What are the indications for primary prevention with statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

Statins are indicated for primary prevention of cardiovascular disease in individuals with elevated risk factors but without established cardiovascular disease, specifically those with LDL cholesterol ≥190 mg/dL, diabetes mellitus (age 40-75 with LDL 70-189 mg/dL), and those with calculated 10-year ASCVD risk ≥7.5%. The main indications for statin therapy include patients with high LDL cholesterol levels, diabetes, and those with an elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD) [ 1 ]. Common statins used for primary prevention include atorvastatin, rosuvastatin, simvastatin, and pravastatin.

Key Considerations for Statin Therapy

• Treatment should be initiated at moderate intensity for most patients, with high-intensity therapy reserved for those at highest risk [ 1 ].
• Baseline liver function tests and lipid panel should be checked before starting therapy, with follow-up lipid panel in 4-12 weeks to assess response.
• Statins work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver and increasing LDL receptor expression, which enhances LDL clearance from the bloodstream [ 1 ].
• This mechanism effectively lowers LDL cholesterol by 20-60% depending on the statin and dose, significantly reducing the risk of cardiovascular events even in those without established disease.

Decision Making for Primary Prevention

• The decision to initiate statin therapy for primary prevention should be based on a comprehensive assessment of the patient's risk factors, including LDL cholesterol level, presence of diabetes, and calculated 10-year ASCVD risk [ 1 ].
• For patients with borderline or intermediate risk, clinical judgment is required to initiate statin treatment, taking into account risk-enhancing factors and patient preferences [ 1 ].
• The use of risk assessment tools, such as the Pooled Cohort Equations, can help guide decision making for primary prevention [ 1 ].

Recent Guidelines and Recommendations

• The 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline recommends statin therapy for primary prevention in adults aged 40-75 years with LDL-C levels of at least 1.8 mmol/L (70 mg/dL) and a 10-year ASCVD risk of 7.5% or higher [ 1 ].
• The US Preventive Services Task Force recommends that clinicians offer low- to moderate-dose statin therapy to adults aged 40-75 years with one or more cardiovascular risk factors and a calculated 10-year cardiovascular event risk of 7.5% to 10% [ 1 ].

From the FDA Drug Label

To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor. The primary prevention statin indication is to reduce the risk of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor 2.

• The indication is for adults with an increased risk of CV disease.
• The risk is based on age, hsCRP, and at least one additional CV risk factor.

From the Research

Primary Prevention Statin Indication

• The use of statins for primary prevention of cardiovascular disease (CVD) is recommended for adults aged 40 to 75 years with one or more CVD risk factors and an estimated 10-year CVD risk of 10% or greater 3.
• Statins have been shown to significantly reduce cardiovascular morbidity and mortality in patients with and without coronary heart disease, with a 9% reduction in all-cause mortality and a 25% reduction in major vascular events per 1.0 mmol/l reduction in low-density lipoprotein cholesterol 4.
• The benefits of statins for primary prevention generally outweigh the reported harms, including an 18% increase in incident diabetes 4.
• For adults aged 40 to 75 years with one or more CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10%, the US Preventive Services Task Force recommends that clinicians selectively offer a statin for primary prevention 3.
• In patients who are statin intolerant, alternative treatment options such as ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) may be considered, with PCSK9i showing significantly greater reduction in LDL-C levels compared to ezetimibe 5, 6.

Statin Intolerance and Alternative Treatments

• Statin intolerance is a challenge, with 5% to 10% of statin-treated patients reporting intolerance, mostly due to muscle-related adverse effects 6.
• Ezetimibe and PCSK9i are alternative treatment options for statin-intolerant patients, with PCSK9i showing marked LDL-C reduction 5, 6.
• The Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 3 (GAUSS-3) trial compared the effectiveness of evolocumab vs ezetimibe in statin-intolerant patients, with evolocumab showing significant LDL-C reduction 6.

Guidelines and Recommendations

• The US Preventive Services Task Force recommends that clinicians prescribe a statin for primary prevention of CVD for adults aged 40 to 75 years with one or more CVD risk factors and an estimated 10-year CVD risk of 10% or greater 3.
• The American College of Cardiology and American Heart Association guidelines recommend statin therapy for primary prevention of CVD in adults with LDL-C levels of 190 mg/dL or higher, or those with diabetes, or those with an estimated 10-year CVD risk of 7.5% or higher 7.