What is the recommended statin therapy for patients at increased risk of cardiovascular events?

From the Guidelines

For patients at increased risk of cardiovascular events, high-intensity statin therapy is recommended, with atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily being the preferred options, as these regimens can lower LDL cholesterol by ≥50%. This recommendation is based on the most recent and highest quality study, which emphasizes the importance of high-intensity statin therapy in reducing cardiovascular events, including coronary heart disease death, recurrent MI, cerebrovascular events, coronary revascularization, and all-cause mortality 1.

Key Considerations

• High-intensity statin therapy has been shown to confer incremental clinical benefit compared with less intensive therapy, with a 15% further reduction in major vascular events 1.
• The 2024 standards of care in diabetes recommend using high-intensity statin therapy to reduce LDL cholesterol by ≥50% of baseline and to target an LDL cholesterol goal of <70 mg/dL (<1.8 mmol/L) for people with diabetes aged 40–75 years at higher cardiovascular risk 1.
• Moderate-intensity statins (atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, or pravastatin 40-80 mg daily) may be appropriate for those who cannot tolerate high-intensity therapy or have specific risk factors for statin-associated side effects.
• Treatment should be continued long-term as cardiovascular benefits accumulate over time, and patients should be monitored with lipid panels 4-12 weeks after initiation and then annually, along with liver function tests and assessment for muscle symptoms.

Monitoring and Follow-up

• Patients on statin therapy should be monitored regularly for potential side effects, such as muscle symptoms and liver enzyme elevations.
• Lipid panels should be checked 4-12 weeks after initiation of statin therapy and then annually to assess the effectiveness of treatment.
• The use of 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 1.

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. Adults at High Risk of Coronary Heart Disease Events In a randomized, double-blind, placebo-controlled, multi-centered study [the Scandinavian Simvastatin Survival Study (Study 4S)], the effect of therapy with simvastatin on total mortality was assessed in 4,444 adult patients with CHD (history of angina and/or a previous myocardial infarction) and baseline total cholesterol (total-C) between 212 and 309 mg/dL who were on a lipid-lowering diet.

The recommended statin therapy for patients at increased risk of cardiovascular events is:

• Simvastatin: for adults with established coronary heart disease, with a dose of 20-40 mg/day.
• Rosuvastatin: for 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. Key points to consider:
• CV risk factors: age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor.
• Dose and administration: simvastatin 20-40 mg/day, rosuvastatin dose not specified in the label. 2 3

From the Research

Statin Therapy for Patients at Increased Risk of Cardiovascular Events

The recommended statin therapy for patients at increased risk of cardiovascular events is a topic of ongoing research and debate. Several studies have compared the efficacy and safety of different statins in this population.

• Rosuvastatin vs. Atorvastatin: A study published in 2006 compared the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia 4. The results showed that rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6. Another study published in 2007 compared rosuvastatin versus atorvastatin in South-Asian patients at risk of coronary heart disease and found that rosuvastatin 10 mg decreased LDL cholesterol by 45% compared to 40% with atorvastatin 10 mg 5.
• High-Intensity Statin Therapy: A study published in 2018 compared the clinical impact of more-intensive vs. less-intensive LDL-C lowering by means of statins and non-statin medications in secondary prevention 6. The results showed that more-intensive treatment was associated with a 19% relative risk reduction for major vascular events. A study published in 2020 compared the safety of high-intensity atorvastatin (40 to 80 mg) with rosuvastatin (20 to 40 mg) in the veteran population and found that high-intensity atorvastatin was associated with an increased incidence of adverse drug reactions compared to rosuvastatin 7.
• Long-Term Efficacy and Safety: A study published in 2007 assessed the long-term efficacy and safety of rosuvastatin 40 mg in patients with severe hypercholesterolemia 8. The results showed that rosuvastatin 40 mg was safe and effective in reducing LDL-C levels and increasing HDL-C levels over a period of 96 weeks.

Key Findings

• Rosuvastatin 10 mg may be more effective than atorvastatin 20 mg in reducing LDL-C levels in high-risk patients with hypercholesterolemia 4, 5.
• High-intensity statin therapy may be associated with an increased incidence of adverse drug reactions compared to less-intensive therapy 7.
• Long-term treatment with rosuvastatin 40 mg is safe and effective in patients with severe hypercholesterolemia 8.
• More-intensive LDL-C lowering by means of statins and non-statin medications may be associated with a reduced risk of major vascular events in secondary prevention 6.