Intravenous naftidrofuryl for critical limb ischaemia.
BACKGROUND
Peripheral arterial disease affects five per cent of men and women by late middle age. Approximately 25% of those affected will develop critical limb ischaemia (rest pain, ulceration and gangrene) within five years. Naftidrofuryl is a vasoactive drug which may be beneficial in the treatment of critical limb ischaemia.


OBJECTIVE
To determine whether naftidrofuryl, when administered intravenously, is effective in alleviating symptoms and reducing progression of disease in patients with critical limb ischaemia.


METHODS
The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2012) and CENTRAL (2012, Issue 4). We searched the reference lists of articles. We also contacted pharmaceutical companies for any unpublished trials.


METHODS
All randomised controlled trials of critical limb ischaemia in which participants were randomly allocated to intravenous naftidrofuryl or control (either pharmacological, inert placebo or conservative therapy) were included. People with intermittent claudication were not included.


METHODS
Sixteen trials were identified, but eight were excluded because of poor methodology. The eight included trials involved a total of 269 participants from five different countries. The following outcomes were reported: pain reduction, rest pain/necrosis, progression of disease in terms of incidence of surgical reconstruction/amputation, mortality and side effects. On extraction of the data, odds ratios and mean differences were estimated where appropriate.


RESULTS
Treatment with naftidrofuryl tended to show reduction of pain evaluated by both analogue score and analgesic consumption, but the effect was statistically non-significant (mean difference (MD): 0.42; 95% confidence interval (CI)1.19 to 0.35). Similarly, improvement in rest pain or skin necrosis occurred, but these effects were also non-significant. The effect on mean ankle systolic pressure was inconclusive.


CONCLUSIONS
Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of people with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short, and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects.
Department of Public Health Sciences, The University of Edinburgh, Edinburgh, UK.
Felicity B
FB
Smith
Andrew
A
Bradbury
Gerry
G
Fowkes
D000671:Amputation, Surgical / Q000706:statistics & numerical data; D005121:Extremities / Q000098:blood supply*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D009257:Nafronyl / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009257:Nafronyl