A new pharmacological treatment for intermittent claudication: Results of a randomized, multicenter trial

Background: Effective medication is limited for the relief of intermittent claudication, a common manifestation of arterial occlusive disease. Cilosta zol is a potent inhibitor of platelet aggregation with vasodilation effects . Objective: To evaluate the safety and efficacy of cilostazol for the treatm ent of intermittent claudication. Methods: Thirty-seven outpatient vascular medicine clinics at regional tert iary and university hospitals in the United States participated in this mul ticenter, randomized, double-blind, placebo-controlled, parallel trial. Of the 663 screened volunteer patients with leg discomfort, a total of 516 men and women 40 years or older with a diagnosis of moderately severe chronic, stable, symptomatic intermittent claudication were randomized to receive c ilostazol, 100 mg, cilostazol, 50 mg, or placebo twice a day orally for 24 weeks. Outcome measures included pain-free and maximal walking distances vi a treadmill testing, patient-based quality-of-life measures, global assessm ents by patient and physician, and cardiovascular morbidity and all-cause m ortality survival analysis. Results: The clinical and statistical superiority of active treatment over placebo was evident as early as week 4, with continued improvement at all s ubsequent time points. After 24 weeks, patients who received cilostazol, 10 0 mg, twice a day had a 51% geometric mean improvement in maximal walking d istance (P<.001 vs placebo); those who received cilostazol, 50 mg, twice a day had a 38% geometric mean improvement in maximal walking distance (P<.00 1 vs placebo). These percentages translate into an arithmetic mean increase in distance walked, from 129.7 m at baseline to 258.8 m at week 24 for the cilostazol, 100 mg, group, and from 131.5 to 198.8 m for the cilostazol, 5 0 mg, group. Geometric mean change for pain-free walking distance increased by 59% (P<.001) and 48% (P<.001), respectively, in the cilostazol, 100 mg, and cilostazol, 50 mg, groups. These results were corroborated by the resu lts of subjective quality-of-life assessments, functional status, and globa l evaluations. Headache, abnormal stool samples or diarrhea, dizziness, and palpitations were the most commonly reported potentially drug-related adve rse events and were self-limited. A total of 75 patients (14.5%) withdrew b ecause of any adverse event, which was equally distributed between all 3 tr eatment groups. Similarly, there were no differences between groups in the incidence of combined cardiovascular morbidity or all-cause mortality. Conclusion: Compared with placebo, long-term use of cilostazol, 100 mg or 5 0 mg, twice a day significantly improves walking distances in patients with intermittent claudication.