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Effect of Cilostazol on Treadmill Walking, Community-Based Walking Ability, and Health-Related Quality of Life in Patients with Intermittent Claudication Due to Peripheral Arterial Disease: Meta-Analysis of Six Randomized Controlled Trials


  • Dr. Judith Regensteiner has been on the speakers' bureau of Otsuka America, Pharm. Dr. Walter McCarthy has no relationship to Otsuka America. Dr John Ware has been an occasional consultant (unpaid) to Otsuka America. Dr. William Hiatt has been on a steering committee and speakers bureau of Otsuka America. Drs. William Forbes and Peter Forbes and Mr. Jeffrey Heckman work for Otsuka America.

Address correspondence to Judith G. Regensteiner, PhD, Section of Vascular Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box B-180, Denver, CO 80262. E-mail:


OBJECTIVES: To assess whether cilostazol, a phosphodiesterase III inhibitor, improves treadmill and community-based walking ability and health-related quality of life (HQL) in patients with intermittent claudication resulting from peripheral arterial disease (PAD).

DESIGN: Retrospective meta-analysis of data pooled from six Phase 3, multicenter, double-blind, placebo-controlled, parallel-group, randomized studies.

SETTING: Patients were recruited from outpatient ambulatory medical care facilities.

PARTICIPANTS: Patients' (n = 1,751) mean age ± standard deviation was 65 ± 9, and they had a history of PAD for 6 months or longer and an ankle brachial index (ABI) of 0.90 or less.

INTERVENTION: Cilostazol 50 mg bid or 100 mg bid for 12, 16, or 24 weeks.

MEASUREMENTS: ABI; maximal walking distance (MWD); pain-free walking distance on a graded and constant-load treadmill; and HQL, measured using the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study Short Form-36 (SF-36).

RESULTS: Maximal treadmill walking distance improved more in both cilostazol groups than in the placebo group (both P < .0001). WIQ and SF-36 physical summary scores improved significantly more with cilostazol than with placebo (for instance, WIQ distance score, P < .0001 and SF-36 physical summary score, P < .0001, comparing persons taking cilostazol with controls). Improved MWD correlated with improvements in WIQ (correlation with distance score, r = 0.34, P < .0001) and SF-36 physical summary scores (r = 0.29, P < .0001).

CONCLUSIONS: Treatment with cilostazol was associated with greater improvements in community-based walking ability and HQL in patients with intermittent claudication than treatment with placebo. These improvements correlated with increased MWD. This analysis of effects of cilostazol on improving walking ability in persons with claudication is the first cilostazol study focused on community-based measures of functional status and HQL. Questionnaires assessing walking ability and HQL provide important patient-based information about clinical outcomes of claudication therapy.