Does adding an oral anticoagulant improve outcomes for patients with peripheral arterial disease?

Adding an oral anticoagulant to antiplatelet therapy in patients with lower extremity vascular disease or carotid artery disease does not improve cardiovascular outcomes and is associated with a significant increase in major bleeding. (LOE = 1b)

The Warfarin Antiplatelet Vascular Evaluation Trial Investigators, Anand S, Yusuf S, et al. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 2007;357:217-227.  [PMID:17634457]

Randomized controlled trial (nonblinded)

Government

Concealed

Outpatient (any)

Although antiplatelet therapy is routinely recommended for patients with peripheral arterial disease, it is unknown whether adding an oral anticoagulant would improve outcomes. These researchers identified 2417 adults between the ages of 35 years and 85 years with documented symptomatic lower extremity vascular disease or carotid artery disease (recent transient ischemic attack or stroke, carotid endarterectomy, or carotid stenosis > 50%). Patients were then given an antiplatelet agent (aspirin, ticlopidine, or clopidogrel at the discretion of their treating physician) and an oral anticoagulant (warfarin in 5 countries, acenocoumarol in 2 countries) for a 2-week to 4-week run-in period. The 2161 who were compliant, agreed to continue, and achieved a stable international normalized ratio between 2.0 and 3.0 were randomized with concealed allocation to receive either antiplatelet therapy alone or antiplatelet therapy plus oral anticoagulation. The patients' mean age was 64 years, 74% were men, and 82% had lower extremity vascular disease. Participants were followed for an average of 3 years, and although patients and physicians were not masked, outcomes were assessed by an independent team masked to treatment assignment. There was no difference between groups in either of the 2 composite outcomes ([1]myocardial infarction, stroke, or cardiovascular death, or [2] myocardial infarction, stroke, severe coronary or peripheral ischemia, or cardiovascular death). However, there were more episodes of life-threatening bleeding (4.0% vs 1.2%; P < .001; number needed to treat to harm [NNTH] = 36) or moderate bleeding (2.9% vs 1.0%; P = .002; NNTH = 53) in the oral anticoagulant group.