Clinical study
A comparison of cilostazol and pentoxifylline for treating intermittent claudication

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Abstract

PURPOSE: We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline.

PATIENTS AND METHODS: We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks.

RESULTS: Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups.

CONCLUSION: Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects.

Section snippets

Material and methods

Design of this trial followed the recommendations of the Society for Vascular Surgery for trials of medications treating intermittent claudication (7). The study was conducted under an Investigational New Drug Exemption with approval of each of the 54 participating institutions’ human subjects review committees and the written informed consent of each participant.

Patients with stable, moderate-to-severe symptoms of intermittent claudication were studied. Symptoms must have been present for at

Results

We screened 922 consenting patients, of whom 699 (76%) met the inclusion criteria and were randomly assigned to one of the three treatments (Figure 1). One patient withdrew before taking the first drug dose, leaving 698 patients who could be evaluated. There were no statistically significant differences in the baseline characteristics of the three groups (Table 1). Of the 698 patients who started treatment, 159 (23%) withdrew from the study before the last visit (week 24). Withdrawal rates

Discussion

Standard medical management of patients with intermittent claudication from atherosclerotic peripheral artery disease includes a walking exercise program, smoking cessation, antiplatelet therapy, treatment of atherosclerosis risk factors, evaluation for associated cardiovascular disease (such as coronary artery disease), and, in some patients, drug treatment for symptomatic relief. Surgical or endovascular intervention is usually reserved for patients with severe, lifestyle-limiting symptoms

Acknowledgements

The following institutions and persons contributed to the Claudication Treatment Study. Wilford Hall Medical Center: DL Dawson; University of Massachusetts Medical Center: BS Cutler; Jobst Vascular Center: HG Beebe; Baylor College of Medicine: JA Herd; Chicago Center for Clinical Research: M Davidson; Jacksonville Cardiovascular Clinic: DA Chinoy; Ochsner Clinic: SR Money; University of Colorado Health Sciences Center: JG Regensteiner; Definitive Health: T Bajwa; University of Virginia: DW

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    Supported by Otsuka America Pharmaceuticals, Inc., a US affiliate of the manufacturer of cilostazol. The views expressed herein are those of the authors and do not reflect the official policy of the Department of Defense, the Department of Veterans Affairs, or other departments of the United States government.

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