What are the guidelines for the use of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins?

From the Guidelines

Statin therapy should be initiated or continued as first-line therapy in women and men ≤75 years of age who have clinical atherosclerotic cardiovascular disease (ASCVD), unless contraindicated, with high-intensity statin therapy as the preferred option 1, 2.

Key Points to Consider

• High-intensity statin therapy has been shown to confer incremental clinical benefit compared with less intensive therapy, with a 15% further reduction in major vascular events 1.
• The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommends treatment of patients ≤75 years of age who have clinical ASCVD with high-intensity statin therapy 2.
• Moderate-intensity statin therapy is recommended for individuals with clinical ASCVD >75 years of age, or in those who have contraindications or intolerance to high-intensity regimens 2.
• Statin therapy should be individualized in persons >75 years of age according to the potential for ASCVD risk-reduction benefits, adverse effects, drug-drug interactions, and patient preferences 1, 2.

Statin Therapy Recommendations

• High-intensity statins (atorvastatin 40-80mg or rosuvastatin 20-40mg) are recommended for those with established cardiovascular disease or at highest risk 1, 2.
• Moderate-intensity statins are appropriate for primary prevention or in individuals who cannot tolerate high-intensity statins 2.
• Patients should have baseline liver function tests and be monitored for muscle symptoms, which occur in 5-10% of users 1.

Additional Considerations

• Statins work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver and increasing LDL receptor expression, which enhances cholesterol clearance from the bloodstream 1.
• They also have pleiotropic effects including improved endothelial function and reduced inflammation 1.
• Statins should be taken consistently, typically in the evening for most types, and patients should maintain a heart-healthy diet and regular exercise while on therapy 1, 2.

From the FDA Drug Label

Rosuvastatin tablets are an HMG Co-A reductase inhibitor (statin) indicated: (1) 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. As an adjunct to diet to: reduce LDL-C in adults with primary hyperlipidemia.

Pravastatin sodium is an HMG-CoA reductase inhibitor (statin) indicated (1): To reduce the risk of myocardial infarction, myocardial revascularization procedures, and cardiovascular mortality in adults with elevated low-density lipoprotein cholesterol (LDL-C) without clinically evident coronary heart disease (CHD) To reduce the risk of coronary death, myocardial infarction, myocardial revascularization procedures, stroke or transient ischemic attack, and slow the progression of coronary atherosclerosis in adults with clinically evident CHD. As an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia

Guidelines for statin use include:

• Reducing the risk of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk of CV disease
• Reducing LDL-C in adults with primary hyperlipidemia
• Reducing the risk of myocardial infarction, myocardial revascularization procedures, and cardiovascular mortality in adults with elevated LDL-C
• Reducing the risk of coronary death, myocardial infarction, myocardial revascularization procedures, stroke or transient ischemic attack, and slowing the progression of coronary atherosclerosis in adults with clinically evident CHD Key considerations for statin use include:
• Age
• High-sensitivity C-reactive protein (hsCRP) levels
• Additional CV risk factors
• LDL-C levels
• Presence of coronary heart disease 3, 4

From the Research

Guidelines for Statin Use

• The use of high-intensity statins is recommended for patients with atherosclerotic cardiovascular disease (ASCVD) and high-risk patients without clinical ASCVD 5.
• High-risk primary prevention patients include those with severe hypercholesterolemia, diabetes with associated risk factors, and patients aged 40 to 75 years with a 10-year risk for ASCVD of 20% or greater 5.
• For patients with a 10-year risk of 7.5% to less than 20%, coronary artery calcium scoring is an option to determine the need for statin therapy 5.
• The US Preventive Services Task Force recommends that clinicians prescribe a statin for the primary prevention of cardiovascular disease for adults aged 40 to 75 years who have one or more cardiovascular disease risk factors and an estimated 10-year cardiovascular disease risk of 10% or greater 6.

Combination Therapy

• The combination of ezetimibe and rosuvastatin is a potential option for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease 7, 8.
• The current evidence indicates that combination therapy outperforms statin monotherapy in reduction of low-density lipoprotein cholesterol and patients are more likely to achieve their target low-density lipoprotein cholesterol goal level 8.
• The use of nonstatin therapies (ezetimibe and PCSK9 inhibitors) in addition to maximally tolerated statin therapy is recommended for individuals whose low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels remain above certain thresholds after statin treatment 9.

Safety and Efficacy

• The benefits of statin therapy far outweigh any real or perceived risks, and the overwhelming evidence suggests that statin therapy is safe and effective in both primary and secondary prevention of cardiovascular disease 9.
• The potential harmful effects of statin therapy on muscle and liver have been known for some time, but new concerns have emerged regarding the risk of new-onset diabetes mellitus, cognitive impairment, and hemorrhagic stroke associated with the use of statins 9.