Systematic review of the efficacy of cilostazol, naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication

• Published in: British journal of surgery Vol. 99; no. 12; pp. 1630 - 1638
• Main Authors: Stevens, J. W., Simpson, E., Harnan, S., Squires, H., Meng, Y., Thomas, S., Michaels, J., Stansby, G.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-12-2012; Wiley; Oxford University Press
• Subjects: Biological and medical sciences; General aspects; Humans; Intermittent Claudication - drug therapy; Intermittent Claudication - etiology; Intermittent Claudication - physiopathology; Medical sciences; Miscellaneous; Nafronyl - therapeutic use; Pain - prevention & control; Pentoxifylline - therapeutic use; Peripheral Vascular Diseases - complications; Peripheral Vascular Diseases - physiopathology; Public health. Hygiene; Public health. Hygiene-occupational medicine; Randomized Controlled Trials as Topic; Tetrazoles - therapeutic use; Treatment Outcome; Vasodilator Agents - therapeutic use; Walking - physiology; Claudication; 3',5'-Cyclic-nucleotide phosphodiesterase; Vasodilator agent; Enzyme; Oxalate; Treatment efficiency; Evidence-based practice; Enzyme inhibitor; Systematic review; Esterases; Cilostazol; Phosphoric diester hydrolases; Evidence-based medicine; Phosphodiesterase inhibitor; Naftidrofuryl; Pentoxifylline; Treatment; Intermittent; Surgery; Hydrolases; Xanthine derivatives; Fibrinolytic; Bibliographic review
• ISSN: 0007-1323; 1365-2168
• DOI: 10.1002/bjs.8895

Background:
A systematic review and network meta‐analysis was undertaken to consider the evidence for the efficacy and tolerability of placebo, cilostazol, naftidrofuryl oxalate and pentoxifylline in patients with intermittent claudication due to peripheral arterial disease (PAD).
Methods:
MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings, BIOSIS, National Research Register and MetaRegister databases were searched. Eligible studies were randomized controlled trials (RCTs) and published systematic reviews of patients with intermittent claudication due to PAD and whose symptoms persisted despite a period of conservative management. Study selection was conducted by one reviewer with involvement from a clinician. Data were extracted by one reviewer with no blinding to authors or journal, and checked by a second reviewer. Outcome measures were maximum walking distance (MWD) and pain‐free walking distance (PFWD).
Results:
The review identified 1876 citations; 26 RCTs met the inclusion criteria for the systematic review. Eleven trials provided data relevant for the meta‐analysis. Naftidrofuryl oxalate was ranked first for both MWD and PFWD (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. For naftidrofuryl oxalate, cilostazol and pentoxifylline, MWD increased by 60 (95 per cent credible interval 20 to 114) per cent, 25 (11 to 40) per cent and 11 (−1 to 24) per cent respectively relative to placebo, and PFWD increased by 49, 13 and 9 per cent.
Conclusion:
Naftidrofuryl oxalate and cilostazol are both effective treatments for claudication; naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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