Association between the efficacy of dual antiplatelet therapy and the development of in-stent neointimal hyperplasia in porcine coronary arteries.
OBJECTIVE
We set out to compare the effectiveness of platelet aggregation therapy in association with the development of in-stent neointimal hyperplasia in porcine coronary arteries.


METHODS
Thirty-two pigs underwent coronary stenting with bare-metal stents under general anaesthesia. One hundred milligrams of aspirin and loading doses of either 300 mg clopidogrel (group C, n=13) or 2 x 500 mg ticlopidine (group T, n=19) were administered before intervention. During the follow-up, the animals received a daily dose of 100 mg aspirin and 75 mg clopidogrel or 2 x 250 mg ticlopidine, respectively. After 4 weeks, the histopathological and histomorphometric parameters of the explanted stented coronaries were assessed. Levels of circulating cytokines and platelet activation factors were measured. ADP-induced and collagen-induced aggregation was measured immediately before stenting and then every 3rd day. The aggregation profiles were calculated and correlated with the histological parameters.


RESULTS
The fibrin deposition scores and inflammation scores were higher in group T than in group C, with similar injury scores. Endothelialization was complete in both groups. A significantly lower neointimal area (1.08+/-0.36 vs. 1.58+/-0.5, group C vs. T, P=0.026) and percentage of area stenosis (29.8+/-12.1 vs. 44.3+/-16.3, group C vs. T, P=0.032) were observed in group C. The loading dose of clopidogrel significantly reduced the platelet activation parameters before the first angiography as compared with ticlopidone. Clopidogrel treatment resulted in a significantly better aggregation profile relative to ticlopidine (mean ADP-induced aggregation: 28.4+/-9.1 vs. 52.5+/-12.0%, P<0.001). Significant (P<0.05) positive linear correlations were observed between the ADP-induced aggregation profile and the neointimal area (r=0.584), percentage of area stenosis (r=0.666), inflammation (r=0.476) and fibrin deposition (r=0.496).


CONCLUSIONS
The effectiveness of dual antiplatelet therapy plays an important role in the inhibition of in-stent neointimal hyperplasia.
Hemetsberger
Rayyan
R
Department of Cardiology, Medical University of Vienna, Vienna, Austria.
Farhan
Serdar
S
Strehblow
Christoph
C
Sperker
Wolfgang
W
Pavo
Imre
I
Petrasi
Zsolt
Z
Hemetsberger
Hani
H
Posa
Aniko
A
Huber
Kurt
K
Glogar
Dietmar
D
Gyöngyösi
Mariann
M
D000244:Adenosine Diphosphate; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D000077144:Clopidogrel; D003094:Collagen; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005337:Fibrin / Q000378:metabolism; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000097:blood; D008670:Metals; D019007:P-Selectin / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011474:Prosthesis Design; D015607:Stents; D013552:Swine; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D016207:Cytokines; D018836:Inflammation Mediators; D008670:Metals; D019007:P-Selectin; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D005337:Fibrin; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin