Increased restenosis rate after implantation of drug-eluting stents in patients with elevated serum activity of matrix metalloproteinase-2 and -9.
OBJECTIVE
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.
Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Katharina M
KM
Katsaros
Stefan P
SP
Kastl
Gerlinde
G
Zorn
Gerald
G
Maurer
Johann
J
Wojta
Kurt
K
Huber
Günter
G
Christ
Walter S
WS
Speidl
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation*; D002317:Cardiovascular Agents / Q000008:administration & dosage; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000201:enzymology / Q000628:therapy*; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000201:enzymology / Q000209:etiology*; D054855:Drug-Eluting Stents; D006801:Humans; D016015:Logistic Models; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D016017:Odds Ratio; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D002317:Cardiovascular Agents; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017239:Paclitaxel; D020123:Sirolimus