Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.
OBJECTIVE
Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting.


METHODS
Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification).


RESULTS
In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P(interaction) = .008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%).


CONCLUSIONS
The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk.
Belch
Jill J F
JJ
Institute of Cardiovascular Research, Ninewells Hospital, Dundee, UK. J.J.F.Belch@dundee.ac.uk
Dormandy
John
J
Biasi
G M
GM
Biasi
B M
BM
Cairols
M
M
Diehm
C
C
Eikelboom
B
B
Golledge
J
J
Jawien
A
A
Lepäntalo
M
M
Norgren
L
L
Hiatt
W R
WR
Becquemin
J P
JP
Bergqvist
D
D
Clement
D
D
Baumgartner
I
I
Minar
E
E
Stonebridge
P
P
Vermassen
F
F
Matyas
L
L
Leizorovicz
A
A
D000368:Aged; D000671:Amputation, Surgical; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000401:mortality; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D015990:Placebo Effect; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012086:Reoperation; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014654:Vascular Patency; D014680:Veins / Q000637:transplantation*
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin