The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]

Michel Le May,Alexander Kulik,Marc Ruel,George A Wells,Thierry G Mesana

doi:10.1186/1468-6708-6-15

Abstract

BackgroundSaphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery.MethodsPatients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.DiscussionThis trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients.

Highlights

Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery
Sample Size The trial will be powered to test the hypothesis that clopidogrel and aspirin should reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery
Subgroup analyses of previous trials have suggested a benefit of clopidogrel in cardiac surgery patients [39,42,43], no trial to date has focused on the clinical or angiographic outcomes in patients treated with clopidogrel therapy immediately after surgical revascularization

Summary

Introduction

Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. The goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery. Coronary artery bypass graft surgery (CABG) is the most durable approach for the treatment of ischemic heart disease [1], with >400,000 procedures performed annually in the United States alone [2]. Despite the increasing application of arterial conduits during CABG, the saphenous vein remains the most common conduit, employed for more than 70% of grafts [3]. Either reoperation or percutaneous coronary intervention, is required in 4% of patients by 5 years, 19% of patients by 10 years and 31% of patients by 12 years after the initial bypass surgery [3,16]

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