Effect on platelet function of cilostazol, clopidogrel, and aspirin, each alone or in combination

Management of peripheral arterial disease (PAD) requires standard atherosclerotic risk management interventions. However, PAD is often complicated by walking pain (intermittent claudication [IC]), which requires symptom-specific therapies as well. Thus, all PAD patients are encouraged to take antiplatelet agents to reduce the associated risks of major cardiovascular events, and those with IC may also require treatment with cilostazol, an agent proven to increase exercise capacity and enhance quality of life in these patients. Although it was initially thought that cilostazol's antiplatelet properties might render it unsafe to use in combination with other platelet inhibitors because of possible additive effects, a recent study has dispelled such concerns. There is evidence that in a crossover trial of 21 patients with PAD and IC, aspirin alone, or clopidogrel alone, significantly increased bleeding times, but cilostazol alone did not. The combination of aspirin and clopidogrel had a greater effect on increasing bleeding time than either monotherapy, and no further bleeding time prolongation was observed, when cilostazol was added to any aspirin/clopidogrel regimen. These findings suggest that PAD patients with IC may be safely managed with both cilostazol and standard antiplatelet therapy, without increasing the risk of adverse bleeding effects.