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

From the Guidelines

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. This recommendation is based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, as reported in the 2017 AHA/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction 1. The guideline emphasizes that 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.

Key Considerations for Statin Prescription

• Primary prevention candidates include patients with LDL-C ≥190 mg/dL, diabetes aged 40-75 years, or those with a 10-year ASCVD risk ≥7.5%
• Secondary prevention is indicated for all patients with established atherosclerotic cardiovascular disease
• Start with moderate-intensity statins (atorvastatin 10-20mg, rosuvastatin 5-10mg, simvastatin 20-40mg) for most patients, advancing to high-intensity statins (atorvastatin 40-80mg, rosuvastatin 20-40mg) for those with ASCVD, diabetes with multiple risk factors, or very high LDL-C
• Monitor liver function tests at baseline and as clinically indicated, and check lipid profiles 4-12 weeks after initiation to assess response

Mechanism of Action and Benefits

Statins work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver and upregulating LDL receptors, which increases LDL clearance from the bloodstream 1. This mechanism provides both lipid-lowering and pleiotropic anti-inflammatory effects that contribute to cardiovascular risk reduction. High-intensity statin therapy has been shown to reduce cardiovascular events, including coronary heart disease death, recurrent MI, cerebrovascular events, coronary revascularization, and all-cause mortality.

Side Effects and Management

Common side effects include myalgia (5-10% of patients), which can be managed by dose reduction, switching statins, or alternate-day dosing. Creatine kinase testing is unnecessary unless muscle symptoms develop.

From the Research

Guidelines for Prescribing Statins

• The decision to prescribe statins should be based on the patient's risk of atherosclerotic cardiovascular disease (ASCVD) 2.
• High-intensity statins are recommended for patients with ASCVD (secondary prevention) and high-risk patients without clinical ASCVD, with a goal of reducing low-density lipoprotein cholesterol (LDL-C) by 50% or greater 2.
• Patients at very high risk can benefit from the addition of non-statin drugs, such as ezetimibe, bile acid sequestrants, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, to high-intensity statins 2, 3.
• For patients who cannot tolerate high-intensity statins, a combination of a moderate-intensity statin and ezetimibe can be considered 2.

Patient Selection

• 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 2.
• Coronary artery calcium scoring can be used to assess risk in patients with a 10-year risk of 7.5% to less than 20% 2.
• Patients with a coronary artery calcium score of 300 or more Agatston units can be considered high risk 2.

Safety and Efficacy

• Statins have been shown to be safe and effective in reducing the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease 4.
• The risk of statin-induced serious muscle injury, including rhabdomyolysis, is less than 0.1%, and the risk of serious hepatotoxicity is approximately 0.001% 4.
• PCSK9 inhibitors have been shown to reduce LDL-C levels substantially and reduce the risk of cardiovascular events in patients with clinical ASCVD 3, 5.
• The addition of ezetimibe or PCSK9 inhibitors to statin therapy can reduce the risk of non-fatal myocardial infarction and stroke in adults at very high or high cardiovascular risk 5.