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: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Ko
authors.forename: Ki Woon
authors.initials: KW
authors.lastname: Kang
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Byung-Keuk
authors.initials: BK
authors.lastname: Kim
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.forename: Myeong-Ki
authors.initials: MK
authors.lastname: Hong
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D000068579:Celecoxib; D003324:Coronary Artery Disease / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004318:Doxycycline / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008670:Metals; D008875:Middle Aged; D058426:Neointima / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D015607:Stents / Q000009:adverse effects*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D008670:Metals; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D004318:Doxycycline