This systematic review conducted by researchers with the NHS Health Technology Assessment (HTA) programme examined the clinical- and cost-effectiveness of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for intermittent claudication in people with peripheral arterial disease whose symptoms continue despite a period of conventional management.

A search for literature carried out between April to June 2010 identified 26 RCTs that met the inclusion criteria for the clinical effectiveness review. The following findings were reported:

• There was evidence that walking distance outcomes were significantly improved by both cilostazol and naftidrofuryl oxalate;

• It was not possible to include inositol nicotinate within the meta-analysis of maximal walking distance (MWD) and pain-free walking distance (PFWD) owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect.

• Adverse events were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome.

• Health-related quality of life data were limited.

• Two studies of limited quality were identified within the review of cost-effectiveness: the de novo model developed suggests that naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100 to £500 per year for the other drugs).

This review concluded from these data that “naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty.”