A Cochrane review included 15 studies with a total of 3 718 subjects with intermittent claudication secondary to peripheral arterial disease (PAD). Included studies compared cilostazol with placebo or pentoxifylline. Treatment durations ranged from 6 to 26 weeks. For 8 studies data were compatible for comparison by meta-analysis, but data for 7 studies were too heterogenous to be pooled.
There was an improvement in initial claudication distance (ICD - the distance walked on a treadmill before the onset of calf pain) in the cilostazol group for the 100 mg (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; 6 studies, n=1 533) and 50 mg (WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; 2 studies, n=602) twice daily, compared with placebo. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; 8 studies, n=2 247) and 50 mg (WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; 2 studies, n=602) twice daily, compared with placebo. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise confidence interval (WMD 13.42 metres, 95% CI -43.51 to 70.35 metres).
Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; 3 studies, n=894). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no difference in all-cause mortality between the treatment groups, but there were very few events. Only one study evaluated cardiovascular events, and there was no clear difference between any of the treatment groups and risk of myocardial infarction or stroke.
Reviewing the results of the studies not included in the meta-analysis showed a less clear result, with a variability of positive and negative data regarding cilostazol and its effects on ICD and ACD.
Cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations.
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and blinding), and by inconsistency (variability in results). Cilostazol is contraindicated in patients with congestive cardiac failure due to its mechanism of action as a phosphodiesterase III inhibitor. Cilostazol is also contraindicated in patients with moderate to severe renal or hepatic impairment .