Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis

Arch Intern Med. 1999 Feb 22;159(4):337-45. doi: 10.1001/archinte.159.4.337.


Background: There is no consensus on the efficacy of physical training, smoking cessation, and pharmacological therapy (pentoxifylline or nafronyl oxalate) in the treatment of patients with intermittent claudication at Fontaine stage II of disease.

Methods: A MEDLINE and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports, and trials without clinically meaningful outcomes were excluded. Included studies were graded level 1 (randomized and double- or assessor-blind), level 2 (open randomized), or level 3 (nonrandomized). Pain-free and total walking distance were the main outcomes considered; when feasible, end-of-treatment results were combined with appropriate meta-analytical procedures.

Results: In 5 level 2 studies, physical training increased pain-free and total walking distance significantly (139.0 m [95% confidence interval {CI}, 31.0 to 246.9 m] and 179.1 m [95% CI, 60.2 to 298.1 m], respectively). In a level 3 study, smoking cessation resulted in a nonsignificant increase in total walking distance of 46.7 m (95% CI, -19.3 to 112.7 m). In 6 level 1 studies, pentoxifylline increased both pain-free and total walking distance by 21.0 m (95% CI, 0.7 to 41.3 m) and 43.8 m (95% CI, 14.1 to 73.6 m), respectively. In 4 level 1 trials, nafronyl significantly increased pain-free walking distance (58.6 m [95% CI, 30.4 to 86.8 m]) and total walking distance (71.2 m [95% CI, 13.3 to 129.0 m]).

Conclusions: Physical training increased pain-free and total walking distance in level 2 studies. Only level 3 studies support the usefulness of smoking cessation. In level 1 studies, pentoxifylline and nafronyl increased pain-free and total walking distance, but the average effects were relatively small.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Exercise Therapy*
  • Humans
  • Intermittent Claudication / drug therapy
  • Intermittent Claudication / therapy*
  • Nafronyl / therapeutic use*
  • Pentoxifylline / therapeutic use*
  • Smoking Cessation*
  • Treatment Outcome
  • Vasodilator Agents / therapeutic use*


  • Vasodilator Agents
  • Nafronyl
  • Pentoxifylline