Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Meta-analysis: Pentoxifylline improves walking in intermittent claudication

ACP J Club. 1997 Mar-Apr;126:37. doi:10.7326/ACPJC-1997-126-2-037


Source Citation

Hood SC, Moher D, Barber GG. Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. Can Med Assoc J. 1996 Oct 15; 155:1053-9.


Abstract

Objective

To evaluate the effectiveness of pentoxifylline in improving the walking capacity of patients with moderate intermittent claudication.

Data sources

Studies were identified using MEDLINE (1976 to 1994 inclusive) with the keywords pentoxifylline, peripheral vascular disease, and intermittent claudication. Reference lists of retrieved articles were also scanned, and content experts were contacted.

Study selection

Studies were included if they were randomized, double-blind, placebo-controlled trials; if they included patients who had moderate intermittent claudication caused by peripheral vascular disease at stage II or III according to Fontaine's classification; if the duration of the patients' intermittent claudication was > 3 months but < 5 years; if pentoxifylline was given at a dosage of 600 to 1800 mg/d for 2 to 26 weeks; and if the outcomes measured were pain-free walking distance (the distance walked on a treadmill before the onset of calf pain) and the absolute claudication distance (the maximum distance walked on a treadmill).

Data extraction

Data were extracted on the trial design, patient characteristics, dosages and treatment periods, and the means and standard deviations (SDs) for pain-free walking and absolute claudication distance.

Main results

Data on pain-free walking distance and on the absolute claudication distance were pooled and reported as weighted mean differences. 12 study groups in 11 trials were included in the analysis. Based on 11 study groups in 10 trials (612 patients), the overall weighted mean difference in pain-free walking distance was 29 meters (95% CI 13 to 46 m). Based on 7 study groups in 6 trials (511 patients), the overall weighted mean difference in absolute claudication distance was 48 m (CI 18 to 79 m). In a sensitivity analysis of pain-free walking distance, statistically significant treatment effects and no statistically significant heterogeneity were found when only trials of patients who had stage II disease and pain-free walking distance of 50 to 200 m were included (overall improvement in walking distance 23 m, CI 6 to 40 m). A similar analysis for absolute claudication distance showed that 2 conditions (medically eligible trials and shorter treatment duration) resulted in a statistically significant treatment effect and no significant heterogeneity.

Conclusion

Pentoxifylline therapy improves pain-free walking distance and absolute claudication distance in patients with moderate intermittent claudication.

Source of funding: No external funding.

For article reprint: Dr. D. Moher, Clinical Epidemiology Unit, Loeb Medical Research Institute, Ottawa Civic Hospital, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada. FAX 613-761-5351.


Commentary

Pentoxifylline has been widely used for the treatment of claudication for many years, but its effectiveness continues to be debated. This meta-analysis shows a statistically significant improvement in walking distance in patients with moderate claudication who were taking pentoxifylline.

The results, however, should be interpreted with caution. First, most trials that were included in the meta-analysis had < 20 patients in each treatment group; these small trials may provide an over-estimate of the treatment benefit because of publication bias. Second, the largest trial used intravenous rather than oral pentoxifylline. Finally, the beneficial effects of treatment may be more marked at the start of treatment (1).

The major issue for clinical application of the findings of Hood and colleagues is the relevance of the reported improvement in walking distance to the quality of life of the patient. The analysis shows an improvement of almost 50% in walking distance for patients in the control groups, with pentoxifylline providing an additional 30% improvement. In comparison, an increase in walking distance of about 400% has recently been shown after a supervised exercise program (2).

In view of these reservations, the case for routine use of pentoxifylline as a first-line treatment for moderate claudication is weak. A reasonable approach might be a trial of pentoxifylline in patients who, despite risk factor reduction and exercise (preferably in a supervised program), still have residual symptoms that are such that a small increase in walking distance would substantially improve their quality of life. Ultimately, this meta-analysis shows that a large study is required to address quality-of-life issues.

Jonathan Michaels, MChir
Northern General HospitalSheffield, England, UK

Jonathan Michaels, MChir
Northern General Hospital
Sheffield, England, UK


References

1. Ernst F, Kollar R, Resch KL. Does pentoxifylline prolong the walking distance in exercised claudicants? A placebo-controlled double-blind trial. Angiology. 1992; 43;121-5.

2. Perkins JM, Collin J, Creasy TS, Fletcher EW, Morris PJ. Exercise training versus angioplasty for stable claudication. Long and medium term results of a prospective, randomised trial. Eur J Vasc Endovasc Surg. 1996;11:409-13.