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Increased Restenosis Rate After Implantation of Drug-Eluting Stents in Patients With Elevated Serum Activity of Matrix Metalloproteinase-2 and -9

Katharina M. Katsaros, MD^_*, Stefan P. Kastl, MD^_*, Gerlinde Zorn, BSci^_*, Gerald Maurer, MD^_*, Johann Wojta, PhD^_*, Kurt Huber, MD^,_*, Günter Christ, MD^_*, Walter S. Speidl, MD^_*

^_* Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
Third Department of Medicine, Wilhelminen Hospital, Vienna, Austria

^_* Reprint requests and correspondence: Dr. Kurt Huber, Director, Third Medical Department, Cardiology and Emergency Medicine, Wilhelminen Hospital, Montleartstrasse 37, A-1160 Vienna, Austria (Email: kurt.huber{at}wienkav.at).

Objectives: Our aim was to test whether serum levels of matrix metalloproteinase (MMP)-2 and -9 are associated with the development of in-stent restenosis (ISR) after implantation of drug-eluting stents (DES).

Background: With the introduction of DES coronary ISR could be reduced dramatically. However, it still plays a significant role, particularly after treatment of multiple, complex lesions.

Methods: We studied 85 patients who were treated with 159 DES. Blood samples for measurement of MMP-2 and -9 antigen and activity were taken directly before and 24 h after percutaneous coronary intervention (PCI). Restenosis was evaluated at 6 to 8 months by coronary angiography.

Results: During the follow-up period, 2 patients (2.4%) died of cardiovascular causes, and 12 patients developed angiographic ISR. Patients with ISR showed significantly higher serum activity of MMP-9 at baseline (p = 0.017) and of MMP-2 (p < 0.0001) and MMP-9 (p < 0.0001) after the procedure. The PCI increased serum activity of MMP-2 (p = 0.005) and MMP-9 (p = 0.008) only in patients with ISR. The restenosis rates of patients in the highest quartile of MMP-2 after and MMP-9 before and after PCI were 40.0%, 38.9%, and 42.9% compared with 6.3%, 7.7%, and 4.0% in the lower quartiles, respectively. This was independent of clinical and procedural characteristics.

Conclusions: Elevated serum activities of MMP-2 and -9 are associated with dramatically increased restenosis rates after PCI with implantation of DES. Determination of MMP levels might be useful for identification of patients who are at high risk for ISR despite implantation of DES.

Key Words: angioplasty • drug-eluting stents • restenosis • metalloproteinases

Abbreviations and Acronyms   BMS = bare-metal stent(s)   DES = drug-eluting stent(s)   ISR = in-stent restenosis   MMP = matrix metalloproteinase   PCI = percutaneous coronary intervention   PES = paclitaxel-eluting stent(s)   SES = sirolimus-eluting stent(s)

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