Oral Anticoagulant and Antiplatelet Therapy for Peripheral Arterial Disease: A Meta-analysis of Randomized Controlled Trials

Peripheral artery disease (PAD) is a common disease affecting over 200 million people worldwide. PAD is associated with significant limb and cardiovascular morbidity and mortality which is reduced by antiplatelet and antithrombotic therapy. However, the optimal type, dose, and time of antithrombotic therapy is still uncertain.We searched 4 electronic databases from January 1, 1990, to June 1, 2020, for randomized controlled trials of patients who received oral anticoagulant and antiplatelet therapy for PAD. The primary outcome was a composite of acute limb ischemia, major amputation, myocardial infarction, ischemic stroke, death from cardiovascular events, or death from any cause. Secondary outcomes included major bleeding, fatal bleeding, and intracranial hemorrhage events.We identified 3 studies that satisfied inclusion and exclusion criteria. Compared with antiplatelet alone, oral anticoagulant plus antiplatelet therapy improved acute limb ischemia (p < 0.00001), stroke (p = 0.005), and major amputation events (p = 0.11). However, oral anticoagulant plus antiplatelet therapy was not effective for prevention of myocardial infarction (p = 0.23), death from cardiovascular events (p = 0.65), or death from any cause (p = 0.66). Additionally, a significant increase in major bleeding events was demonstrated (p < 0.00001). There was no significant difference in fatal bleeding (p = 0.16) or intracranial hemorrhage events (p = 0.43). This meta-analysis showed that oral anticoagulant plus antiplatelet therapy for PAD may improve acute limb ischemia and major amputation or stroke risk compared with antiplatelet therapy alone, but could increase the risk of major bleeding events. On the other hand, measuring myocardial infarction, death, fatal bleeding, or intracranial hemorrhage risk remains controversial.