What is the effect of high-intensity statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

High intensity statins should be prescribed to patients with acute coronary syndromes to reduce major vascular events by approximately 15% compared to moderate-intensity statins, as evidenced by the CTT meta-analysis 1. The benefit of high-intensity statin regimens is well-established, with a significant reduction in cardiovascular and all-cause death, as demonstrated in the A to Z and PROVE IT-TIMI 22 trials 1. Key points to consider when prescribing high intensity statins include:

• High-intensity statin regimens lower LDL-C concentration by an average of ≥50% 1
• The two main high intensity statins are atorvastatin (Lipitor) at doses of 40-80mg daily and rosuvastatin (Crestor) at doses of 20-40mg daily 1
• Patients should take high intensity statins at the same time each day, preferably in the evening for atorvastatin and any time of day for rosuvastatin
• Common side effects include muscle pain, liver enzyme elevations, and slightly increased risk of diabetes
• Baseline liver function tests and periodic monitoring are recommended
• Patients should avoid grapefruit juice with atorvastatin and report any unexplained muscle pain, tenderness, or weakness The 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline recommends high-intensity statin therapy for patients with acute coronary syndromes, as it provides a significant reduction in major vascular events 1. In clinical practice, high intensity statins have been shown to be effective in reducing cardiovascular risk, and their use is supported by the latest clinical guidelines 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. As an adjunct to diet to: reduce LDL-C in adults with primary hyperlipidemia.

The high intensity statin is rosuvastatin, which is indicated for:

• Reducing the risk of major adverse cardiovascular events in adults without established coronary heart disease
• Reducing LDL-C in adults with primary hyperlipidemia
• Reducing LDL-C and slowing the progression of atherosclerosis in adults
• Reducing LDL-C in adults and pediatric patients with heterozygous familial hypercholesterolemia (HeFH) 2
• Reducing LDL-C in adults and pediatric patients with homozygous familial hypercholesterolemia (HoFH) Key points about rosuvastatin include:
• It is an HMG Co-A reductase inhibitor (statin)
• It is used as an adjunct to diet to reduce LDL-C in various patient populations Note that the dosing for high intensity statin therapy is not explicitly defined in the provided drug labels, and the specific dosing for rosuvastatin can be found in the dosage and administration section of the drug label 2

From the Research

High-Intensity Statin Therapy

• High-intensity statins are recommended for patients with atherosclerotic cardiovascular disease (ASCVD) and high-risk patients without clinical ASCVD 3
• The goal of high-intensity statin therapy is to achieve a low-density lipoprotein cholesterol (LDL-C) reduction of 50% or greater 3
• High-risk primary prevention patients who may benefit from high-intensity statin therapy 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 3

Combination Therapy with Ezetimibe

• Adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin monotherapy can provide greater reduction in LDL-C levels compared to doubling the initial statin dose 4, 5, 6
• Combination therapy with ezetimibe and a statin can be considered for patients who do not achieve target LDL-C levels with statin monotherapy 5, 6
• Rosuvastatin/ezetimibe is a potent and generally well-tolerated drug combination for the management of primary hypercholesterolemia in adults 4

Treatment Strategies

• A treat-to-target strategy, where the goal is to achieve a specific LDL-C level, may be noninferior to a high-intensity statin strategy for long-term clinical outcomes in patients with coronary artery disease 7
• High-intensity statin therapy can be considered as an initial treatment strategy for patients with coronary artery disease, with the goal of achieving at least a 50% reduction in LDL-C 7
• The choice of treatment strategy should be individualized based on patient characteristics and response to therapy 7