Aortic Aneurysm

A Randomised Placebo-controlled Double-blind Trial to Evaluate Lipid-lowering Pharmacotherapy on Proteolysis and Inflammation in Abdominal Aortic Aneurysms

Dawson JA, Choke E, Loftus IM, et al (St George’s Hosp, London, UK) Eur J Vasc Endovasc Surg 41:28–35, 2011^§

Abstract

Objectives

Modulation of abdominal aortic aneurysm (AAA) expansion by HMG-CoA reductase inhibitors (statins) might be linked to reducing IL-6 and MMP-9, which may be consequent on reducing plasma cholesterol. Ezetimibe is a novel cholesterol absorption inhibitor used in combination with statins. This pilot study compared the biological effects of ezetimibe combination therapy with simvastatin alone on parameters relevant to aneurysm expansion including cytokines and proteolytic enzymes.

Design

Randomised placebo-controlled double-blind trial.

Materials & Methods

Eighteen patients scheduled for elective open AAA repair were randomised to simvastatin 40 mg plus ezetimibe 10 mg (n = 9), or simvastatin 40 mg plus placebo (n = 9), for 32.5 days (IQR 28−50.5) until the day of surgery. Total concentrations of TNF-α, IL-1β, IL-6, IL-8, IL-10, MMPs-1, -2, -3, -8, -9, -12, -13, TIMP-1 and -2 were measured in plasma, aortic wall homogenates and tissue culture explants.

Results

Two patients in the placebo arm did not undergo open repair precluding aortic samples. Ezetimibe was associated with a significant reduction in aortic wall MMP-9 (p = 0.02) and aortic wall IL-6 (p = 0.02), associated with a reduction in plasma lipids.

Conclusions

These results suggest that ezetimibe combination therapy reduces aortic wall proteolysis and inflammation, key processes that drive AAA expansion. A larger RCT is justified focussing on aneurysm growth rates in small AAA (Figs 2 and 3).

Figure 2 Box and whisker plot representing aortic wall MMP-9 in the ezetimibe and placebo groups. Whiskers represent data within 1.5 IQR of the lower and upper quartiles. Mild outliers are represented by dots. (Reprinted from European Journal of Vascular and Endovascular Surgery, Dawson JA, Choke E, Loftus IM, et al. A randomised placebo-controlled double-blind trial to evaluate lipid-lowering pharmacotherapy on proteolysis and inflammation in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2011;41:28–35. Copyright 2011, with permission from the European Society for Vascular Surgery.)

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