- ACRONYMS AND DEFINITIONS
- AHA - American Heart Association
- CV - Cardiovascular
- LDL - Low Density Lipoprotein. See LDL cholesterol for more.
- Primary prevention - prevention of a disease in a patient before the underlying disease has been established in the patient
- Secondary prevention - prevention of the recurrence of an event (ex. heart attack) or illness (ex. cancer) after the underlying disease has already been established in the patient
- USPSTF - U.S. Preventive Services Task Force
- PRIMARY PREVENTION RECOMMENDATIONS
- OVERVIEW
- Primary prevention involves treating high cholesterol in patients who have not been diagnosed with clinical atherosclerotic cardiovascular disease
- Clinical atherosclerotic cardiovascular disease is defined as history of heart attack, angina, arterial revascularization (coronary or other), stroke, TIA, or peripheral artery disease.
- AHA 2013 PRIMARY PREVENTION RECOMMENDATIONS
- The AHA/ACC 2013 guidelines are listed below. In the past, specific LDL goals were targeted. The 2013 guidelines changed the focus of therapy to statin treatment goals.
- In 2016, the American College of Cardiology published guidelines for the use of non-statin medications in LDL lowering. Those recommendations have been incorporated into the AHA recommendations.
- All recommendations are for adults ≥ 21 years old
Any patient with LDL cholesterol > 190 mg/dl
- If cannot tolerate high-intensity statin, then moderate-intensity statin should be used
- For patients ≥ 75 years old, risk/benefit ratio should be considered [1]
- Response: For patients who do not achieve ≥ 50% LDL reduction (or may consider LDL < 100 mg/dl) on maximum statin, consider adding one of the following:
- Ezetimibe (preferred)
- PCSK9 inhibitors (preferred)
- Bile acid sequestrant - if triglycerides < 300 mg/dl (second-line) [3]
Diabetics with LDL cholesterol 70 - 189 mg/dl
- For patients 40 - 75 years with a 10-year cardiovascular risk ≥ 7.5%, high-intensity statin is reasonable (risk calculator)
- For patients < 40 or > 75 years old, risk/benefit ratio should be considered [1]
- Response: For patients (40 - 75 years old) who do not achieve ≥ 50% LDL reduction (or may consider LDL < 100 mg/dl or non-HDL < 130 mg/dl) on maximum statin, consider adding one of the following:
- Ezetimibe (first-line)
- Bile acid sequestrant - if triglycerides < 300 mg/dl (second-line) [3]
- Non-HDL = Total cholesterol - HDL
Non-diabetics with LDL cholesterol 70 - 189 mg/dl (adults 40 - 75 years old)
- Estimate the 10-risk of cardiovascular disease with the risk calculator
- If risk is ≥ 7.5%, then treat with moderate- to high-intensity statin (statin chart)
- If risk is 5% - 7.5%, then moderate-intensity statin is reasonable [1]
- Reponse: For patients (40 - 75 years old) with a 10-year risk ≥ 7.5% and high-risk markers* who do not achieve ≥ 50% LDL reduction (or may consider LDL < 100 mg/dl) on maximum statin, consider adding one of the following:
- Ezetimibe (preferred)
- Bile acid sequestrant - if triglycerides < 300 mg/dl (second-line) [3]
- *High-risk markers defined as any of the following: 10-year CVD risk ≥ 20%, LDL ≥ 160 mg/dl, poorly-controlled major CVD risk factor, family history of premature CVD, evidence of accelerated subclinical atherosclerosis (e.g. coronary artery calcium), elevated CRP, or other risk-modifying condition (e.g. HIV, chronic kidney disease, inflammatory disorders)
- USPSTF 2016 RECOMMENDATIONS
- In 2015, the USPSTF issued draft recommendations for statin use in the primary prevention of cardiovascular disease in adults
Use a low- to moderate-intensity statin in patients who meet all of the following criteria:
- Age 40 - 75 years
- One or more cardiovascular disease risk factors is present (e.g. high cholesterol (defined as LDL ≥ 130 mg/dl), diabetes, hypertension, smoking)
- Estimated 10-year risk of a cardiovascular event is ≥ 10% (risk calculator) [Grade B]
A low- to moderate-intensity statin may be beneficial in some patients who meet all of the following criteria:
- Age 40 - 75 years
- One or more cardiovascular disease risk factors is present (e.g. high cholesterol (defined as LDL ≥ 130 mg/dl), diabetes, hypertension, smoking)
- Estimated 10-year risk of a cardiovascular event is 7.5% - 10% (risk calculator) [Grade C]
For patients ≥ 76 years old:
- There is insufficient evidence to make a recommendation [Grade I] [2]
- SECONDARY PREVENTION RECOMMENDATIONS
- OVERVIEW
- Secondary prevention involves treating high cholesterol in patients who have already been diagnosed with atherosclerotic cardiovascular disease
- The AHA/ACC 2013 guidelines are listed below
- In 2016, the American College of Cardiology published guidelines for the use of non-statin medications in LDL lowering. These recommendations are also listed.
- In the past, specific LDL goals were targeted. The 2013 guidelines changed the focus of therapy to statin treatment goals.
Patients with clinical atherosclerotic cardiovascular disease (ASCVD✝)
- If cannot tolerate high-intensity statin, then moderate-intensity statin should be used
- For patients ≥ 75 years old, risk/benefit ratio should be considered [1]
- Patients with stable clinical ASCVD✝ without comorbidities* who do not achieve ≥ 50% LDL reduction (or may consider LDL < 100 mg/dl) on maximum statin
- Ezetimibe (first-line)
- Bile acid sequestrant - if triglycerides < 300 mg/dl (second-line)
- PCSK9 inhibitors - may be added to or may replace other therapies (third-line) [3]
- Patients with clinical ASCVD✝ with comorbidities* who do not achieve ≥ 50% LDL reduction (or may consider LDL < 70 mg/dl or non-HDL < 100 mg/dl) on maximum statin
- Ezetimibe (first-line)
- Bile acid sequestrant - if triglycerides < 300 mg/dl (second-line)
- PCSK9 inhibitors - may be added to or may replace other therapies (third-line) [3]
- Patients with clinical ASCVD✝ with LDL > 190 mg/dl who do not achieve ≥ 50% LDL reduction (or may consider LDL < 70 mg/dl) on maximum statin
- Ezetimibe (preferred)
- PCSK9 inhibitors - (preferred)
- Bile acid sequestrant - if triglycerides < 300 mg/dl (second-line) [3]
- ✝ASCVD - clinical atherosclerotic cardiovascular disease defined as history of heart attack, stable or unstable angina, arterial revascularization (coronary or other), stroke, TIA, or peripheral artery disease
- *Comorbidities defined as diabetes, recent (< 3 months) acute CVD event, CVD event while already taking statin, baseline LDL ≥ 190 mg/dl, poorly-controlled major CVD risk factor, elevated lipoprotein(a), chronic kidney disease
- Non-HDL = Total cholesterol - HDL
- STATIN INTENSITY CHART
| High-intensity statin therapy (lowers cholesterol by ≥50%) |
Moderate-intensity statin therapy (lowers cholesterol by 30 - 50%) |
Low-intensity statin therapy (lowers cholesterol by < 30%) |
|---|---|---|
|
|
|
- RISK FACTORS FOR ADVERSE EFFECTS FROM STATINS
- For patients with the following risk factors, a lower intensity statin may be considered:
- Multiple or serious comorbidities, including impaired kidney or liver function
- History of previous statin intolerance or muscle disorders
- Unexplained ALT elevations > 3 times upper limits of normal
- Patient characteristics or concomitant use of drugs affecting statin metabolism
- Age > 75 years of age
- History of hemorrhagic stroke (see statins in hemorrhagic stroke)
- Asian ancestry
- MONITORING STATIN THERAPY
- Cholesterol
- Recheck cholesterol 4 - 12 weeks after starting therapy
- If response is appropriate (≥ 50% reduction with high-intensity therapy or 30 - 50% with moderate-intensity therapy), recheck in 3 - 12 months
- Liver function tests
- Baseline ALT (Alanine Aminotransferase) should be measured before starting therapy
- During statin therapy, it is reasonable to measure hepatic function if symptoms suggesting hepatotoxicity arise (e.g., unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine or yellowing of the skin or sclera)
- Muscle toxicity
- CK should not be routinely measured
- Baseline measurement of CK is reasonable for individuals believed to be at increased risk for adverse muscle events based on a personal or family history of statin intolerance or muscle disease, clinical presentation, or concomitant drug therapy that might increase the risk for myopathy
- During statin therapy, it is reasonable to measure CK in individuals with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue.
- Managing myalgias (muscle pain)
- Discontinue statin. If symptoms resolve, retry statin to develop a causal relationship.
- If causal relationship exists, discontinue original statin. Once muscle symptoms resolve, use a low dose of a different statin.
- CARDIOVASCULAR RISK CALCULATORS
- AHA Cardiovascular Risk Calculator
- Framingham risk calculator (NOTE:The Framingham calculator cannot be used for diabetics)
- The AHA and the Framingham risk calculators have both been shown to overestimate cardiovascular risk in trials. A recent study in the Annals of Internal Medicine found that 4 different risk calculators (AHA and 3 Framingham-based calculators) overestimated cardiovascular events by 37 - 154% in men, and 8 - 67% in women. [PMID 25686167]
Criticisms
- REFERENCES
- 1 - PMID 24222016
- 2 - USPSTF website
- 3 - PMID 27046161 - ACC Non-statin recommendations for LDL