What are the guidelines for statin (HMG-CoA reductase inhibitor) use?

From the Guidelines

Statin use is recommended for patients with established cardiovascular disease, diabetes, or high LDL cholesterol levels, with high-intensity statins being the preferred choice for those with atherosclerotic cardiovascular disease or diabetes with multiple risk factors. The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol recommends initiating high-intensity statin therapy in patients with clinical atherosclerotic cardiovascular disease (ASCVD) who are ≤75 years of age, unless contraindicated 1. For patients with ASCVD who are >75 years of age, it is reasonable to evaluate the potential for ASCVD risk-reduction benefits and for adverse effects, drug-drug interactions, and to consider patient preferences when initiating a moderate- or high-intensity statin 1.

Key Considerations

• High-intensity statin therapy should be initiated or continued as first-line therapy in women and men ≤75 years of age who have clinical ASCVD, unless contraindicated 1.
• In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL, at a 10-year ASCVD risk of ≥7.5%, start a moderate-intensity statin if a discussion of treatment options favors statin therapy 1.
• Risk-enhancing factors, such as family history of premature ASCVD, persistently elevated LDL-C levels ≥160 mg/dL, and metabolic syndrome, favor initiation of statin therapy in patients at intermediate risk (10-year risk of 7.5% to 19.9%) 1.
• Before starting treatment, baseline liver function tests and lipid panels should be obtained, with follow-up testing 4-12 weeks after initiation to assess response and adherence 1.

Statin Options

• First-line statins include atorvastatin (10-80 mg daily) and rosuvastatin (5-40 mg daily) for high-intensity therapy, while moderate-intensity options include simvastatin (20-40 mg daily) and pravastatin (40-80 mg daily) 1.
• Treatment intensity should be matched to cardiovascular risk, with high-intensity statins for those with atherosclerotic cardiovascular disease or diabetes with multiple risk factors, and moderate-intensity for most other at-risk patients 1.

Side Effects and Monitoring

• Side effects may include muscle pain, mild liver enzyme elevations, and slightly increased diabetes risk, but benefits typically outweigh these risks for indicated patients 1.
• 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.

From the FDA Drug Label

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. 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 guidelines for statin use are as follows:

• Primary Prevention: Statins are indicated to reduce the risk of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk of CV disease.
• Secondary Prevention: Statins are indicated 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.
• LDL-C Reduction: Statins are indicated as an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia, and to reduce LDL-C in adults and pediatric patients with heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH) 2, 3, 4.

From the Research

Guidelines for Statin Use

The use of statins is a crucial aspect of managing high cardiovascular risk patients. According to 5, statins are the drug of choice for patients at increased risk of atherosclerotic cardiovascular disease (ASCVD) and are effective in reducing LDL cholesterol and the risk of mortality and coronary artery disease in high-risk groups.

Patient Selection

The decision to initiate statin therapy should be based on individual consideration and shared decision-making, taking into account the patient's complexity and comorbidities 5. High-intensity statins are recommended for patients with ASCVD (secondary prevention) and high-risk patients without clinical ASCVD 6.

Treatment Intensity

The latest guidelines emphasize that treatment intensity should increase with increasing cardiovascular risk 5. High-intensity statins can reduce LDL cholesterol by 50% or greater, and are recommended for patients with ASCVD and high-risk primary prevention patients 6.

Alternative Therapies

For patients who cannot tolerate high-intensity statins, a reasonable approach is to combine a moderate-intensity statin with ezetimibe 6. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can also be used as an adjunct to statin therapy to reduce LDL cholesterol levels substantially and reduce risk in very high-risk patients 7.

Comparison of Statins

Studies have compared the effectiveness of different statins in achieving cholesterol goals and improving plasma lipids. For example, rosuvastatin has been shown to be more effective than atorvastatin, simvastatin, and pravastatin in achieving LDL cholesterol goals and improving lipid levels in hypercholesterolemic patients with or without the metabolic syndrome 8, 9.

Key Points

• Statins are the drug of choice for patients at increased risk of ASCVD
• High-intensity statins are recommended for patients with ASCVD and high-risk primary prevention patients
• Treatment intensity should increase with increasing cardiovascular risk
• Alternative therapies, such as ezetimibe and PCSK9 inhibitors, can be used for patients who cannot tolerate high-intensity statins
• Different statins have varying levels of effectiveness in achieving cholesterol goals and improving plasma lipids 5, 6, 7, 8, 9