Do statins improve organ function and decrease blood vessel narrowing through mechanisms other than lowering low-density lipoprotein (LDL) cholesterol in patients with coronary artery disease (CAD) and cerebral small vessel ischemia?

From the Guidelines

Statins improve organ function and decrease blood vessel narrowing through mechanisms beyond LDL cholesterol reduction in patients with coronary artery disease and cerebral small vessel ischemia, and should be continued even if LDL levels are < 1.8 mmol/L, as their benefits extend beyond cholesterol lowering. These additional benefits, known as pleiotropic effects, include improving endothelial function, reducing inflammation, stabilizing atherosclerotic plaques, decreasing oxidative stress, and inhibiting blood clot formation 1. Statins like atorvastatin and rosuvastatin enhance nitric oxide production, which improves blood vessel dilation and blood flow, and reduce inflammatory markers such as C-reactive protein 1.

When explaining to a patient with evidence of CAD and small cerebral vessel ischemia on a statin, who wants to try a diet-controlled route only, it's essential to emphasize that statins provide benefits beyond just lowering LDL cholesterol, including reducing the risk of major vascular events by approximately 15% in patients with CAD, as shown in the CTT meta-analysis 1. The patient should be informed that discontinuing statin treatment can lead to increased total and cardiovascular mortality, as well as cardiovascular morbidity 1.

Some key points to discuss with the patient include:

• The importance of continuing statin therapy to achieve desired LDL-C goals and reduce the risk of major vascular events
• The benefits of statins in improving endothelial function, reducing inflammation, and stabilizing atherosclerotic plaques
• The potential risks of discontinuing statin treatment, including increased mortality and morbidity
• The role of lifestyle changes, such as dietary intervention, in combination with statin therapy to achieve optimal lipid control and reduce cardiovascular risk.

It's also important to note that the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline recommends high-intensity statin regimens for patients with CAD, and that the benefits of high-intensity statins appear early after ACS and persist over time, independent of baseline LDL-C concentration 1.

From the Research

Statins and Organ Function

• Statins have been shown to improve organ function and decrease blood vessel narrowing through mechanisms other than lowering low-density lipoprotein (LDL) cholesterol, including stabilization of plaque and potentially pleiotropic effects 2.
• The clinical significance of intensive lipid-lowering therapy using statins has been discussed in relation to large-scale clinical trials, plaque regression and stabilization, and diverse effects of statins 3.

Statins and Cerebral Small Vessel Ischemia

• Statin intervention studies have demonstrated a decrease in the risk of stroke in patients with atherosclerosis of other territories and a decrease in all cardiovascular events in patients who have had a stroke 2.
• The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial demonstrated the benefit of high doses of atorvastatin in the secondary prevention of ischemic stroke 2.
• However, national guidelines recommend statins for patients with acute cerebral ischemia (ACI) of large or small vessel atherosclerotic origin and without these stroke mechanisms but coexisting coronary artery disease or primary prevention indications 4.

Explaining Statin Therapy to Patients

• When explaining statin therapy to a patient with evidence of CAD and small cerebral vessel ischemia on a statin, who wants to try a diet-controlled route only since their LDL is < 1.8 with a low-dose statin, it is essential to discuss the benefits of statin therapy in reducing cardiovascular events and the potential risks of discontinuing therapy 5, 4.
• Patients with cerebral small vessel ischemia may be at higher risk for cardiovascular events, and statin therapy may be beneficial in reducing this risk 2.
• However, it is also important to consider the potential adverse effects of statin therapy, particularly in patients without indications for statins, and to weigh the benefits and risks of therapy on an individual basis 4, 6.