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Meta-Analysis
. 2012 Jul 11;2012(7):CD002070.
doi: 10.1002/14651858.CD002070.pub2.

Intravenous naftidrofuryl for critical limb ischaemia

Felicity B Smith  1 , Andrew Bradbury, Gerry Fowkes
Affiliations
Meta-Analysis

Intravenous naftidrofuryl for critical limb ischaemia

Felicity B Smith et al. Cochrane Database Syst Rev. .

Abstract

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.

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

Search 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 We also contacted pharmaceutical companies for any unpublished trials.

Selection criteria: 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.

Data collection and analysis: 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.

Main 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.

Authors' 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.

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Conflict of interest statement

Felicity Smith: Supplementary financial support was provided by Merck (Lipha Pharmaceuticals) for the original review. The review was conducted independently without input from Merck other than the provision of references and protocols. Subsequent updates were completed without financial support. Gerry Fowkes: None known Andrew Bradbury: None known

Figures

1.1
1.1. Analysis
Comparison 1 Naftidrofuryl versus control, Outcome 1 Pain evaluation by analogue scale.
1.2
1.2. Analysis
Comparison 1 Naftidrofuryl versus control, Outcome 2 Pain evaluation by analgesic consumption.
1.3
1.3. Analysis
Comparison 1 Naftidrofuryl versus control, Outcome 3 Mean ankle systolic pressure.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Bohme 1994 {published data only}
    1. Bohme H, Hartel U, Walter H. Naftidrofuryl versus alprostadil in stage III and IV of peripheral arterial occlusive disease. Medizinische Welt 1994;45(5):209‐13.
Heiss 1985 {published data only}
    1. Heiss HW, Peitgen A, Hasenfuss G, Just H. Treatment of arterial occlusive disease Stage IV with naftidrofuryl [Behandlung der arteriellen Verschlusskrankheit im Stadium IV mit Naftidrofuryl]. Berichtsband der 5. Jahrestagung der angiologischen Gesellschaften der BRD, Östereichs und der Schweiz (Report of the Berlin 1985 5th Joint Annual Meeting of the Angiological Associations of West Germany, Austria and Switzerland). Demeter, Gräfelfing, 1985:S335.
Horsch 1998 {published data only}
    1. Horsch S, Holscher U. Infusion therapy with ginkgo biloba special extract EGb 761 (TM) in patients with PAOD fontaine stages III and IV ‐ A reference‐controlled double‐blind clinical trial [Infusionstherapie mit Ginkgo‐biloba‐Spezialextrakt EGb 761 (TM) bei pAVK ‐ Eine referenzkontrollierte Doppelblindstudie an Patienten im Fontaine‐Stadium III und IV]. Munchener Medizinische Wochenschrift 1998;140(16):232‐6.
Karnik 1986 {published data only}
    1. Karnik R, Valentin A, Slany J. Prostacyclin versus naftidrofuryl: A randomised study in patients with peripheral arterial occlusive disease (PAOD) Stage III and IV [Prostacyclin versus Naftidrofuryl: Eine randomisierte Studie an Patienten mit peripherer arterieller Verschlußkrankheit (PAVK) Stadium III und IV]. Herz Kreislauf 1986;18(12):644‐7.
Meehan 1982a {published data only}
    1. Meehan SE, Preece PE, Walker WF. The usefulness of naftidrofuryl in severe peripheral ischaemia ‐ a symptomatic assessment using linear analogue scales. Angiology 1982;33(10):625‐34. - PubMed
Negus 1987 {published data only}
    1. Negus D, Irving JD, Friedgood A. Intra‐arterial prostacyclin compared to praxilene in the management of severe lower limb ischaemia: a double blind trial. Journal of Cardiovascular Surgery 1987;28(2):196‐9. - PubMed
Raftery 1982 {published data only}
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Testart 1994 {published data only}
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References to studies excluded from this review

Bianchi 1974 {published data only}
    1. Bianchi G. Double blind clinical experiences with L.S. 121 (praxilene) in patients with chronic ischemic peripheral syndromes [Esperienze cliniche in doppio cieco con L.S. 121 (praxilene) in pazienti portatori di sindromi ischemiche croniche periferiche]. Minerva Chirurgica 1974;29(15‐16):885‐90. - PubMed
Fellmann 1989 {published data only}
    1. Fellman N, Fabry R, Coudert J. Calf sweat lactate in peripheral arterial occlusive disease. American Journal of Physiology 1989;257(2 Pt 2):H395‐8. - PubMed
Greenhalgh 1981 {published data only}
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Horsch 1988 {published data only}
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Meehan 1982b {published data only}
    1. Meehan SE, Walker WF. Naftidrofuryl for severe ischaemia: assessment using skin pH micro‐electrode measurements. Current Medical Research & Opinion 1982;7(10):690‐9.
Mustapha 1984 {published data only}
    1. Mustapha NM, Jain SK, Dudley P, Redhead RG. The effect of oxygen inhalation and intravenous naftidrofuryl on the transcutaneous partial oxygen pressure in ischaemic lower limbs. Prosthetics & Orthotics International 1984;8(3):135‐8. - PubMed
Taggart 1989 {published data only}
    1. Taggart I, Wishart GC, Cuschieri RJ, MacBain GC. Effect of intravenous naftidrofuryl on transcutaneous oxygen pressure in severe peripheral vascular disease. Angiology 1989;40(10):895‐8. - PubMed
Wong 1980 {published data only}
    1. Wong AL, McBain GC. The importance of personality measurement in the assessment of response to treatment for ischaemic rest pain. British Journal of Surgery 1980;67(7):509‐13. - PubMed

Additional references

Jadad 1996
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Lehert 1990
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Leng 1993
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Peitgen 1985
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References to other published versions of this review

Smith 2000
    1. Smith FB, Bradbury A, Fowkes G. Intravenous naftidrofuryl for critical limb ischaemia. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD002070] - DOI - PubMed

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