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Home > Vascular Annual Meeting > RR1. Pre-operative Use of Clopidogrel...

RR1. Pre-operative Use of Clopidogrel and Aspirin vs. Aspirin Is Associated with a Stable Atherosclerotic Plaque Phenotype

Wouter Peeters1,2, Gerard Pasterkamp2, Dominique de Kleijn2, Jean-Paul de Vries3, Frans Moll1
1Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, Netherlands; 2Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, Netherlands; 3Department of Vascular Surgery, St. Antonius Hospital, Nieuwegein, Netherlands

OBJECTIVES: Thrombocyte-aggregation-inhibitors (TAI) exert beneficial effects in patients with significant carotid stenosis or symptomatic lesions on peri-operative and clinical outcome during follow up. However it is still unclear how TAIs exert their effects and if dual therapy is more opportune. Inflammation within the plaque is the main feature determining vulnerability and local restenosis. Besides the primary effects of TAIs on platelets, anti-inflammatory effects have been described, which may support plaque stability. For clinical perspectives, this could have beneficial effects on peri-operative morbidity and clinical outcome during follow up. This study compares the effects of preoperative TAIs with a combination on atherosclerotic plaque phenotype as a determinant for vulnerability.

METHODS: Atherosclerotic plaques from 104 patients have been harvested during carotid endarterectomy. Patients were stratified regarding preoperative TAI-use; 1) no TAI, 2) Aspirin, 3), Aspirin and Clopidogrel. Plaques were assessed for macrophage infiltration, smooth muscle cell (SMC) content and lipid core size as measures for plaque stability. Biomarker levels of IL4, IL6, IL8, IL10 were determined as measures of the inflammatory status at protein level. The groups were age and gender matched and individual data regarding cardiovascular risk factors, clinical status and medication use were analyzed to exclude confounding.

RESULTS: Pre-operative TAI-use is associated with reduced macrophage (p<0.001) and increased SMC (p=0.03) infiltration. The combination of Aspirin and Clopidogrel had additional effects on macrophage and SMC infiltration compared to Aspirin. On biomarker level, increased levels of anti-inflammatory IL4 (p=0.02) and IL10 were observed in the combination group compared to Aspirin. Inflammatory IL8 levels showed an evident tendency of reduction in the Aspirin group and even more in the combination group.

CONCLUSIONS: The combination of Aspirin and Clopidogrel has beneficial effects on the inflammatory status compared to Aspirin alone, indicating that it supports plaque stability. The outcome of this study may be a reason to study the effects of combination therapy on peri-operative morbidity, local restenosis and clinical outcome in a longitudinal trial following carotid surgery.

AUTHOR DISCLOSURES: W. Peeters, None; G. Pasterkamp, None; D. de Kleijn, None; J. de Vries, None; F. Moll, None.