Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) Trial.
BACKGROUND
clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound.


RESULTS
in this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1 ± 2.0 versus 4.5 ± 2.1 mm(2), aspirin-clopidogrel versus aspirin-placebo, P=0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group (P=0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group (P=0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9 ± 3.4% in the aspirin-clopidogrel group and 91.1 ± 3.8% in the aspirin-placebo group (P=0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P=0.50).


CONCLUSIONS
compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting.
Lynn Heart and Vascular Institute, University of Ottawa Heart Institute, Ontario, Canada.
Alexander
A
Kulik
Michel R
MR
Le May
Pierre
P
Voisine
Jean-Claude
JC
Tardif
Robert
R
Delarochelliere
Sarika
S
Naidoo
George A
GA
Wells
Thierry G
TG
Mesana
Marc
M
Ruel
D000368:Aged; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D000077144:Clopidogrel; D001026:Coronary Artery Bypass / Q000379:methods*; D003324:Coronary Artery Disease / Q000601:surgery*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D006801:Humans; D006965:Hyperplasia / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012501:Saphenous Vein / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D018084:Ultrasonography, Interventional
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin