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

From the Guidelines

Statins are primarily indicated for the prevention and management of cardiovascular disease by lowering cholesterol levels, and should be prescribed to patients with established atherosclerotic cardiovascular disease (ASCVD), including those with prior heart attacks, strokes, or peripheral artery disease, as well as for primary prevention in individuals with elevated LDL cholesterol levels or a calculated 10-year ASCVD risk score of 7.5% or higher, as recommended by the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults 1.

Indications for Statin Therapy

The indications for statin therapy include:

• Patients with established ASCVD, including those with prior heart attacks, strokes, or peripheral artery disease
• Primary prevention in individuals with elevated LDL cholesterol levels (typically above 190 mg/dL)
• Primary prevention in individuals with diabetes mellitus (particularly in those aged 40-75)
• Primary prevention in individuals with a calculated 10-year ASCVD risk score of 7.5% or higher

Choice of Statin and Dosage

The choice of statin and dosage depends on the desired LDL reduction, with:

• High-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) typically reducing LDL by ≥50%
• Moderate-intensity statins reducing LDL by 30-50%
• Low-intensity statins reducing LDL by <30%

Mechanism of Action

Statins work by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, thereby reducing LDL cholesterol production and increasing LDL receptor expression on hepatocytes, which enhances LDL clearance from the bloodstream.

Monitoring and Safety

Regular monitoring of liver function tests and assessment for muscle symptoms is recommended during statin therapy, especially when initiating treatment or adjusting dosages, as recommended by the 2017 AHA/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction 1.

Clinical Recommendations

The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommends:

• High-intensity statin therapy as first-line therapy in women and men ≤75 years of age who have clinical ASCVD, unless contraindicated
• Moderate-intensity statin therapy as the second option if high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present
• Evaluation of the potential for ASCVD risk-reduction benefits and for adverse effects, drug-drug interactions, and patient preferences when initiating a moderate- or high-intensity statin in individuals with clinical ASCVD >75 years of age 1.

From the FDA Drug Label

Rosuvastatin tablets are an HMG Co-A reductase inhibitor (statin) indicated: 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. reduce LDL-C and slow the progression of atherosclerosis in adults reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH) As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH) As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia.

The indications for HMG-CoA reductase inhibitors, commonly referred to as statins, are:

• To reduce the risk of major adverse cardiovascular events in adults without established coronary heart disease who are at increased risk of CV disease
• To reduce LDL-C in adults with primary hyperlipidemia
• To reduce LDL-C and slow the progression of atherosclerosis in adults
• To reduce LDL-C in adults and pediatric patients with heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH)
• To treat adults with primary dysbetalipoproteinemia and hypertriglyceridemia 2, 3, 2.

From the Research

Indications for HMG-CoA Reductase Inhibitors (Statins)

The indications for HMG-CoA reductase inhibitors, commonly referred to as statins, include:

• Reduction of the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease 4
• Primary prevention of cardiovascular disease in patients with elevated cardiovascular risk 5, 6
• Treatment of patients with established coronary artery disease (CAD) to reduce cardiovascular death, myocardial infarction, and coronary revascularization procedures 6, 7
• Prevention and treatment of heart failure, mainly by preventing myocardial infarction and reducing myocardial ischemia 8
• Reduction of low-density lipoprotein cholesterol levels, with the most effective statins producing a mean reduction of 55% to 60% at maximum dosage 4

Patient Populations

Statins are recommended for various patient populations, including:

• Patients with elevated cardiovascular risk, such as those with diabetes mellitus, hypertension, and hyperlipidemia 5, 6
• Patients with established atherosclerotic cardiovascular disease, including those with coronary artery disease, peripheral artery disease, and cerebrovascular disease 4, 7
• Patients with heart failure, although the evidence for this indication is weaker and the benefit may be smaller 8

Dosage and Intensity

The dosage and intensity of statin therapy vary depending on the patient's risk profile and the specific statin used. High-intensity statin therapy is associated with improved survival and reduced major adverse cardiovascular events in patients with peripheral artery disease 7. However, the optimal dosage and intensity of statin therapy for other patient populations are not as well established.