6.1 Intermittent claudication

A meta-analysis of randomised trials of antiplatelet therapy has shown a reduction in the risk of cardiovascular events in patients with peripheral arterial disease, usually intermittent claudication (absolute risk difference 1.2% over one year) ⁷ (see Table 1). Reduction in progression of atherosclerosis has been shown in randomised controlled angiographic studies.⁸ A reduction in the risk of peripheral arterial surgery in patients receiving aspirin therapy was a retrospective observation of a randomised study.^{115, 116} A large randomised controlled trial including patients with peripheral arterial disease has shown increased efficacy and similar safety of clopidogrel versus aspirin.⁹³ Evidence level Ia and Ib

Patients with intermittent claudication should receive aspirin (75-300 mg/day) long term as prophylaxis of cardiovascular events.

(See SIGN guideline on Drug Therapy for Peripheral Vascular Disease.¹¹⁷)

Clopidogrel (75 mg/day) is an effective alternative in patients with contraindications to aspirin, or who are intolerant of aspirin.

The role of long term oral anticoagulants is uncertain: further trials are in progress.¹¹⁸

6.2 Critical limb ischaemia and amputation

Hospitalised patients who are immobilised with chronic critical limb ischaemia, including those who have undergone amputation, are at high risk of thromboembolism. Extrapolation of results from other patient groups⁵ and the opinion of a consensus group¹¹⁹ suggests that such patients should receive anticoagulant prophylaxis for venous thromboembolism. Evidence level III and IV

Hospitalised patients with chronic critical limb ischaemia should receive prophylaxis for venous thromboembolism with either subcutaneous low dose standard heparin (5,000 IU 8 hourly) or adjusted-dose warfarin (target therapeutic range of INR 2.0-3.0).5

In patients with acute critical ischaemia, full-dose intravenous heparin (target APTT ratio 2.0, range 1.5-2.5) is standard practice.116

6.2.1 PERIPHERAL ARTERIAL EMBOLISM AND ATRIAL FIBRILLATION

In patients with peripheral arterial embolism and atrial fibrillation or other cardiac source of embolism, long-term prophylaxis with warfarin (target INR 2.5, range 2.0-3.0) is recommended. (See sections 3 and 4.)

6.2.2 LOCAL THROMBOLYTIC THERAPY

In selected patients with acute critical limb ischaemia, overviews of the results of randomised trials suggest that thrombolysis may be an alternative to surgery.^{28, 29, 116, 119, 120, 121, 122, 123} Evidence level Ib

In patients with acute critical limb ischaemia, local thrombolytic therapy should be considered.

6.3 Peripheral angioplasty and bypass grafts

It is standard practice to give intravenous heparin during peripheral angioplasty, and to heparinise systemically during bypass graft surgery.116

Meta-analyses of randomised controlled trials of postoperative antiplatelet agents, including aspirin, have shown improved synthetic graft patency. The evidence for benefit from antiplatelet agents when native graft material is used is not available. Antiplatelet agents, including aspirin, have been shown to improve arterial patency in patients with peripheral arterial disease, as well as reducing cardiovascular events.^{7, 8, 9, 116} Evidence level Ia

Aspirin (300 mg/day) should be given as antithrombotic prophylaxis of cardiovascular events, starting 6 hours following angioplasty or bypass grafting and continued long-term (75-300 mg/day).

Clopidogrel (75 mg/day) is an effective alternative treatment for long term prophylaxis in selected patients who are intolerant of aspirin.

There is insufficient evidence to support routine long-term anticoagulation in patients with infra-inguinal grafts or angioplasty.^{116, 118}