(Circulation. 2008;118:S_905.)
© 2008 American Heart Association, Inc.
Peripheral Arterial Disease Therapeutics |
1 Univ of Edinburgh, Edinburgh, United Kingdom
2 The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
3 Vascular Surgery, Edinburgh, United Kingdom
4 The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
5 Univ of Edinburgh, Edinburgh, United Kingdom
Patients with critical limb ischaemia have a peri-operative cardiovascular morbidity comparable to patients with an acute coronary syndrome. We hypothesised that peri-operative dual antiplatelet therapy would improve biomarkers of atherothrombosis without causing unacceptable bleeding in patients undergoing surgery for critical limb ischaemia. In a prospective double-blind randomised controlled trial, 108 patients undergoing infra-inguinal revascularisation or amputation for critical limb ischaemia were maintained on aspirin (75 mg daily) and randomised 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. Clopidogrel caused a reduction in platelet-monocyte aggregation (30% versus 38%; P=0.007) that was sustained in the post-operative period (P=0.0019). There were 18 troponin-positive events (16.0% clopidogrel versus 17.2% placebo; OR 0.91, 95% CI 0.39 to 2.17; P=0.86) with clopidogrel causing a greater decline in troponin concentrations (P<0.001). There was no increase in major life-threatening (14% versus 10%; OR 1.4, 95% CI 0.44 to 4.5; P=0.56), minor bleeding (34% versus 21%; OR 1.9, 95% CI 0.8 to 4.7; P=0.12), although red blood cell transfusions (SIGN criteria) were increased (28% versus 12%; OR 2.8, 95% CI 1.1 to 7.7; P=0.037). In patients with critical limb ischaemia, peri-operative dual anti-platelet therapy has beneficial effects on reducing biomarkers of atherothrombosis without increasing life-threatening bleeds. Large-scale randomised controlled trials are needed to establish whether dual antiplatelet therapy improves clinical outcome in high-risk patients undergoing vascular surgery.
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