From the Guidelines
Statin therapy is recommended for primary prevention of cardiovascular disease in adults aged 40-75 with LDL cholesterol ≥70 mg/dL and a 10-year ASCVD risk ≥7.5%. The decision to start a statin should be based on a comprehensive risk assessment using tools like the ASCVD risk calculator, considering factors such as age, cholesterol levels, blood pressure, diabetes, and smoking status 1. Generally, statins are recommended for primary prevention in individuals with elevated risk factors, even without established heart disease. Common statins include atorvastatin (10-80 mg daily), rosuvastatin (5-40 mg daily), and simvastatin (20-40 mg daily). Moderate-intensity therapy (reducing LDL by 30-50%) is often sufficient for primary prevention, while high-intensity therapy may be considered for those at higher risk.
Key Considerations
- The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults recommends statin therapy for primary prevention in individuals with LDL-C ≥70 mg/dL and a 10-year ASCVD risk ≥7.5% 1.
- The USPSTF recommends initiating use of low- to moderate-dose statins in adults aged 40-75 with no history of CVD, ≥1 CVD risk factors, and a calculated 10-year CVD event risk of ≥10% 1.
- Statins work by inhibiting HMG-CoA reductase, reducing cholesterol synthesis in the liver and increasing LDL receptor expression, which lowers circulating LDL cholesterol.
- Regular monitoring of lipid levels and liver function tests is recommended, typically at 4-12 weeks after initiation and then annually.
- Potential side effects include muscle pain, mild liver enzyme elevations, and slightly increased risk of diabetes, though benefits typically outweigh these risks for those with appropriate indications.
Benefits and Risks
- The benefits of statin therapy for primary prevention of cardiovascular disease include a reduction in the risk of major cardiovascular events, such as heart attacks and strokes.
- The risks of statin therapy include muscle pain, mild liver enzyme elevations, and slightly increased risk of diabetes.
- The USPSTF concludes with moderate certainty that initiating use of low- to moderate-dose statins in adults aged 40-75 with no history of CVD, ≥1 CVD risk factors, and a calculated 10-year CVD event risk of ≥10% has at least a moderate net benefit 1.
From the FDA Drug Label
Rosuvastatin tablets are an HMG Co-A reductase inhibitor (statin) indicated: ( 1) 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. In the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of Atorvastatin on the occurrence of major CV disease events was assessed in 17,802 males (≥50 years) and females (≥60 years) who had no clinically evident CV disease, LDL-C levels <130 mg/dL and hsCRP levels ≥2 mg/L. Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0. 001) relative risk reduction of 44% and absolute risk reduction of 1. 2%
Statin use for primary prevention is indicated 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 JUPITER study 2 demonstrated a statistically significant reduction in major CV events with rosuvastatin treatment.
- Key benefits of rosuvastatin for primary prevention include:
- Reduction in risk of major adverse CV events
- Reduction in risk of nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization procedures
- Increase in HDL-C and reduction in LDL-C, hsCRP, total cholesterol, and serum triglyceride levels.
From the Research
Statin Use for Primary Prevention
- The US Preventive Services Task Force (USPSTF) recommends statin use for the primary prevention of cardiovascular disease (CVD) in adults aged 40 to 75 years with one or more CVD risk factors and an estimated 10-year CVD event risk of 10% or greater 3.
- The USPSTF also recommends that clinicians selectively offer a statin for primary prevention to adults aged 40 to 75 years with one or more CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10% 3.
- A study comparing the 2022 USPSTF recommendations with the 2018 AHA/ACC/MS Cholesterol guidelines found that approximately 15% fewer adults were eligible for statin therapy for primary prevention under the USPSTF recommendations 4.
Eligibility for Statin Therapy
- The 2022 USPSTF recommendations indicate eligibility for statin therapy in 31.8% of adults, representing 33.7 million adults, while the 2018 AHA/ACC/MS Cholesterol guidelines indicate eligibility in 46.8% of adults, representing 49.7 million adults 4.
- For adults with diabetes mellitus, the 2022 USPSTF recommendations suggest statin therapy in 63.0% of adults, compared to all adults with diabetes aged 40-75 years under the 2018 AHA/ACC/MS Cholesterol guidelines 4.
Effectiveness and Safety of Statins
- numerous large randomized clinical trials have shown that statin therapy is effective and safe for primary prevention of atherosclerotic CVD for adults aged 40 to 75 years 5.
- A systematic review, meta-analysis, and network meta-analysis of randomized trials found that statins as a class showed statistically significant risk reductions in non-fatal MI, CVD mortality, all-cause mortality, non-fatal stroke, unstable angina, and composite major cardiovascular events 6.
- However, statins also increased the risk of myopathy, renal dysfunction, and hepatic dysfunction, highlighting the need for a quantitative assessment of the benefit-harm balance 6.