From the Guidelines
Statin therapy should be initiated for patients with clinical atherosclerotic cardiovascular disease (ASCVD) with high-intensity statin therapy as the primary recommendation, but if this cannot be used, moderate-intensity statin therapy can be initiated. The goal of statin therapy is to achieve a ≥50% reduction in LDL-C levels, and if LDL-C levels remain ≥70 mg/dL (≥1.8 mmol/L) on maximally tolerated statin therapy, adding ezetimibe may be reasonable 1.
Key Considerations
- High-intensity statin therapy is indicated for clinical ASCVD, with options including atorvastatin 40-80mg daily or rosuvastatin 20-40mg daily.
- Moderate-intensity statin therapy can be initiated if high-intensity statin therapy cannot be used, with options including atorvastatin 10-20mg, rosuvastatin 5-10mg, simvastatin 20-40mg, or pravastatin 40-80mg daily.
- In patients >75 years of age with ASCVD, potential benefits versus adverse effects of statin therapy should be considered before initiation of statin therapy 1.
- In very high-risk patients with multiple high-risk clinical factors, ezetimibe can be added to maximally tolerated statin therapy, and if LDL-C levels remain ≥70 mg/dL (≥1.8 mmol/L), adding a PCSK9 inhibitor is reasonable if the cost/benefit ratio is favorable 1.
Monitoring and Follow-up
- Baseline lipid panels and liver function tests should be obtained before starting statin therapy.
- Patients should be counseled about potential side effects including muscle pain and rare liver issues, with follow-up testing recommended 4-12 weeks after initiation to assess LDL reduction and monitor for adverse effects.
Mechanism of Action
- Statins work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver, which leads to increased LDL receptor expression and enhanced clearance of LDL from the bloodstream, helping to stabilize existing plaques and prevent new plaque formation, significantly reducing cardiovascular events and mortality in both primary and secondary prevention settings 1.
From the FDA Drug Label
To reduce the risk of: Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD. Non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident CHD.
Statin Initiation for ASCVD: The FDA drug label for atorvastatin indicates that it is used to reduce the risk of myocardial infarction, stroke, and other cardiovascular events in adults with multiple risk factors for coronary heart disease, including those with and without clinically evident CHD, as well as in adults with type 2 diabetes mellitus and multiple risk factors for CHD.
- The recommended starting dosage is 10 or 20 mg once daily, with a dosage range of 10 mg to 80 mg once daily.
- Patients requiring LDL-C reduction >45% may start at 40 mg once daily 2.
From the Research
Statin Initiation and ASCVD
- Statins are recommended as a first-line therapy for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) 3, 4.
- The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol management guideline defines four statin benefit groups (SBGs) based on risk factors and laboratory lipid levels, including patients with ASCVD, high low-density lipoprotein cholesterol levels, diabetes mellitus, and estimated 10-year ASCVD risk 5.
- Post-guideline, there was a gradual increase in high-intensity statin initiation in patients with ASCVD and in those with high low-density lipoprotein cholesterol levels 5.
Benefits of Statin Therapy
- Statins have been proven to effectively reduce the risk of ASCVD and are recommended for primary and secondary prevention 3, 4.
- Statin therapy can reduce low-density lipoprotein cholesterol (LDL-C) levels and decrease the risk of major cardiovascular events 3, 6.
- However, statins may not be sufficient in decreasing LDL-C levels, and pose a significant on-treatment residual risk of major cardiovascular events 3.
Combination Therapy
- Ezetimibe, a cholesterol absorption inhibitor, can be added to statin therapy to achieve additional LDL-C reduction and reduce ASCVD risk 3, 7.
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab, can be used in combination with statins to lower LDL-C levels and reduce ASCVD risk 3, 6.
- The use of PCSK9 inhibitors is recommended for very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 6.