Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: Results of the CEZAR study

Ostad, Mir Abolfazl; Eggeling, Silke; Tschentscher, Peter; Schwedhelm, Edzard; Böger, Rainer; Wenzel, Philip; Meinertz, Thomas; Munzel, Thomas; Warnholtz, Ascan

doi:10.1016/j.atherosclerosis.2008.11.032

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Volume 205, Issue 1 , Pages 227-232, July 2009

Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: Results of the CEZAR study

Mir Abolfazl Ostad
- Department of Medicine II, Johannes Gutenberg-University Mainz, Germany
Silke Eggeling
- University Heart Center, Department of Cardiology, Hamburg, Germany
Peter Tschentscher
- University Hospital Hamburg-Eppendorf, Department of Clinical Chemistry, University of Hamburg, Germany
Edzard Schwedhelm
- University Hospital Hamburg-Eppendorf, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Hamburg, Germany
Rainer Böger
- University Hospital Hamburg-Eppendorf, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Hamburg, Germany
Philip Wenzel
- Department of Medicine II, Johannes Gutenberg-University Mainz, Germany
Thomas Meinertz
- University Heart Center, Department of Cardiology, Hamburg, Germany
Thomas Munzel
- Department of Medicine II, Johannes Gutenberg-University Mainz, Germany
Ascan Warnholtz
- Department of Medicine II, Johannes Gutenberg-University Mainz, Germany
- Corresponding author at: II. Medizinische Klinik, Klinikum der Johannes Gutenberg-Universität Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. Tel.: +49 6131 17 3746; fax: +49 6131 17 6428.

Received 19 September 2008; received in revised form 26 October 2008; accepted 10 November 2008. published online 16 January 2009.

Abstract

Background

Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction.

Methods and results

Fifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent vasodilation (NMD), lipid, C-reactive protein (CRP) plasma concentrations and urinary 8-iso-prostaglandin F2alpha excretion were measured before and after treatment. Total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10. A80 caused significantly stronger improvement of FMD compared to A10E10 (absolute change FMD: A80+2.7±3.0% (post vs. pre p<0.001), A10E10+0.6±2.9% (post vs. pre p=0.25), A80 vs. A10E10 p=0.018). NMD was improved by A80 but not by A10E10 (absolute change NMD: A80+2.7±4.6%, A10E10+0.7±3.5%, p=0.12). Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostaglandin F2alpha excretion. There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group.

Conclusions

The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms, LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD.

Keywords: Brachial artery, Endothelium, Ezetimibe, Flow-mediated dilation, Statin