Trial of Clopidogrel After Surgery for Coronary Artery Disease (CASCADE Trial)

Summary

The purpose of this study is to determine whether the combination of clopidogrel with aspirin prevents the development of blockages (atherosclerosis) in vein grafts one year after coronary artery bypass surgery (CABG) compared to aspirin alone.

Timeline

Start

2006-05

Primary completion

2009-06

Completion

2009-07

Publications

• Background Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am Coll Cardiol. 1996 Sep;28(3):616-26. doi: 10.1016/0735-1097(96)00206-9.
• Background Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation. 1998 Mar 10;97(9):916-31. doi: 10.1161/01.cir.97.9.916.
• Background Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes AW. Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest. 1992 Feb;89(2):507-11. doi: 10.1172/JCI115613.
• Background Herbert JM, Dol F, Bernat A, Falotico R, Lale A, Savi P. The antiaggregating and antithrombotic activity of clopidogrel is potentiated by aspirin in several experimental models in the rabbit. Thromb Haemost. 1998 Sep;80(3):512-8.
• Background Herbert JM, Tissinier A, Defreyn G, Maffrand JP. Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits. Arterioscler Thromb. 1993 Aug;13(8):1171-9. doi: 10.1161/01.atv.13.8.1171.
• Background Hermann A, Weber AA, Schror K. Clopidogrel inhibits platelet adhesion and platelet-dependent mitogenesis in vascular smooth muscle cells. Thromb Res. 2002 Jan 15;105(2):173-5. doi: 10.1016/s0049-3848(01)00403-0. No abstract available.
• Background Harker LA, Marzec UM, Kelly AB, Chronos NR, Sundell IB, Hanson SR, Herbert JM. Clopidogrel inhibition of stent, graft, and vascular thrombogenesis with antithrombotic enhancement by aspirin in nonhuman primates. Circulation. 1998 Dec 1;98(22):2461-9. doi: 10.1161/01.cir.98.22.2461.
• Background Cadroy Y, Bossavy JP, Thalamas C, Sagnard L, Sakariassen K, Boneu B. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans. Circulation. 2000 Jun 20;101(24):2823-8. doi: 10.1161/01.cir.101.24.2823.
• Background Bhatt DL, Chew DP, Hirsch AT, Ringleb PA, Hacke W, Topol EJ. Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation. 2001 Jan 23;103(3):363-8. doi: 10.1161/01.cir.103.3.363.
• Background Fox KA, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ, Yusuf S; Clopidogrel in Unstable angina to prevent Recurrent ischemic Events Trial. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation. 2004 Sep 7;110(10):1202-8. doi: 10.1161/01.CIR.0000140675.85342.1B. Epub 2004 Aug 16.
• Results Kulik A, Le May M, Wells GA, Mesana TG, Ruel M. The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]. Curr Control Trials Cardiovasc Med. 2005 Oct 11;6(1):15. doi: 10.1186/1468-6708-6-15.
• Results Kulik A, Le May MR, Voisine P, Tardif JC, Delarochelliere R, Naidoo S, Wells GA, Mesana TG, Ruel M. Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) Trial. Circulation. 2010 Dec 21;122(25):2680-7. doi: 10.1161/CIRCULATIONAHA.110.978007. Epub 2010 Dec 6.
• Results Kulik A, Voisine P, Mathieu P, Masters RG, Mesana TG, Le May MR, Ruel M. Statin therapy and saphenous vein graft disease after coronary bypass surgery: analysis from the CASCADE randomized trial. Ann Thorac Surg. 2011 Oct;92(4):1284-90; discussion 1290-1. doi: 10.1016/j.athoracsur.2011.04.107.
• Results Une D, Kulik A, Voisine P, Le May M, Ruel M. Correlates of saphenous vein graft hyperplasia and occlusion 1 year after coronary artery bypass grafting: analysis from the CASCADE randomized trial. Circulation. 2013 Sep 10;128(11 Suppl 1):S213-8. doi: 10.1161/CIRCULATIONAHA.112.000328.
• Results Une D, Al-Atassi T, Kulik A, Voisine P, Le May M, Ruel M. Impact of clopidogrel plus aspirin versus aspirin alone on the progression of native coronary artery disease after bypass surgery: analysis from the Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) randomized trial. Circulation. 2014 Sep 9;130(11 Suppl 1):S12-8. doi: 10.1161/CIRCULATIONAHA.113.008227.
• Hage A, Voisine P, Erthal F, Larose E, Glineur D, Chow B, Tremblay H, Fortier J, Ko G, Une D, Farkouh M, Mesana TG, LeMay M, Kulik A, Ruel M. Eight-year follow-up of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial. J Thorac Cardiovasc Surg. 2018 Jan;155(1):212-222.e2. doi: 10.1016/j.jtcvs.2017.06.039. Epub 2017 Jun 24.

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