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

From the Guidelines

High-intensity statin therapy is recommended for patients with established atherosclerotic cardiovascular disease or those at high risk for cardiovascular events, as it reduces major cardiovascular events by 21% for every 39 mg/dL of LDL cholesterol lowering, as shown in the Cholesterol Treatment Trialists’ Collaboration 1. The most commonly prescribed high-intensity statins are atorvastatin 40-80mg daily and rosuvastatin 20-40mg daily, which work by inhibiting HMG-CoA reductase, resulting in significant reductions in LDL cholesterol levels (typically 50% or greater) 2. Some key points to consider when prescribing high-intensity statins include:

• Monitoring for side effects, including muscle pain or weakness, which occurs in approximately 5-10% of patients 3
• Checking liver function tests at baseline and as clinically indicated 2
• Advising patients that the full lipid-lowering effect typically takes 4-6 weeks to develop, and regular follow-up is important to ensure medication adherence and monitor for potential side effects 2
• Considering the addition of ezetimibe or a PCSK9 inhibitor if the LDL cholesterol goal of <55 mg/dL is not achieved on maximum tolerated statin therapy 1 High-intensity statins are indicated for secondary prevention in patients with established atherosclerotic cardiovascular disease, including those with prior heart attacks, strokes, or coronary interventions, as well as for primary prevention in patients with very high LDL levels (≥190 mg/dL) or diabetes with multiple risk factors 3. The benefits of high-intensity statin therapy have been consistently shown in multiple large randomized trials, including the Cholesterol Treatment Trialists’ Collaboration, which involved 26 statin trials and showed a significant reduction in major cardiovascular events in people with diabetes for every 39 mg/dL of LDL cholesterol lowering 1.

From the FDA Drug Label

12.1 Mechanism of Action Rosuvastatin is an inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. 12.2 Pharmacodynamics Inhibition of HMG-CoA reductase by rosuvastatin accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol.

The effect of high-intensity statin (HMG-CoA reductase inhibitor) therapy, such as rosuvastatin, is to decrease plasma LDL-C and total cholesterol by inhibiting the production of cholesterol in the liver and increasing the uptake of LDL-C from the blood to the liver. 4

From the Research

Effect of High-Intensity Statin Therapy

• High-intensity statin therapy is associated with a reduced risk of major adverse cardiovascular events in patients with clinical atherosclerotic cardiovascular disease (ASCVD) or at high risk of ASCVD 5, 6
• The use of high-intensity statins, such as atorvastatin 40 to 80 mg and rosuvastatin 20 to 40 mg, has been shown to be effective in reducing low-density lipoprotein cholesterol (LDL-C) levels and improving cardiovascular outcomes 7, 6
• However, high-intensity statin therapy has also been linked to an increased incidence of adverse drug reactions (ADRs), including abnormal liver transaminases and statin-associated muscle symptoms 5

Comparison of High-Intensity Statins

• Atorvastatin 80 mg has been shown to be more effective than simvastatin 80 mg in reducing LDL-C levels and improving cardiovascular outcomes 7
• Rosuvastatin 40 mg has been found to be one of the most potent statins in reducing LDL-C levels, with a reduction of up to 48.2% 8
• The ranking of statins by potency is rosuvastatin, atorvastatin, and simvastatin, although at maximum dosage, atorvastatin and rosuvastatin are nearly equivalent 8

Real-World Use of High-Intensity Statins

• Despite the benefits of high-intensity statin therapy, many patients at high cardiovascular risk are not receiving adequate treatment, with only 15.0% of patients initiating therapy with a high-intensity statin 9
• Patients who initiate treatment with a high-intensity statin regimen have a longer duration of treatment and higher proportion of days covered (PDC) compared to those who initiate treatment with a moderate- to low-intensity statin regimen 9
• However, even among patients who receive high-intensity statin therapy, there is still a significant risk of cardiovascular events, highlighting the need for ongoing monitoring and optimization of treatment 9