Dual Lipid-Lowering Strategy and Coronary Plaque Regression

Study Questions:

What are the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients undergoing percutaneous coronary intervention (PCI)?

Methods:

PRECISE-IVUS (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) was a prospective, randomized, controlled, multicenter trial. Eligible patients undergoing PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) <70 mg/dl. Serial volumetric intravascular ultrasound was performed at baseline and again at 9-12 months to quantify the coronary plaque response in 202 patients.

Results:

The combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p < 0.001). For the absolute change in percent atheroma volume (PAV), the mean difference between the two groups (-1.538%; 95% confidence interval, -3.079% to 0.003%) did not exceed the predefined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual lipid-lowering strategy (-1.4% [-3.4% to -0.1%] vs. -0.3% [-1.9% to 0.9%] with atorvastatin alone; p = 0.001). For PAV, a significantly greater percentage of patients receiving atorvastatin/ezetimibe showed coronary plaque regression (78% vs. 58%; p = 0.004). Both strategies had acceptable side-effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events.

Conclusions:

The authors concluded that compared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression.

Perspective:

This study reports that a dual lipid-lowering strategy combining atorvastatin and ezetimibe resulted in more remarkable reduction of LDL-C than atorvastatin monotherapy, and volumetric IVUS analysis demonstrated superiority regarding coronary plaque regression with negative vascular remodeling in the analyzed target segment. Furthermore, significant favorable effect of the dual lipid-lowering strategy on the coronary atherosclerotic development was noted, especially in the acute coronary syndrome cohort, along with a reduction of cholesterol absorption markers and lower LDL-C levels. Combination therapy with statin plus ezetimibe appears to be a promising lipid-lowering option, particularly for high-risk patients.

Keywords: Acute Coronary Syndrome, Anticholesteremic Agents, Atherosclerosis, Cholesterol, Cholesterol, LDL, Coronary Artery Disease, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipoproteins, LDL, Percutaneous Coronary Intervention, Plaque, Atherosclerotic, Primary Prevention, Ultrasonography, Interventional


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