Yonsei Med J.  2012 Jan;53(1):68-75. 10.3349/ymj.2012.53.1.68.

Effects of Combination Therapy with Celecoxib and Doxycycline on Neointimal Hyperplasia and Inflammatory Biomarkers in Coronary Artery Disease Patients Treated with Bare Metal Stents

• Kim WH
• Ko YG
• Kang KW
• Kim JS
• Kim BK
• Choi D
• Hong MK
• Jang Y

• KMID: 1779688
• DOI: http://doi.org/10.3349/ymj.2012.53.1.68

Abstract

PURPOSE
Cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 play a key role in the pathogenesis of in-stent restenosis. We investigated the effect of a short-term therapy of celecoxib, a COX-2 inhibitor, with or without doxycycline, an MMP inhibitor, after coronary stenting on inflammatory biomarkers and neointimal hyperplasia.
MATERIALS AND METHODS
A total of 75 patients (86 lesions) treated with bare metal stents were randomized into three groups: 1) combination therapy (200 mg celecoxib and 20 mg doxycycline, both twice daily), 2) celecoxib (200 mg twice daily) only, and 3) non-therapy control. Celecoxib and doxycycline were administered for 3 weeks after coronary stenting. The primary endpoint was neointimal volume obstruction by intravascular ultrasound (IVUS) at 6 months. The secondary endpoints included clinical outcomes, angiographic data, and changes in blood levels of inflammatory biomarkers.
RESULTS
Follow-up IVUS revealed no significant difference in the neointimal volume obstruction among the three treatment groups. There was no difference in cardiac deaths, myocardial infarctions, target lesion revascularization or stent thrombosis among the groups. Blood levels of high-sensitivity C-reactive protein, soluble CD40 ligand, and MMP-9 varied widely 48 hours and 3 weeks after coronary stenting, however, they did not show any significant difference among the groups.
CONCLUSION
Our study failed to demonstrate any beneficial effects of the short-term therapy with celecoxib and doxycycline or with celecoxib alone in the suppression of inflammatory biomarkers or in the inhibition of neointimal hyperplasia. Large scale randomized trials are necessary to define the role of anti-inflammatory therapy in the inhibition of neointimal hyperplasia.

Keyword

Celecoxib; coronary artery disease; coronary stent; neointimal hyperplasia; inflammation

MeSH Terms

Aged
Angioplasty, Balloon, Coronary
Anti-Bacterial Agents/therapeutic use
Biological Markers/metabolism
Coronary Artery Disease/immunology/metabolism/*therapy
Cyclooxygenase 2 Inhibitors/therapeutic use
Doxycycline/*therapeutic use
Drug Therapy, Combination
Female
Follow-Up Studies
Humans
Male
Metals
Middle Aged
Neointima/*drug therapy/*immunology/metabolism
Pyrazoles/*therapeutic use
Stents/*adverse effects
Sulfonamides/*therapeutic use

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