Statins are a class of medications designed primarily to lower cholesterol levels in the blood. The question of whether statins actively reduce atherosclerotic plaque, the fatty deposits that narrow arteries, is complex. Atherosclerosis is the underlying condition where these plaques build up. While statins are highly effective in lowering the risk of heart attacks and strokes, their direct physical effect on the plaque itself is complex. The benefit of statin therapy extends far beyond simply shrinking the lesions, involving structural changes that make existing plaque much safer.
How Statins Affect Cholesterol Metabolism
Statins exert their primary therapeutic effect by targeting a specific step in the liver’s cholesterol production pathway. The drugs act as competitive inhibitors of the enzyme HMG-CoA reductase, which is a rate-limiting step in the synthesis of cholesterol within liver cells. By blocking this enzyme, statins significantly decrease the amount of cholesterol the liver produces internally.
This reduction creates a state of depletion within the liver cells. In response, the cells increase the number of low-density lipoprotein (LDL) receptors on their surface. These upregulated receptors then efficiently pull LDL cholesterol from the bloodstream. This action leads to a substantial decrease in circulating LDL-cholesterol levels, which is the main driver of plaque formation.
High-intensity regimens can achieve LDL-cholesterol reductions of up to 60%. The lowered concentration of circulating cholesterol reduces the supply of material available to form new plaque or expand existing lesions. This metabolic shift promotes stabilization rather than plaque growth.
Plaque Stabilization and Potential for Reduction
The most significant physical benefit of statin therapy on existing plaque is structural stabilization, not volume reduction. Plaques most likely to cause a heart attack or stroke have a large, soft lipid core and a thin, fragile fibrous cap. Statins change the composition of the plaque, making it less prone to rupture.
Treatment with statins, particularly high-dose regimens, helps to strengthen the fibrous cap covering the plaque. Simultaneously, the drugs reduce the size and lipid content of the unstable core within the plaque. This transformation from a “soft” to a “harder” plaque significantly lowers the likelihood of the plaque rupturing and forming a clot.
Statins also possess anti-inflammatory actions, known as pleiotropic effects, separate from their cholesterol-lowering function. Inflammation within the artery wall is a key factor that destabilizes plaque and promotes its growth. By reducing this chronic inflammation, statins help to halt the progression of the disease and contribute to stabilization.
While stabilization is the primary goal, imaging studies using intravascular ultrasound (IVUS) have confirmed that statins can induce a modest physical reduction, or regression, in plaque volume. This regression is typically small, often in the range of a few percent, but it is a measurable effect, particularly in patients who achieve very low LDL-cholesterol levels.
Long-Term Cardiovascular Risk Reduction
The biological effects of statins—lowering systemic cholesterol, stabilizing plaque, and reducing inflammation—translate directly into a profound reduction in major adverse cardiovascular events (MACE). These events include heart attack, stroke, and cardiovascular death. The long-term benefit of statin therapy is consistently demonstrated across many large clinical trials.
For every significant reduction in LDL-cholesterol, there is a corresponding relative reduction in the risk of events. A 39 mg/dL (1 mmol/L) reduction in LDL-C is consistently associated with a relative risk reduction of approximately 21% to 22% for major vascular events. This relative benefit applies across various patient groups, regardless of their initial cholesterol levels.
Absolute risk reduction is the actual difference in the percentage of people who experience an event with or without the drug. For patients with established cardiovascular disease, the absolute reduction in the risk of a major coronary event over five years can be substantial. For high-risk individuals, this can mean a 5-year absolute risk reduction for MACE of around 5.1% to 7.8%.
The benefit of statin therapy is directly proportional to a patient’s baseline cardiovascular risk, meaning those at highest risk gain the greatest absolute benefit. The protective effect of statins is cumulative, with the absolute risk reduction increasing the longer a patient remains on therapy. This sustained reduction in event rates underscores that plaque stabilization is ultimately more important for patient outcomes than achieving a large physical reduction in plaque volume.