Effects of combination therapy with celecoxib and doxycycline on neointimal hyperplasia and inflammatory biomarkers in coronary artery disease patients treated with bare metal stents

Won Ho Kim, Young Guk Ko, Ki Woon Kang, Jung Sun Kim, Byung Keuk Kim, Donghoon Choi, Myeong Ki Hong, Yangsoo Jang

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3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)68-75
Number of pages8
JournalYonsei medical journal
Volume53
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

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Celecoxib
Doxycycline
Hyperplasia
Stents
Coronary Artery Disease
Biomarkers
Metals
Matrix Metalloproteinase 9
Therapeutics
CD40 Ligand
Matrix Metalloproteinase Inhibitors
Cyclooxygenase 2 Inhibitors
Cyclooxygenase 2
C-Reactive Protein
Thrombosis
Anti-Inflammatory Agents
Myocardial Infarction

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "Effects of combination therapy with celecoxib and doxycycline on neointimal hyperplasia and inflammatory biomarkers in coronary artery disease patients treated with bare metal stents",
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.",
author = "Kim, {Won Ho} and Ko, {Young Guk} and Kang, {Ki Woon} and Kim, {Jung Sun} and Kim, {Byung Keuk} and Donghoon Choi and Hong, {Myeong Ki} and Yangsoo Jang",
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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, Won Ho; Ko, Young Guk; Kang, Ki Woon; Kim, Jung Sun; Kim, Byung Keuk; Choi, Donghoon; Hong, Myeong Ki; Jang, Yangsoo.

In: Yonsei medical journal, Vol. 53, No. 1, 01.01.2012, p. 68-75.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of combination therapy with celecoxib and doxycycline on neointimal hyperplasia and inflammatory biomarkers in coronary artery disease patients treated with bare metal stents

AU - Kim, Won Ho

AU - Ko, Young Guk

AU - Kang, Ki Woon

AU - Kim, Jung Sun

AU - Kim, Byung Keuk

AU - Choi, Donghoon

AU - Hong, Myeong Ki

AU - Jang, Yangsoo

PY - 2012/1/1

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N2 - 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.

AB - 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.

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