Table 4.

Recommendations for Antiplatelet and Antithrombotic Drugs

2005 Recommendations	2011 Focused Update Recommendations	Comments
Class I
Antiplatelet therapy is indicated to reduce the risk of MI, stroke, or vascular death in individuals with atherosclerotic lower extremity PAD. (Level of Evidence: A)	1. Antiplatelet therapy is indicated to reduce the risk of MI, stroke, and vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia (43–45). (Level of Evidence: A)	Modified recommendation (wording clarified).
Aspirin, in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in individuals with atherosclerotic lower extremity PAD. (Level of Evidence: A)	2. Aspirin, typically in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia (44,45). (Level of Evidence: B)	Modified recommendation (wording clarified; and level of evidence changed from A to B).
Clopidogrel (75 mg per day) is recommended as an effective alternative antiplatelet therapy to aspirin to reduce the risk of MI, stroke, or vascular death in individuals with atherosclerotic lower extremity PAD. (Level of Evidence: B)	3. Clopidogrel (75 mg per day) is recommended as a safe and effective alternative antiplatelet therapy to aspirin to reduce the risk of MI, ischemic stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia (43). (Level of Evidence: B)	Modified recommendation (wording clarified).
Class IIa
	1. Antiplatelet therapy can be useful to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with an ABI less than or equal to 0.90 (45). (Level of Evidence: C)	New recommendation
Class IIb
	1. The usefulness of antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with borderline abnormal ABI, defined as 0.91 to 0.99, is not well established (46,47). (Level of Evidence: A)	New recommendation
	2. The combination of aspirin and clopidogrel may be considered to reduce the risk of cardiovascular events in patients with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia and who are not at increased risk of bleeding and who are at high perceived cardiovascular risk (48,49). (Level of Evidence: B)	New recommendation
Class III: No benefit
Oral anticoagulation therapy with warfarin is not indicated to reduce the risk of adverse cardiovascular ischemic events in individuals with atherosclerotic lower extremity PAD. (Level of Evidence: C)	1. In the absence of any other proven indication for warfarin, its addition to antiplatelet therapy to reduce the risk of adverse cardiovascular ischemic events in individuals with atherosclerotic lower extremity PAD is of no benefit and is potentially harmful due to increased risk of major bleeding (50). (Level of Evidence: B)	Modified recommendation (level of evidence changed from C to B).

ABI indicates ankle-brachial index; MI, myocardial infarction; and PAD, peripheral artery disease.