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Evidence summaries

Cilostazol for Peripheral Arterial Disease

Cilostazol may improve walking distance compared with placebo in people with stable intermittent claudication secondary to peripheral arterial disease. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 16 studies with a total of 3 972 subjects with stable intermittent claudication secondary to peripheral arterial disease (PAD). Included studies compared cilostazol with placebo or pentoxifylline. Treatment durations ranged from 6 to 26 weeks. Cilostazol dose ranged from 100 mg to 300 mg, and pentoxifylline dose ranged from 800 mg to 1200 mg.

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 (MD 26.49 metres, 95% CI 18.93 to 34.05 metres; 6 studies, n=1 722) compared with placebo. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol (MD 39.57 metres, 95% CI 21.80 to 57.33 metres, statistical heterogeneity I2 =62%; 8 studies, n=2 360) compared with placebo. The most commonly reported adverse events were headache, diarrhoea, abnormal stools, dizziness, pain and palpitations. Cilostazol increased the risk of headache compared to placebo (OR 2.83, 95% CI 2.26 to 3.55; 8 studies, n=2 584). Conclusions on revascularisation, amputation, or cardiovascular events could not be made.

There was no difference between cilostazol and pentoxifylline for improving ICD (MD 20.0 metres, 95% CI -2.57 to 42.57; 1 study, n=417) or ACD (MD 13.4 metres, 95% CI -43.50 to 70.36, statistical heterogeneity I2 =90%; 2 studies, n=866). No study reported on revascularisation, amputation or cardiovascular events. Cilostazol increased headache compared with pentoxifylline at 24 weeks (OR 2.20, 95% CI 1.16 to 4.17, statistical heterogeneity I2 =69%; 2 studies, n=982).

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and blinding), and by suspected publication bias (pharmaceutical sponsors involved in all studies). Cilostazol is contraindicated in patients with heart failure due to its mechanism of action as a phosphodiesterase III inhibitor. 2.

References

  • Brown T, Forster RB, Cleanthis M et al. Cilostazol for intermittent claudication. Cochrane Database Syst Rev 2021;(6):CD003748. [PubMed]
  • Chapman TM, Goa KL. Cilostazol: a review of its use in intermittent claudication. Am J Cardiovasc Drugs 2003;3(2):117-38. [PubMed]

Primary/Secondary Keywords