Human clinical, pharmacokinetic and randomized comparative trials performed in the US and Asia were reviewed. Selected in vitro, ex vivo, and animal studies were evaluated when human data were not available.
DATA SYNTHESIS:
Intermittent claudication, defined as reproducible discomfort of a muscle group induced by exercise and relieved by rest, is the most common clinical manifestation of
peripheral arterial disease (PAD).
Cilostazol, a specific inhibitor of cyclic
adenosine monophosphate phosphodiesterase in platelets and vascular smooth-muscle cells, is a potent
antiplatelet agent and
vasodilator that reduces vascular proliferation and has
lipid-lowering effects in vivo. Recent multicenter, randomized, placebo-controlled trials have led to approval of
cilostazol by the Food and Drug Administration for relief of
intermittent claudication in patients with stable PAD.
Cilostazol doubled walking distances and improved quality of life compared with placebo in these studies. One trial found that
cilostazol was more effective than
pentoxifylline, the only alternative pharmacologic
therapy for claudication. Although frequent (approximately 50%) minor adverse effects, including
headache,
diarrhea, and palpitations, may occur in clinical practice,
cilostazol has not been associated with major adverse events or increased mortality. Small, nonblind studies suggest that
cilostazol may prove useful in preventing
thrombosis and restenosis following
percutaneous coronary interventions, although these remain unlabeled uses.
CONCLUSIONS: The unique combination of antiplatelet, vasodilatory, and antiproliferative effects of
cilostazol appear to make it an attractive agent for use in patients with PAD. Clinical trials demonstrating a significant improvement in walking distances with
cilostazol therapy suggest that it will be an important tool in improving symptoms and quality of life in patients with
intermittent claudication.