Reply: Intriguing Off-Target Effects of Ezetimibe.


Tsujita et al. (1) report patients randomized to atorvastatin þ ezetimibe therapy experienced a greater reduction in the percentage of atheroma volume than those randomized to atorvastatin, and it may be due to the lower mean low-density lipoprotein cholesterol achieved. However, Crea and Niccoli (2) argued and hypothesized that cholesterol lowering itself does not seem to explain the greater reduction in the percentage of atheroma volume with convincing and intriguing pleiotropic effects of ezetimibe. Statins are very important to prevent cardiovascular events in patients at high risk, but dose-dependently worsen insulin sensitivity and increase the risk of type 2 diabetes (3). In addition to lowering LDL cholesterol further, ezetimibe reduced visceral fat with beneficial effects on adiponectin and insulin resistance. Indeed, experimental studies demonstrated that ezetimibe improves liver steatosis and insulin sensitivity in a rat model of metabolic syndrome. We observed that ezetimibe combined with simvastatin significantly decreased insulin levels and increased adiponectin levels and insulin sensitivity and reduced visceral fat and blood pressure quite differently from simvastatin alone in patients with hypercholesterolemia (4). Indeed, a randomized clinical trial demonstrated that simvastatin combined with ezetimibe therapy wasmore beneficial in patients with diabetes than in patients without diabetes (p interaction 1⁄4 0.023) (5). These may in part explain the results of the IMPROVE-IT (Examining Outcomes in Subjects with Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) Versus Simvastatin (P04103) and PRECISE-IVUS (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) studies.

DOI: 10.1016/j.jacc.2015.09.091

Cite this paper

@article{Tsujita2015ReplyIO, title={Reply: Intriguing Off-Target Effects of Ezetimibe.}, author={Kenichi Tsujita and Seigo Sugiyama and Hideki Shimomura and Kenshi Yamanaga and Koichi Kaikita and Seiji Hokimoto and Hisao Ogawa}, journal={Journal of the American College of Cardiology}, year={2015}, volume={66 24}, pages={2808-2809} }