Randomized controlled trial of dual antiplatelet therapy in patients undergoing surgery for critical limb ischemia.
OBJECTIVE
Patients with critical limb ischemia have a perioperative cardiovascular morbidity comparable to patients with acute coronary syndromes. We hypothesized that perioperative dual antiplatelet therapy would improve biomarkers of atherothrombosis without causing unacceptable bleeding in patients undergoing surgery for critical limb ischemia.


METHODS
In a double-blind randomized controlled trial, 108 patients undergoing infrainguinal revascularization or amputation for critical limb ischemia were maintained on aspirin (75 mg daily) and randomized to clopidogrel (600 mg prior to surgery, and 75 mg daily for 3 days; n = 50) or matched placebo (n = 58). Platelet activation and myocardial injury were assessed by flow cytometry and plasma troponin concentrations, respectively.


RESULTS
Clopidogrel reduced platelet-monocyte aggregation before surgery (38%-30%; P = 0.007). This was sustained in the postoperative period (P = 0.0019). There were 18 troponin-positive events (8 [16.0%] clopidogrel vs. 10 [17.2%] placebo; relative risk [RR]: 0.93, 95% confidence interval [CI]: 0.39-2.17; P = 0.86). Half of troponin-positive events occurred preoperatively with clopidogrel causing a greater decline in troponin concentrations (P < 0.001). There was no increase in major life-threatening bleeding (7 [14%] vs. 6 [10%]; RR: 1.4, 95% CI: 0.49-3.76; P = 0.56) or minor bleeding (17 [34%] vs. 12 [21%]; RR 1.64, 95% CI: 0.87-3.1; P = 0.12), although blood transfusions were increased (28% vs. 12.6%, RR: 2.3, 95% CI: 1.0-5.29; P = 0.037).


CONCLUSIONS
In patients with critical limb ischemia, perioperative dual antiplatelet therapy reduces biomarkers of atherothrombosis without causing unacceptable bleeding. Large-scale randomized controlled trials are needed to establish whether dual antiplatelet therapy improves clinical outcome in high-risk patients undergoing vascular surgery.
Burdess
Anne
A
Departments of Clinical and Surgical Sciences, The University of Edinburgh, Edinburgh, United Kingdom. anne.burdess@ed.ac.uk
Nimmo
Alastair F
AF
Garden
O James
OJ
Murie
John A
JA
Dawson
A Raymond W
AR
Fox
Keith A A
KA
Newby
David E
DE
D000368:Aged; D000671:Amputation, Surgical; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007511:Ischemia / Q000601:surgery*; D007866:Leg / Q000098:blood supply*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014336:Troponin / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D014336:Troponin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin