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

From the Guidelines

Statins should be initiated in patients with established atherosclerotic cardiovascular disease (ASCVD), LDL cholesterol ≥190 mg/dL, diabetes aged 40-75 years, or those with a 10-year ASCVD risk ≥7.5%. Start with moderate-intensity statins like atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily for most patients. High-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) are recommended for patients with established ASCVD, very high LDL levels, or diabetes with multiple risk factors. Begin with lower doses in elderly patients, those with renal impairment, or patients taking medications with potential drug interactions. Monitor liver function tests at baseline and lipid panels after 4-12 weeks to assess response. Patients should be counseled about possible muscle pain and advised to report significant symptoms. Statins work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver, increasing LDL receptor expression, and enhancing clearance of LDL from circulation. This leads to decreased cardiovascular events through both lipid-lowering and pleiotropic effects including improved endothelial function and reduced inflammation, as supported by the 2018 American Heart Association/American College of Cardiology/Multisociety Cholesterol Guideline 1.

Some key points to consider when starting statin therapy include:

• Estimating 10-year ASCVD risk using a risk calculator
• Evaluating risk-enhancing factors, such as family history of premature ASCVD or high-risk ethnicity
• Considering patient preferences and values in shared decision making
• Monitoring for potential adverse effects, such as muscle pain or liver enzyme elevations
• Adjusting the statin dose or type based on patient response and tolerability, as recommended by the American College of Cardiology/American Heart Association Task Force on Performance Measures 1.

Overall, the goal of statin therapy is to reduce the risk of cardiovascular events and improve patient outcomes, while minimizing potential adverse effects and considering individual patient factors.

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. As an adjunct to diet to: reduce LDL-C in adults with primary hyperlipidemia.

The starting statin guidelines for rosuvastatin are as follows:

• Adults: The recommended dosage range is 5 mg to 40 mg once daily 2.
• Pediatric Patients with HeFH: The recommended dosage range is 5 mg to 10 mg once daily for patients aged 8 to less than 10 years of age, and 5 mg to 20 mg once daily for patients aged 10 years and older 2.
• Asian Patients: Initiate at 5 mg once daily, and consider risks and benefits of treatment if not adequately controlled at doses up to 20 mg once daily 2.
• Patients with Severe Renal Impairment: Initiate at 5 mg once daily; do not exceed 10 mg once daily 2.

From the Research

Starting Statin Guidelines

• The decision to start statin therapy is based on the patient's risk of atherosclerotic cardiovascular disease (ASCVD) events, with statins recommended as a first-line therapy for primary and secondary prevention of ASCVD 3, 4.
• Patients at high risk for ASCVD, including those with a history of cardiovascular disease, diabetes, hypertension, or smoking, and an estimated 10-year CVD event risk of 10% or greater, should be prescribed a statin for primary prevention 5.
• For patients with an estimated 10-year CVD event risk of 7.5% to less than 10%, statin use is recommended, but the likelihood of benefit is smaller than in those with a 10-year risk of 10% or greater 5.
• High-intensity statins are recommended for patients at high risk for ASCVD, with a goal of reducing low-density lipoprotein (LDL) cholesterol by 50% or greater 6.
• The potency and dose of statin therapy should be tailored to the individual's cardiovascular risk and tolerance to potential adverse effects 3.

Patient Selection

• Patients with ASCVD are candidates for high-intensity statins, with the addition of non-statin drugs (ezetimibe, PCSK9 inhibitors, etc.) for those at very high risk 6.
• 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 6.
• Coronary artery calcium scoring can be used to up-classify patients with a 10-year risk of 7.5% to less than 20% to high risk if the coronary artery calcium score is 300 or more Agatston units 6.

Safety and Adverse Events

• 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% 7.
• The risk of statin-induced newly diagnosed diabetes mellitus is approximately 0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied 7.
• Statin use is not associated with an increased risk of cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis 7.