What is the recommended treatment for high-risk patients to lower cholesterol levels and reduce cardiovascular events using statins (HMG-CoA reductase inhibitors)?

From the Guidelines

For high-risk patients, intensive statin therapy is recommended to lower cholesterol levels and reduce cardiovascular events. High-intensity statins such as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily should be prescribed to achieve at least a 50% reduction in LDL cholesterol, as supported by the 2017 AHA/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction 1. The Cholesterol Treatment Trialists conducted meta-analyses of individual participant data from randomized trials of more versus less intensive statin regimens, demonstrating that more intensive regimens produced a highly significant 15% further reduction in major vascular events 1.

Key Considerations

• Moderate-intensity options include atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, or pravastatin 40-80 mg daily, which typically reduce LDL by 30-50% 1.
• Treatment should be lifelong for most high-risk patients, including those with established atherosclerotic cardiovascular disease, diabetes with target organ damage, familial hypercholesterolemia, or multiple risk factors.
• Regular monitoring of liver function tests at baseline, 4-12 weeks after initiation, and periodically thereafter is important, as recommended by the 2018 cholesterol clinical practice guidelines 1.
• Patients should be counseled about potential muscle pain and advised to report symptoms promptly.

Additional Therapy for Very High-Risk Patients

• For patients at very high risk for ASCVD, the guideline recommends an LDL-C threshold of 1.8 mmol/L (70 mg/dL) as reasonable for adding a nonstatin medication (ezetimibe or proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) to maximally tolerated statin therapy 1.
• Addition of ezetimibe or PCSK9 inhibitors can reduce risk for subsequent ASCVD events by about 2 percentage points and 15%, respectively 1.

Mechanism of Action

• Statins work by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, which leads to increased LDL receptor expression on hepatocytes and enhanced clearance of LDL from circulation 1.
• This mechanism not only lowers LDL cholesterol but also reduces inflammation and improves endothelial function, providing benefits beyond simple cholesterol reduction.

From the FDA Drug Label

Rosuvastatin tablets are an HMG Co-A reductase inhibitor (statin) indicated: 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. reduce LDL-C and slow the progression of atherosclerosis in adults. reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH) As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia.

The recommended treatment for high-risk patients to lower cholesterol levels and reduce cardiovascular events using statins (HMG-CoA reductase inhibitors) is to use rosuvastatin tablets as an adjunct to diet. The dosage range is 5 mg to 40 mg once daily for adults. Key considerations include:

• CV risk factors: age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor.
• LDL-C reduction: in adults with primary hyperlipidemia, heterozygous familial hypercholesterolemia (HeFH), and homozygous familial hypercholesterolemia (HoFH).
• Atherosclerosis progression: slowing the progression in adults.
• Special populations: dosage adjustments for pediatric patients, Asian patients, and patients with severe renal impairment 2.

From the Research

Statin Treatment for High-Risk Patients

The recommended treatment for high-risk patients to lower cholesterol levels and reduce cardiovascular events using statins (HMG-CoA reductase inhibitors) involves:

• High-intensity statins for patients with atherosclerotic cardiovascular disease (ASCVD) or high-risk patients without clinical ASCVD 3
• A goal of low-density lipoprotein cholesterol reduction of 50% or greater for patients with ASCVD 3
• Consideration of nonstatin drugs (ezetimibe with or without bile acid sequestrant or bempedoic acid and/or a proprotein convertase subtilisin/kexin type 9 inhibitor) for patients with ASCVD at very high risk 3

Alternative Treatment Options

For patients who cannot tolerate high-intensity statins, alternative options include:

• Combining a moderate-intensity statin with ezetimibe 3, 4
• Using proprotein convertase subtilisin/kexin type 9 inhibitors to lower low-density lipoprotein cholesterol levels substantially and reduce risk 3
• Lipoprotein apheresis for high-risk patients with multiple cardiovascular events and sub-optimal LDL cholesterol despite lipid-lowering drug therapy 5

Considerations for Statin Selection

When selecting a statin, considerations include:

• Efficacy for reducing cardiovascular risk and safety in specific clinical settings 6
• Pharmacokinetics, safety, drug metabolism, and interactions to minimize side effects and improve compliance 6
• Individualization of statin treatment based on specific diseases and patient characteristics 6