Do HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins, decrease atherosclerotic plaque deposits?

From the Guidelines

Statins have been shown to delay coronary atherosclerosis progression and possibly induce plaque regression, as evidenced by serial angiographic and intravascular ultrasonographic studies. The mechanism by which statins decrease plaque deposits involves inhibiting the HMG-CoA reductase enzyme, the rate-limiting step in cholesterol biosynthesis, thereby lowering LDL-C levels, with reductions ≥50% observed with high-intensity statin regimens 1.

Key Points to Consider

• High-intensity statin therapy appears to confer incremental clinical benefit compared with less intensive therapy, with a 15% further reduction in major vascular events, driven by reductions in coronary death or non-fatal MI, coronary revascularization, and ischemic stroke 1.
• The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommends treatment of patients ≤75 y of age who have clinical atherosclerotic cardiovascular disease with high-intensity statin 1.
• Statins not only lower LDL ("bad") cholesterol levels but also stabilize existing plaques, making them less likely to rupture and cause heart attacks or strokes, and possess anti-inflammatory properties that help reduce arterial inflammation associated with atherosclerosis.

Clinical Application

• Typical starting doses of statins range from 10-40mg daily, with adjustments based on cholesterol response and side effects.
• For maximum benefit, statins should be taken consistently, usually in the evening for most types, and combined with heart-healthy lifestyle changes including diet modifications, regular exercise, and smoking cessation.
• Regular monitoring of liver function and muscle symptoms is important during statin therapy to check for potential side effects.

From the FDA Drug Label

1. 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. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low-density lipoproteins The maximum LDL-C reduction of rosuvastatin is usually achieved by 4 weeks and is maintained after that.

Statins decrease LDL-C levels, which can lead to a decrease in plaque deposits.

• The mechanism of action of rosuvastatin involves the inhibition of HMG-CoA reductase, leading to a decrease in cholesterol synthesis.
• This decrease in cholesterol synthesis can slow the progression of atherosclerosis, which is the buildup of plaque deposits in the arteries 2.
• The reduction of LDL-C levels can also reduce the risk of major adverse cardiovascular events, including myocardial infarction and stroke 2.

From the Research

Statins and Plaque Deposits

• Statins have been shown to reduce the risk of cardiovascular disease by 24-37% by lowering low-density lipoprotein cholesterol (LDL-C) levels 3.
• The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial found that an intensive lipid-lowering regimen using atorvastatin decreased atherogenic lipoproteins and atheroma volume in patients with established coronary heart disease (CHD), compared with a moderate regimen using pravastatin 3.
• The study also found that there was no measurable atheroma progression in the atorvastatin group, suggesting that statins can help reduce plaque deposits 3.
• Other studies have also found that statins can reduce LDL-C levels and decrease the risk of major cardiovascular events, even in patients with normal LDL-C levels at baseline 4, 3.

Mechanism of Action

• Statins work by inhibiting HMG-CoA reductase, a key enzyme in the synthesis of cholesterol, which leads to a reduction in LDL-C levels 5.
• PCSK9 inhibitors, a new class of lipid-lowering therapies, work by inactivating the liver proprotein convertase subtilisin kexin 9 (PCSK9), which increases the number of LDL receptors available and leads to a profound reduction in circulating LDL particles 6.

Clinical Implications

• The use of statins and other lipid-lowering therapies, such as PCSK9 inhibitors, can help reduce plaque deposits and decrease the risk of cardiovascular disease 3, 6.
• The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend the use of PCSK9 inhibitors in very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 6.