Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease.
OBJECTIVE
This study evaluated the effects of cilostazol on walking distances in patients with intermittent claudication (IC) caused by peripheral arterial occlusive disease.


METHODS
The study was a multicenter, randomized, double-blind, placebo-controlled trial. Two hundred thirty-nine patients with IC were randomly assigned to receive cilostazol (100 mg b.i.d.) or a placebo for 16 weeks. All patients underwent serial, variable-grade, constant-speed treadmill testing. Absolute claudication distance (ACD), assessed at the end of the 12-hour dosing interval (trough), was the primary end point. Secondary end points included ACD assessed 3 to 4 hours after dosing (peak) and initial claudication distances (trough and peak). Functional status measures, including the Medical Outcomes Scale (SF-36) and Walking Impairment Questionnaire, were used to assess subjective changes over the 16-week treatment period. Ankle-brachial indexes were calculated from Doppler-measured systolic pressures at every visit with treadmill testing.


RESULTS
Patients treated with cilostazol demonstrated significant improvements over the placebo patients in ACD at all three time points tested after baseline (weeks 8, 12, and 16). Peak treadmill testing at weeks 8 and 12 also showed significant improvement in walking distances for cilostazol-treated patients over placebo-treated patients. At week 16, patients in the cilostazol group had a 96.4-meter (47%) increase in ACD compared with 31.4 meters (12.9%) for the placebo group (p < 0.001). In the SF-36, significant improvement was observed in the physical component subscale and the composite physical component score. In the Walking Impairment Questionnaire, improvements were significant in patient reports of walking speed and specific measures of walking difficulty. Ankle-brachial indexes improved in the cilostazol group (0.64 +/- 0.02 to 0.70 +/- 0.02) compared with the placebo group (0.68 +/- 0.02 to 0.69 +/- 0.02) (p < 0.0125). The most frequent adverse events were headache, abnormal stools (e.g. loose stools), diarrhea, and dizziness.


CONCLUSIONS
Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.
Money
S R
SR
Ochsner Clinic, New Orleans, La. 70121, USA.
Herd
J A
JA
Isaacsohn
J L
JL
Davidson
M
M
Cutler
B
B
Heckman
J
J
Forbes
W P
WP
D000077407:Cilostazol; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000209:etiology / Q000534:rehabilitation; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000150:complications*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016138:Walking
D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D000077407:Cilostazol