-C goal reduction of more than 30%; for optimal risk reduction, especially in high-risk patients, an LDL-C reduction of more than 50% (strong recommendation).
  • Risk-enhancing factors can favor initiation of intensification of statin therapy.
  • If a decision about statin therapy is uncertain, consider measuring coronary artery calcium (CAC) levels. If CAC is zero, statin therapy may be withheld or delayed, except those with diabetes as above, smokers, and strong familial hypercholesterolemia with premature ASCVD. If CAC score is 1-99, it is reasonable to initiate statin therapy for patients older than age 55 years; If CAC score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate a statin.

Statin safety: Prior to initiation of a statin, a clinician-patient discussion is recommended detailing ASCVD risk reduction and the potential for side effects/drug interactions. In patients with statin-associated muscle symptoms (SAMS), a detailed account for secondary causes is recommended. In patients with true SAMS, it is recommended to check a creatine kinase level and hepatic function panel; however, routine measurements are not useful. In patients with statin-associated side effects that are not severe, reassess and rechallenge patient to achieve maximal lowering of LDL-C with a modified dosing regimen.
 

The bottom line

Lifestyle modification is important at all ages, with specific population-guided strategies for lowering cholesterol in subgroups as discussed above. Major changes to the AHA/ACC Cholesterol Clinical Practice Guidelines now mention new agents for lowering cholesterol and using CAC levels as predictability scoring.

Reference

Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Nov 10.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Palko is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

The purpose of this guideline is to provide direction for the management of patients with high blood cholesterol to decrease the incidence of atherosclerotic vascular disease. The update was undertaken because new evidence has emerged since the publication of the 2013 ACC/AHA cholesterol guideline about additional cholesterol-lowering agents including ezetimibe and PCSK9 inhibitors.

Dr. Gregory Palko and Dr. Neil Skolnik of Abington (Pa.) Jefferson Health
Dr. Gregory Palko and Dr. Neil Skolnik

Measurement and therapeutic modalities

In adults aged 20 years and older who are not on lipid-lowering therapy, measurement of a lipid profile is recommended and is an effective way to estimate atherosclerotic cardiovascular disease (ASCVD) risk and documenting baseline LDL-C.

Statin therapy is divided into three categories: High-intensity statin therapy aims for lowering LDL-C levels by more than 50%, moderate-intensity therapy by 30%-49%, and low-intensity therapy by less than 30%.
 

Cholesterol management groups

In all individuals at all ages, emphasizing a heart-healthy lifestyle, meaning appropriate diet and exercise, to decrease the risk of developing ASCVD should be advised.

Individuals fall into groups with distinct risk of ASCVD or recurrence of ASCVD and the recommendations are organized according to these risk groups.

Secondary ASCVD prevention: Patients who already have ASCVD by virtue of having had an event or established diagnosis (MI, angina, cerebrovascular accident, or peripheral vascular disease) fall into the secondary prevention category:

  • Patients aged 75 years and younger with clinical ASCVD: High-intensity statin therapy should be initiated with aim to reduce LDL-C levels by 50%. In patients who experience statin-related side effects, a moderate-intensity statin should be initiated with the aim to reduce LDL-C by 30%-49%.
  • In very high-risk patients with an LDL-C above 70 mg/dL on maximally tolerated statin therapy, it is reasonable to consider the use of a non–statin cholesterol-lowering agent with an LDL-C goal under 70 mg/dL. Ezetimibe (Zetia) can be used initially and if LDL-C remains above 70 mg/dL, then consideration can be given to the addition of a PCSK9-inhibitor therapy (strength of recommendation: ezetimibe – moderate; PCSK9 – strong). The guideline discusses that, even though the evidence supports the efficacy of PCSK9s in reducing the incidence of ASCVD events, the expense of PCSK9 inhibitors give them a high cost, compared with value.
  • For patients more than age 75 years with established ASCVD, it is reasonable to continue high-intensity statin therapy if patient is tolerating treatment.

Severe hypercholesterolemia:

  • Patients with LDL-C above 190 mg/dL do not need a 10-year risk score calculated. These individuals should receive maximally tolerated statin therapy.
  • If patient is unable to achieve 50% reduction in LDL-C and/or have an LDL-C level of 100 mg/dL, the addition of ezetimibe therapy is reasonable.
  • If LDL-C is still greater than 100mg/dL on a statin plus ezetimibe, the addition of a PCSK9 inhibitor may be considered. It should be recognized that the addition of a PCSK9 in this circumstance is classified as a weak recommendation.
 

 

Diabetes mellitus in adults:

  • In patients aged 40-75 years with diabetes, regardless of 10-year ASCVD risk, should be prescribed a moderate-intensity statin (strong recommendation).
  • In adults with diabetes mellitus and multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with goal to reduce LDL-C by more than 50%.
  • In adults with diabetes mellitus and 10-year ASCVD risk of 20% or higher, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce LDL-C levels by 50% or more.
  • In patients aged 20-39 years with diabetes that is either of long duration (at least 10 years, type 2 diabetes mellitus; at least 20 years, type 1 diabetes mellitus), or with end-organ damage including albuminuria, chronic renal insufficiency, retinopathy, neuropathy, or ankle-brachial index below 0.9, it may be reasonable to initiate statin therapy (weak recommendation).

Primary prevention in adults: Adults with LDL 70-189 mg/dL and a 10-year risk of a first ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the pooled cohort equation. Adults should be categorized according to calculated risk of developing ASCVD: low risk (less than 5%), borderline risk (5% to less than 7.5%), intermediate risk (7.5% and higher to less than 20%), and high risk (20% and higher) (strong recommendation:

  • Individualized risk and treatment discussion should be done with clinician and patient.
  • Adults in the intermediate-risk group (7.5% and higher to less than 20%), should be placed on moderate-intensity statin with LDL-C goal reduction of more than 30%; for optimal risk reduction, especially in high-risk patients, an LDL-C reduction of more than 50% (strong recommendation).
  • Risk-enhancing factors can favor initiation of intensification of statin therapy.
  • If a decision about statin therapy is uncertain, consider measuring coronary artery calcium (CAC) levels. If CAC is zero, statin therapy may be withheld or delayed, except those with diabetes as above, smokers, and strong familial hypercholesterolemia with premature ASCVD. If CAC score is 1-99, it is reasonable to initiate statin therapy for patients older than age 55 years; If CAC score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate a statin.

Statin safety: Prior to initiation of a statin, a clinician-patient discussion is recommended detailing ASCVD risk reduction and the potential for side effects/drug interactions. In patients with statin-associated muscle symptoms (SAMS), a detailed account for secondary causes is recommended. In patients with true SAMS, it is recommended to check a creatine kinase level and hepatic function panel; however, routine measurements are not useful. In patients with statin-associated side effects that are not severe, reassess and rechallenge patient to achieve maximal lowering of LDL-C with a modified dosing regimen.
 

The bottom line

Lifestyle modification is important at all ages, with specific population-guided strategies for lowering cholesterol in subgroups as discussed above. Major changes to the AHA/ACC Cholesterol Clinical Practice Guidelines now mention new agents for lowering cholesterol and using CAC levels as predictability scoring.

Reference

Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Nov 10.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Palko is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

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