Skip navigation
Acute Pain | Chronic Pain | General

Smoking cessation and nafronyl for intermittent claudication

Clinical bottom line:

Nafronyl improves pain-free walking distance and total walking distance in patients with stage II intermittent claudication by approximately 60 metres and 70 metres respectively. However, it is not clear whether this improvement is of clinical relevance. No high quality data is available to assess the effects of smoking cessation. Studies have produced conflicting results, and there is therefore currently a lack of evidence for the effectiveness of this information.

Intermittent claudication - pain, tension and weakness on walking which intensifies until walking becomes impossible, but disappears on resting - is estimated to affect 2% of people over 65 years. It is most frequently caused by atherosclerotic narrowing of the iliac and femoral arteries, often in combination with similar lesions of more distal arteries of the leg.

Systematic review

Girolami B, Bernadi E, Prins MH, et al. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl. Arch Intern Med. 1999; 159:337-345.

Date review completed: December 1996

Number of trials included: 6 nafronyl / 4 smoking cessation

Number of patients: 629 / 866 smoking cessation

Control group: placebo / no intervention

Main outcomes: pain-free and total walking distance/time, ankle-brachial index, ankle pressure and peak blood flow.

Inclusion criteria were controlled trials of smoking cessation or nafronyl for intermittent claudication at stage II of the disease; randomised and non-randomised trials; trials not in selected population groups; placebo or inactive comparison; English language reports.

Reviewers pooled data from randomised trials only. This was calculated by combining the mean difference from each trial with 95% confidence interval. Descriptive summaries of studies and results were otherwise provided.


Smoking cessation

Four non-randomised cohort studies of 866 patients were included. These compared patients who stopped smoking with those who continued. It is difficult to interpret these findings owing to the lack of randomisation and therefore potential differences between groups. One small trial showed no difference on a number of measures. One trial showed that after 7 years 8.6% of smoking patients (26/304) had developed Fontaine stage III illness severity compared with none (0/39) of the stopped-smokers (95%CI 5.4% to 11.6%). A further trial of 415 patients failed to show any difference between groups. The fourth study did not provide extractable data.


Six randomised, double-blind trials compared nafronyl with placebo over three to six months. Doses ranged from 400 to 800 mg/day. Data for pain-free walking distance was available for four trials, three of which showed significant improvement. Pooled mean difference was 58.6 meters (95% CI, 30.4 to 86.8). There was also a significant improvement in total walking distance based on information from two trials (pooled mean difference 71.2 metres, 95% CI 13.3 to 129). There was no statistically significant effect on ankle-brachial index at rest (based on three trials).

Adverse effects

Reviewers did not consider adverse effects

This review also covered pentoxifylline and physical exercises for intermittent claudication. These are the subject of separate systematic reviews and are listed under related topics.

Further reading

Girolami B, Bernadi E, Prins MH et al. Antithrombotic drugs in the primary medical management of intermittent claudication: a meta-analysis. Thromb Haemost 1999; 81:715-22.

Related topics