Prolonged application of clopidogrel reduces inflammation after percutaneous coronary intervention in the porcine model☆

Abstract 

Objective

We determined the effect of prolonged treatment with clopidogrel on C-reactive protein (CRP) concentrations and blood thrombogenicity after percutaneous transluminal coronary angioplasty followed by intracoronary brachytherapy in the porcine model.

Animal model

All 48 pigs received antiplatelet therapy, including aspirin (325 mg, daily) and clopidogrel (300 mg, loading dose) 1 day before PCI, followed by a daily dose of clopidogrel (75 mg/day) in addition to aspirin. During PCI, one of two balloon-injured arteries was randomly assigned to receive immediate radiation treatment. Animals were sacrificed after 24 h, 1 month, and 3 months post-PCI. The pigs, which were sacrificed 3 months post-PCI, were divided into two groups. The first group received clopidogrel in addition to aspirin for 3 months, and the second group received clopidogrel in addition to aspirin for only 1 month after PCI and then aspirin alone.

Methods

Blood was taken from all pigs before intervention, immediately after intervention, and before sacrifice. Serum CRP was measured by enzyme-linked immunosorbent assay. To analyze the procoagulant effects of PCI on blood thrombogenicity, a one-stage clotting assay was performed.

Results

Clopidogrel treatment for 3 months reduced CRP levels more than did clopidogrel therapy for 1 month only at 3 months post-PCI (27.9±3.9 vs. 56.6±11.3 μg/ml; P=.019). Baseline CRP levels were found to be 50.4±4.8 μg/ml. Plasma clotting was not affected by prolonged clopidogrel therapy (322.8±59.3 s vs. 295.2±52.5 s; P=ns).

Conclusions

Prolonged treatment with clopidogrel reduced CRP levels post-PCI.

Keywords: Clopidogrel, C-reactive protein, Inflammation, Percutaneous coronary intervention, Procoagulability