0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review Article |

Treatment of Intermittent Claudication With Physical Training, Smoking Cessation, Pentoxifylline, or Nafronyl:  A Meta-analysis FREE

Bruno Girolami, MD; Enrico Bernardi, MD; Martin H. Prins, MD, PhD; Jan Wouter ten Cate, MD, PhD; Rohan Hettiarachchi, MD; Paolo Prandoni, MD, PhD; Antonio Girolami, MD; Harry R. Büller, MD, PhD
[+] Author Affiliations

From the Institute of Medical Semeiotics, University Hospital of Padua, Padua, Italy (Drs B. Girolami, Bernardi, Prandoni, and A. Girolami); and Department of Clinical Epidemiology and Biostatistics (Drs Prins and Hettiarachchi) and Center for Haemostasis, Thrombosis, Atherosclerosis, and Inflammation Research (Drs ten Cate and Büller), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.


Arch Intern Med. 1999;159(4):337-345. doi:10.1001/archinte.159.4.337.
Text Size: A A A
Published online

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.

Figures in this Article

INTERMITTENT claudication is most frequently caused by atherosclerotic narrowing of the iliac and femoral arteries, often in combination with similar lesions in at least 1 of the more distal arteries of the leg. It is the symptomatic expression of inability of the blood flow to supply the oxygen required by leg musculature during exercise.

Intermittent claudication (stage II of disease according to Fontaine et al1) and the underlying peripheral arterial obstructive disease is a common disorder that implies relevant treatment costs in Western societies.2,3 The prevalence is estimated to be around 5% in men older than 50 years,4,5 and the annual incidence increases from approximately 0.12% to 0.19% during middle age to 0.94% after the age of 65 years.6 Follow-up studies have shown that symptoms improve spontaneously in 40% of patients and progress in only 10% to 20%,7,8 leading to amputation in 7% within 5 years.7 Moreover, intermittent claudication is often associated with generalized atherosclerosis, which is responsible for a 2-fold increased death rate in these patients,5,7 largely from myocardial infarction and stroke, as compared with individuals without intermittent claudication.

Many treatment strategies (nonpharmacological, pharmacological, and revascularization procedures) have been proposed, aimed at eliminating the local atherosclerotic obstruction, slowing progression of the atherosclerotic disease, or simply ameliorating symptoms. The relative value of these treatment modalities is controversial. Conservative treatment of intermittent claudication includes physical training, smoking cessation, and drug therapy.

Physical training and smoking cessation are claimed to be the most effective conservative therapies for intermittent claudication, with the aim of increasing pain-free walking distance.9 A recent meta-analysis of mainly nonrandomized trials10 concluded that physical training should be applied as standard medical care but based this conclusion on pretraining and posttraining results, without a proper comparison group to account for the natural course of the disease. The mechanism that causes improvement with physical training is unclear. Potential explanations include improvement of collateral flow, redistribution of blood flow to ischemic areas, improvement of utilization and extraction of delivered oxygen from erythrocytes, positive influence on the blood viscosity, and raising of pain threshold.11,12

Smoking is a well-recognized risk factor for the development13,14 and progression1517 of lower-limb atherosclerosis. Discontinuation of smoking is claimed to reduce the risk of amputation.18 Although the pathophysiological mechanism is still unclear, the harmful consequences of smoking could be explained by its adverse effects on endothelium, platelets, and coagulation. Therefore, encouraging patients to quit smoking appears to be a logical step in the treatment of patients with intermittent claudication, although compliance with the advice to quit smoking permanently is generally low.

The vasoactive drugs pentoxifylline and nafronyl oxalate (naftidrofuryl) are commonly used in the pharmacological treatment of intermittent claudication in the Western world19; moreover, pentoxifylline is the only drug approved by the Food and Drug Administration for this indication. The rationale for the use of these agents is based on their ability to enhance red blood cell flexibility and to decrease blood viscosity (pentoxifylline), and to enhance aerobic glycolysis and oxygen consumption in ischemic tissues (nafronyl), although their exact mechanism of action is not well defined. However, the role of these vasoactive agents in the treatment of patients with arterial obstructive disease at stage II according to Fontaine et al1 is controversial.1922

Because of the uncertainty surrounding the effectiveness of these treatment strategies, we performed a meta-analysis to evaluate the evidence from controlled clinical trials.

We performed a MEDLINE computer-assisted search of the English-language medical literature (January 1976 to December 1996). A broad search frame was set with the use of the key words atherosclerosis, arteriosclerosis obliterans, peripheral vascular disease, and intermittent claudication. In addition, reference lists of retrieved articles and reviews on the subject were evaluated to identify additional and earlier articles. Studies were eligible for inclusion if they evaluated primary treatment of patients with intermittent claudication at stage II of disease1 with physical training, smoking cessation, pentoxifylline, or nafronyl, independent of their design. Studies conducted on selected populations (diabetic patients, hypertensive patients), reviews or meta-analysis of the literature, and case reports were not eligible. The quality of this selection process was evaluated on a random sample of 100 articles analyzed by 3 independent operators (B.G., E.B., and M.H.P.), achieving a κ value ranging from 0.90 to 0.95. Studies were excluded if they did not have a control group or compared 1 of the above-mentioned 4 strategies with another active treatment, were double reports or retrospective, or did not define or assess adequately any of the following outcomes: pain-free and total walking distance or time, ankle-brachial index before or after exercise, rest and peak blood flow, and ankle pressure. For the measurements of pain-free and total walking distance or time, the criterion was the use of a device that forced the patients to walk at a set speed.

Included trials were divided in 4 groups according to treatment type and graded by 2 independent observers (B.G. and E.B.) for the quality of their design in the following categories: level 1, randomized clinical trials, either double-blind or with specified blind assessment; level 2, other randomized trials; and level 3, nonrandomized controlled studies.

Level 3 studies were considered only if no data from level 1 studies were available. Data from included studies were extracted by 2 independent observers (B.G. and E.B.) by means of a standardized form. In case of disagreement, consensus was reached by adding a third observer (M.H.P.). Outcome data were then summarized in tabular format and, whenever possible and justifiable, combined by appropriate meta-analytical statistical procedures.23 The only criterion used for inclusion in the final summary measure of effectiveness was that the report enabled direct extraction of a difference in effect between the treatment groups and its common SD. Only results obtained at the end of the treatment period were compared, provided that baseline values for the outcomes considered were comparable among studies. Tests for homogeneity were performed, and no heterogeneity was detected. Results were expressed as common differences of the means with 95% confidence interval (CI).

PHYSICAL TRAINING

In total, 49 publications evaluating the efficacy of physical training were identified. Of these, 33 were without a control group,16,2455 1 compared physical training with another active intervention,56 3 were double reports,5759 and 1 was a retrospective study.60 None of the publications specified blind outcome assessment; hence, level 1 studies were not available. Therefore, 7 level 2 studies6167 and 4 level 3 studies6871 were analyzed. Among level 2 studies, 2 reported data on the same group of patients61,65; thus, 6 level 2 trials were available for analysis. Details of the study design are presented in Table 1.

Table Graphic Jump LocationTable 1. Overview of Clinical Trials on Physical Treatment or Smoking Cessation in Patients With Intermittent Claudication
Level 2 Trials

Sample size ranged from 14 to 50 patients in the 6 included trials. Patients randomized to active treatment underwent supervised exercise therapy (Table 1), except in 1 study,66 in which patients were advised to exercise at home without supervision. In 2 studies the effect of physical treatment was evaluated in patients undergoing a surgical intervention62 or receiving aspirin and dipyridamole.63 In 2 studies patients allocated to the control group received placebo tablets,64,66 while in the other 2 they were advised to continue with their usual lifestyle.65,67 Treatment duration ranged from 3 to 6 months, while follow-up varied from 3 to 12 months.

Pain-free walking was determined in 4 studies62,63,65,66 and total walking in 562,63,6567 of the 6 included trials (Table 2 and Figure 1). Although different experimental conditions (treadmill speed and slope), different units of measurement, and different concurrent treatments hampered summarizing calculations, pooled results of all trials yielded a statistically significant increase in pain-free and total walking distance at the end of treatment in favor of physical training compared with the control group (common difference of the means, 139.0 m [95% CI, 31.0 to 246.9 m] and 179.1 m [95% CI, 60.2 to 298.1 m], respectively). One study reported results on quality of life assessed by means of standard questionnaires; however, it was not possible to extract differences in effect between trained and control patients at the end of the treatment period.61

Table Graphic Jump LocationTable 2. Effect of Physical Treatment on Pain-Free and Total Walking Distances in Patients With Intermittent Claudication: Pooled Results at End of Treatment in Level 2 Studies*
Place holder to copy figure label and caption

Effect of physical training (level 2 studies) and pentoxifylline and nafronyl oxalate (level 1 studies) on pain-free walking distance in patients with peripheral arterial obstructive disease, Fontaine stage II. Means and 95% confidence intervals for each study and combined for each treatment are given.

Graphic Jump Location

There were no statistically significant effects on ankle-brachial index (at rest62,63,67 or after exercise63,67) or on calf blood flow (at rest63,64 or after exercise6264,66,67).

Level 3 Trials

In the 4 level 3 studies, sample size ranged from 13 to 42 patients.6871 Patients in the active treatment groups were given a supervised physical training program. Control patients received placebo tablets in 2 trials68,69 and were advised to continue with their usual lifestyle in 1 trial.70 In the other trial the treatment of control group patients was not specified.71 Treatment duration ranged from 2 to 6 months, while follow-up varied from 2 to 12 months. In general, the results of the level 3 trials were compatible with those of the level 2 trials (data not shown).

SMOKING CESSATION

In total, 7 publications dealing with the effect of smoking cessation on intermittent claudication were identified. Three were excluded; of these, 116 reported data on a subset of patients included in a subsequently published and larger trial,72 1 did not report clinically meaningful outcomes,74 and 1 was a retrospective study.60 Therefore, 4 level 3 studies were analyzed.13,15,72,73 Details of their design are presented in Table 1. Since none of the included studies reported similar outcomes, summary calculations were not feasible.

Sample size ranged from 52 to 415 patients. All included patients were smokers on referral13,15,72,73 or had stopped smoking within the past 6 months.72 Enrolled patients were strongly advised to discontinue smoking at recruitment; in total, 183 (24.2%) of 756 patients stopped smoking during the 10 months to 10 years of follow-up. In the first study, 41 current smokers were compared with 15 ex-smokers.15 The results were all not statistically significantly in favor of nonsmokers, yielding a difference in total walking distance of 46.7 m (95% CI, −19.3 to 112.7 m), a difference in resting ankle-brachial index of 0.04 (95% CI, −0.08 to 0.16), and differences in resting and postexercise ankle pressure of 11.7 mm Hg (95% CI, −4.5 to 27.9 mm Hg) and 3.7 mm Hg (95% CI, −28.7 to 36.1 mm Hg), respectively. Another study reported that, after 7 years of follow-up, 26 (8.6%) of 304 current smokers shifted from Fontaine stage II to III, vs none of the 39 patients who successfully quit smoking, for a difference of 8.6% (95% CI, 5.4% to 11.7%).72 This finding was not confirmed in a larger study73 in which no different incidence of critical limb ischemia and no deterioration in ankle-brachial index were observed between smokers and patients who quit smoking. However, in the same study, a larger number of failed revascularization procedures was observed among heavy smokers (P=.07). The fourth study did not provide raw data.13

PENTOXIFYLLINE

Of 28 eligible trials, 15 were excluded: 47578 reported data from a set of patients included in another report published later,79 3 did not have a control group,8082 and 8 compared pentoxifylline with another active treatment.8390 Therefore, 13 studies in which pentoxifylline was compared with placebo were analyzed; 12 were level 1 trials79,91101 and 1102 was a level 2 trial. In 1 study91 with a factorial design, 3 groups of patients were randomized to pentoxifylline, acenocoumarol, or placebo; these data were also considered for the placebo-controlled analysis. The details of the design of the included studies are summarized in Table 3.

Table Graphic Jump LocationTable 3. Overview of Clinical Trials on Pentoxifylline or Nafronyl in Patients With Intermittent Claudication*

Sample size ranged from 24 to 154 patients; treatment duration ranged from 1 to 12 months, and a placebo run-in phase varying from 1 to 12 weeks preceded active treatment in 7 studies. Pentoxifylline was mostly used in tablets, at a dosage ranging from 400 to 1200 mg/d. In 2 trials, the active treatment was administered intravenously, in the first101 at a mean dose of 600 mg/d during 2 weeks and in the second102 at a mean dose of 400 mg/d during 4 weeks. One report included patients belonging to Fontaine stages II to IV.100 However, stage II patients were allocated to an independent group, and the results were reported separately. Therefore, this part of the study was analyzed.

Pain-free walking distance was evaluated in 9 level 1 trials and in 1 level 2 trial. Three level 1 trials did not provide data in an appropriate format to be included in the final summary table.91,97,100 The pooled results of the other 6 studies are illustrated in Table 4 and Figure 1, showing a statistically significant effect of pentoxifylline on pain-free walking distance (common difference of the means, 21.0 m [95% CI, 0.7 to 41.3 m]), as compared with placebo.79,9295,101

Table Graphic Jump LocationTable 4. Effect of Pentoxifylline vs Placebo on Pain-Free and Total Walking Distances and Ankle-Brachial Index: Pooled Results at the End of Treatment in Level 1 Studies*

Total walking distance was evaluated in 8 level 1 and in 1 level 2 trials. One level 1 trial97 and the level 2 trial102 did not provide data in an appropriate format to be summarized. Table 4 depicts the pooled results of 7 level 1 studies yielding a statistically significantly beneficial effect of pentoxifylline over placebo (common difference of the means, 43.8 m [95% CI, 14.1 to 73.6 m]).79,92,93,96,98,99,101

There were no statistically significant effects on ankle-brachial index at rest91,94,97,101 or after exercise91,94,97(Table 4). Resting calf blood flow was evaluated in 1 level 1 trial97 and a slight but statistically significant reduction of blood flow was measured in patients treated with pentoxifylline as compared with placebo (−0.4 mL/min per 100 mL [95% CI, −1.2 to 0.37 mL/min per 100 mL). Calf blood pressure was reported by 1 study, and no significant differences were observed among treated and control patients.98

NAFRONYL

Of 11 eligible trials, 5 were excluded: 2 did not report any of the outcomes of interest103,104 and 3 compared nafronyl with another active treatment.26,37,105 Therefore, 6 trials were analyzed. All of these were level 1 studies (Table 3).106111 Sample size ranged from 40 to 180 patients. The study duration ranged from 3 to 6 months, and a placebo run-in phase varying from 2 to 4 weeks preceded the active treatment administration in 5 trials. Nafronyl was only administered orally, with a dosage ranging from 400 to 800 mg/d.

Pain-free walking distance was evaluated in 6 trials. The pooled results of 4 studies are illustrated in Table 5 and Figure 1, showing a statistically significant effect of nafronyl (common difference of the means, 58.6 m [95% CI, 30.4 to 86.8 m]), as compared with placebo.107109,111 Of the other 2 trials, the data could not be summarized.106,110

Table Graphic Jump LocationTable 5. Effect of Nafronyl vs Placebo on Pain-Free and Total Walking Distances and Ankle-Brachial Index: Pooled Results at the End of Treatment in Level 1 Studies*

Total walking distance was evaluated in 4 trials. The results of 2 of these trials could be summarized (Table 5), yielding a statistically significant advantage of nafronyl over placebo (common difference of the means, 71.2 m [95% CI, 13.3 to 129.0 m]).108,109 The results of the other 2 trials were not in an appropriate format to be summarized.106,110

There were no statistically significant effects on ankle-brachial index at rest (Table 5).107,109,110

Intermittent claudication is a disease affecting approximately 5% of elderly men in Western societies, and debate is ongoing about the efficacy of the various generally recommended treatment strategies. Physical exercise and smoking cessation are usually regarded as the first step in the treatment of this condition. The results of our meta-analysis of randomized controlled trials indicate that the initiation of physical exercise in patients at stage II of disease1 is associated with an increase in pain-free walking distance of approximately 140 m at the end of treatment and a similar increase (180 m) in total walking distance. However, these results were obtained in only 94 and 112 patients, respectively, and the effect is likely to be overestimated. There appears to be a large potential for factors such as group incomparability and publication bias to have influenced these results.

The schedule of prescribed exercise and associated results varied among individual studies. In 1 randomized study with a small patient population, a nonsupervised exercise program determined a significant effect on pain-free walking distance as well as on total walking distance after 6 months,66 while in another randomized study that included more patients and with a supervised exercise program, the effect was nonsignificant (Table 2).62 Recently, in 2 small trials, patients with intermittent claudication were randomized to supervised vs home-based physical training; preliminary results seem to show an advantage in favor of patients treated in a supervised setting.112,113 However, no definite comparison is yet available, and prescribing expensive supervised exercise programs to these patients remains controversial.

Data supporting the usefulness of smoking cessation are derived only from cohort studies. They do suggest a potential benefit, but since it is conceivable that successful smoking cessation is associated with other lifestyle changes, the favorable result could result from these confounding factors. Formal meta-analysis was not possible.

The effectiveness of pentoxifylline and nafronyl with regard to an increase in pain-free and total walking distance is well documented. By means of sensitivity analysis, it can be demonstrated that a study of 40 patients in the case of pentoxifylline and more than 1200 patients in the case of nafronyl with a true zero effect (assuming comparable SDs) would be needed to make the results not statistically significant. Based on our results, the average increase in pain-free walking distance is limited to 20 to 60 m. Moreover, studies that assess the effect of these drugs on degree of disability and quality of life experienced by this group of patients are not available. Hence, although the effectiveness of these 2 agents is convincingly demonstrated, especially for nafronyl, it is questionable whether their prescription to patients with intermittent claudication at stage II of disease would be also clinically relevant. In current clinical practice, the administration of these drugs should therefore be evaluated on a patient-by-patient basis. One earlier and preliminary publication showed similar results and conclusions.114 Other authors obtained similar results with regard to the effect pentoxifylline on walking distance.115

We believe our results are generalizable to patients with intermittent claudication who have stage II disease. Although we limited the data search to English-language literature only, the potential for error because of a language bias is extremely low and, if present, is trivial ("Tower of Babel error").116

We conclude that physical training is a potentially effective treatment modality, as is smoking cessation. However, available evidence derived from intervention studies in favor of these nonpharmacological treatment strategies is weak (small samples in level 2 and level 3 studies, respectively). Thus, it is unclear whether prescribing supervised physical training programs to patients with obstructive arterial disease is cost-effective, since this intervention modality is expensive and time-consuming. Data from larger properly designed clinical trials, assessing also the degree of disability and quality of life,61,112,113 are strongly warranted. For now, advising patients to walk and stop smoking is likely to be all that is required. Pentoxifylline and nafronyl are widely used in Western societies, and the results of our analysis confirm their effectiveness in improving walking distance; however, the clinical relevance of such a small effect should be elucidated by properly designed trials that also assess also degree of disability and quality of life.

Accepted for publication May 26, 1998.

Corresponding author: Bruno Girolami, MD, Istituto di Semeiotica Medica, Universitá di Padova, Via Ospedale 105, 35100 Padova, Italy (e-mail: girolami@ux1.unipd.it).

Fontaine  VRKim  MKicny  R Die chirurgische Behandlung der peripheren Durchblutungsstörungen. Helv Chir Acta. 1954;5/6499- 533
Drummond  MDavies  L Economic evaluation of drugs in peripheral vascular disease and stroke. J Cardiovasc Pharmacol. 1994;23(suppl 3)4S- 7S
Link to Article
Rudofsky  Gvan Laak  HH Treatment costs of peripheral arterial occlusive disease in Germany: a comparison of costs and efficacy. J Cardiovasc Pharmacol. 1994;23(suppl 3)22S- 25S
Link to Article
Dormandy  JMahir  MAcsády  G  et al.  Fate of the patient with chronic leg ischaemia. J Cardiovasc Surg (Torino). 1989;3050- 57
Balkau  BVray  MEschwege  E Epidemiology of peripheral arterial disease. J Cardiovasc Pharmacol. 1994;23(suppl 3)8S- 16S
Link to Article
Kannel  WBSkinner  JJSchwartz  MJShurtleff  D Intermittent claudication: incidence in the Framingham Study. Circulation. 1970;41875- 883
Link to Article
Verstraete  M Current therapy for intermittent claudication. Drugs. 1982;24240- 247
Link to Article
Lowe  GDO Drugs in cerebral and peripheral arterial disease. BMJ. 1990;300524- 528
Link to Article
Spitzer  SBach  RSchieffer  H Walk training and drug treatment in patients with peripheral arterial occlusive disease stage II: a review. Int Angiol. 1992;11204- 210
Gardner  AWPoehlman  ET Exercise rehabilitation programs for the treatment of claudication pain: a meta-analysis. JAMA. 1995;274975- 980
Link to Article
Ernst  E Peripheral vascular disease: benefits of exercise. Sports Med. 1991;12149- 151
Link to Article
Tsang  GMKGreen  MACrow  AJ  et al.  Chronic muscle stimulation improves ischaemic muscle performance in patients with peripheral vascular disease. Eur J Vasc Surg. 1994;8419- 422
Link to Article
Hughson  WGMann  JITibbs  DJWoods  HFWalton  I Intermittent claudication: factors determining outcome. BMJ. 1978;11377- 1379
Link to Article
Hughson  WGMann  JIGarrod  A Intermittent claudication: prevalence and risk factors. BMJ. 1978;11379- 1381
Link to Article
Quick  CRGCotton  LT The measured effect of stopping smoking on intermittent claudication. Br J Surg. 1982;69(suppl)S24- S26
Link to Article
Jonason  TRingqvist  I Factors of prognostic importance for subsequent rest pain in patients with intermittent claudication. Acta Med Scand. 1985;21827- 33
Link to Article
Kannel  WBShurtleff  D The Framingham Study: cigarettes and the development of intermittent claudication. Geriatrics. 1973;2861- 68
Juergens  JBarker  NHines  E Atherosclerosis obliterans: review of 520 cases with special reference to pathogenic and prognostic factors. Circulation. 1960;21188- 195
Link to Article
Bevan  EGWaller  PCRamsay  LE Pharmacological approaches to the treatment of intermittent claudication. Drugs Aging. 1992;2125- 136
Link to Article
Cameron  HAWaller  PCRamsay  LE Drug treatment of intermittent claudication: a critical analysis of the methods and findings of published clinical trials, 1965-1985. Br J Clin Pharmacol. 1988;26569- 576
Link to Article
Kriessmann  A Peripheral arterial occlusive disease: conservative treatment of intermittent claudication. J Cardiovasc Pharmacol. 1990;16(suppl 3)S72- S74
Link to Article
Radack  KWydersky  RJ Conservative management of intermittent claudication. Ann Intern Med. 1990;113135- 146
Link to Article
Rao  CR Linear Statistical Inference and Its Applications.  New York, NY John Wiley & Sons Inc1973;389- 391
Ekroth  RDahllöf  AGGundevall  BHolm  JSchersten  T Physical training of patients with intermittent claudication: indications, methods, and results. Surgery. 1978;84640- 643
Sorlie  DMyhre  K Effects of physical training in intermittent claudication. Scand J Clin Lab Invest. 1978;38217- 222
Link to Article
Kiesewetter  HJung  FBlume  JBulling  BGerhards  M Conservative drug therapy and walking exercise in stage IIb peripheral arterial occlusion disease. Klin Wochenschr. 1986;641061- 1069
Carter  SAHamel  ERPaterson  JMSnow  CJMymin  D Walking ability and ankle systolic pressures: observations in patients with intermittent claudication in a short-term walking exercise program. J Vasc Surg. 1989;10642- 649
Link to Article
Andriessen  MPBarendsen  GJWouda  AAde Pater  L The effect of six months intensive physical training on the circulation in the legs of patients with intermittent claudication. Vasa. 1989;1856- 62
Williams  LREkers  MACollins  PSLee  JF Vascular rehabilitation: benefits of a structured exercise/risk modification program. J Vasc Surg. 1991;14320- 326
Link to Article
Lepantalo  MSundberg  SGordin  A The effects of physical training and flunarizine on walking capacity in intermittent claudication. Scand J Rehabil Med. 1984;16159- 162
Jonason  TJonzon  BRingqvist  IÖman-Rydberg  A Effect of physical training on different categories of patients with intermittent claudication. Acta Med Scand. 1979;206253- 258
Link to Article
Clifford  PCDavies  PWHayne  JABaird  RN Intermittent claudication: is a supervised exercise class worth while? BMJ. 1980;2801503- 1505
Link to Article
Jonason  TRingqvist  I Effect of training on the post-exercise ankle blood pressure reaction in patients with intermittent claudication. Clin Physiol. 1987;763- 69
Link to Article
Hiatt  WRNawaz  DRegensteiner  JGHossack  KF The evaluation of exercise performance in patients with peripheral vascular disease. J Cardiopulm Rehabil. 1988;12525- 532
Link to Article
Ruell  PAImperial  ESBonar  FJThursby  PFGass  GC The effect of physical training on walking tolerance and venous lactate concentration. Eur J Appl Physiol. 1984;52420- 425
Link to Article
Boyd  CEBird  PJTeates  CDWellons  HAMacDougall  MAWolfe  LA Pain free physical training in intermittent claudication. J Sports Med. 1984;24112- 122
Diehm  CKuhn  AStrauss  RMuller  CHKubler  W Effects of regular physical training in a supervised class and additional intravenous prostaglandin E1 and naftidrofuryl infusion therapy in patients with intermittent claudication: a controlled study. Vasa. 1989;28(suppl)26- 30
Andriessen  MPHMBarendsen  GJWouda  AADe Pater  L Changes of walking distance in patients with intermittent claudication during six months intensive physical training. Vasa. 1989;1863- 68
Holm  JSchersten  T Exercise training of patients with intermittent claudication. Scand J Rehabil Med. 1983;9(suppl)20- 26
Alpert  JSLarsen  OELassen  NA Exercise and intermittent claudication: blood flow in the calf muscle during walking studied by xenon-133 clearance method. Circulation. 1969;39353- 359
Link to Article
Wisham  LHAbramson  ASEbel  A Value of exercise in peripheral arterial disease. JAMA. 1953;510- 12
Link to Article
Jonason  TRingqvist  I Prediction of the effect of training on the walking tolerance in patients with intermittent claudication. Scand J Rehabil Med. 1987;1947- 50
Feinberg  RLGregory  RTWheeler  JR  et al.  The ischemic window: a method for the objective quantitation of the training effect in exercise therapy for intermittent claudication. J Vasc Surg. 1992;16244- 250
Link to Article
McAllister  FF The fate of patients with intermittent claudication managed nonoperatively. Am J Surg. 1976;132593- 595
Link to Article
Myhre  KSorlie  DG Physical activity and peripheral atherosclerosis. Scand J Soc Med Suppl. 1982;29195- 201
Rosetzsky  AStruckmann  JMathiesen  FR Minimal walking distance following exercise treatment in patients with arterial occlusive disease. Ann Chir Gynaecol. 1985;74261- 264
Pancera  PPrior  MZannoni  MLucchese  LDe Marchi  SArosio  E Micro- and macrocirculatory, and biohumoral changes after a month of physical exercise in patients with intermittent claudication. Scand J Rehabil Med. 1995;2773- 76
Skinner  JSStrandness  DE  Jr Exercise and intermittent claudication: effect of physical training. Circulation. 1967;3623- 29
Link to Article
Hall  JABarnard  RJ The effects of an intensive 26-day program of diet and exercise on patients with peripheral vascular disease. J Cardiac Rehabil. 1982;2569- 574
Pritikin  NKern  JKaye  SM Diet and exercise as a total therapeutic regimen for the rehabilitation of patients with severe peripheral vascular disease. Arch Phys Med Rehabil. 1975;56558
Zetterqvist  S The effect of active training on the nutritive blood flow in exercising ischemic legs. Scand J Clin Lab Invest. 1970;25101- 111
Link to Article
Skinner  JSStrandness  DE Exercise and intermittent claudication: effect of repetition and intensity of exercise. Circulation. 1967;3615- 22
Link to Article
Blumchen  GLandry  FKiefer  HSchlosser  V Hemodynamic response of claudicating extremities: evaluation of a long range exercise program. Cardiology. 1970;55114- 127
Link to Article
Jonason  TRingqvist  IÖman-Rydberg  A Home-training of patients with intermittent claudication. Scand J Rehabil Med. 1981;13137- 141
Johnson  ECVoyles  WFAtterbom  HAPathak  DSutton  MFGreene  ER Effects of exercise training on common femoral artery blood flow in patients with intermittent claudication. Circulation. 1989;80(suppl III)III-59- III-72
Link to Article
Perkins  JMTCollin  JCreasy  TSFletcher  EWLMorris  PJ Exercise training versus angioplasty for stable claudication: long and medium term results of a prospective, randomised trial. Eur J Vasc Endovasc Surg. 1996;11409- 413
Link to Article
Lundgren  FDahllöf  AGSchersten  TBylund-Fellenius  AC Muscle enzyme adaption in patients with peripheral arterial insufficiency: spontaneous adaption, effect of different treatments and consequences on walking performance. Clin Sci. 1989;77485- 493
Holm  JDahllöf  AGBjorntorp  PSchersten  T Enzyme studies in muscles of patients with intermittent claudication: effect of training. Scand J Clin Lab Invest. 1973;128(suppl)201- 205
Larsen  OALassen  NA Effect of daily muscular exercise in patients with intermittent claudication. Scand J Clin Lab Invest 1966;99(suppl)168- 171
Cronenwett  JLWarner  KGZelenock  GB  et al.  Intermittent claudication: current results of nonoperative management. Arch Surg. 1984;119430- 436
Link to Article
Regensteiner  JGSteiner  JFHiatt  WR Exercise improves functional status in patients with peripheral arterial disease. J Vasc Surg. 1996;23104- 115
Link to Article
Lundgren  FDahllöf  AGLundholm  KSchersten  TVolkmann  R Intermittent claudication: surgical reconstruction or physical training? a prospective randomized trial of treatment efficiency. Ann Surg. 1989;209346- 355
Link to Article
Mannarino  EPasqualini  LInnocente  SScricciolo  VRignanese  ACiuffetti  G Physical training and antiplatelet treatment in stage II peripheral arterial occlusive disease: alone or combined? Angiology. 1991;42513- 521
Link to Article
Dahllöf  AGBjorntorp  PHolm  JSchersten  T Metabolic activity of skeletal muscle in patients with peripheral arterial insufficiency: effect of physical training. Eur J Clin Invest. 1974;49- 15
Link to Article
Hiatt  WRWolfel  EEMeier  RHRegensteiner  JG Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Circulation. 1994;901866- 1874
Link to Article
Larsen  OALassen  NA Effect of daily muscular exercise in patients with intermittent claudication. Lancet. 1966;21093- 1096
Link to Article
Hiatt  WRRegensteiner  JGHargarten  MEWolfel  EEBrass  EP Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation. 1990;81602- 609
Link to Article
Dahllöf  AGHolm  JSchersten  TSivertsson  R Peripheral arterial insufficiency: effect of physical training on walking tolerance, calf blood flow, and blood flow resistance. Scand J Rehabil Med. 1976;819- 26
Mannarino  EPasqualini  LMenna  MMaragoni  GOrlandi  U Effects of physical training on peripheral vascular disease: a controlled study. Angiology. 1989;405- 10
Link to Article
Ernst  EEWMatrai  A Intermittent claudication, exercise, and blood rheology. Circulation. 1987;761110- 1114
Link to Article
Ericsson  BHaeger  KLindell  SE Effect of physical training on intermittent claudication. Angiology. 1970;21188- 192
Link to Article
Jonason  TBergstrom  R Cessation of smoking in patients with intermittent claudication. Acta Med Scand. 1987;221253- 260
Link to Article
Smith  IFranks  PJGreenhalgh  RMPoulter  NRPowell  JT The influence of smoking cessation and hypertriglyceridaemia on the progression of peripheral arterial disease and the onset of critical ischaemia. Eur J Vasc Endovasc Surg. 1996;11402- 408
Link to Article
Vasli  LRFoss  OP Serum thiocyanate, smoking habits and smoking cessation trial in patients with peripheral atherosclerosis. Scand J Clin Lab Invest. 1987;47399- 403
Link to Article
Porter  JMBaur  GM Pharmacologic treatment of intermittent claudication. Surgery. 1982;92966- 971
Reich  TGillings  D Effects of pentoxifylline on severe intermittent claudication. Angiology. 1987;38651- 656
Link to Article
Reich  TCutler  BCLee  BY  et al.  Pentoxifylline in the treatment of intermittent claudication of the lower limbs. Angiology. 1984;35389- 395
Link to Article
Porter  JMCutler  BSLee  BY  et al.  Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. Am Heart J. 1982;10466- 72
Link to Article
Gillings  DKoch  GReich  TStager  WJ Another look at the pentoxifylline efficacy data for intermittent claudication. J Clin Pharmacol. 1987;27601- 609
Link to Article
Roeren  TLeVeen  RFNugent  L Photoplethysmographic documentation of improved microcirculation after pentoxifylline therapy. Angiology. 1988;39929- 933
Link to Article
AbuRahma  AFWoodruff  BA Effects and limitations of pentoxifylline therapy in various stages of peripheral vascular disease of the lower extremity. Am J Surg. 1990;160266- 270
Link to Article
Poggesi  LScarti  LBoddi  MMasotti  GSerneri  GG Pentoxifylline treatment in patients with occlusive peripheral arterial disease: circulatory changes and effects on prostaglandin synthesis. Angiology. 1985;36628- 637
Link to Article
Pignoli  PCiccolo  FVilla  VLongo  T Comparative evaluation of buflomedil and pentoxiphylline in patients with peripheral arterial occlusive disease. Curr Ther Res. 1985;37596- 606
Chacon-Quevedo  AEguaras  MGCalleja  F  et al.  Comparative evaluation of pentoxifylline, buflomedil, and nifedipine in the treatment of intermittent claudication of the lower limbs. Angiology. 1994;45647- 653
Link to Article
Perhoniemi  VSalmenkivi  KSundberg  SJohnsson  RGordin  A Effects of flunarizine and pentoxifylline on walking distance and blood rheology in claudication. Angiology. 1984;35366- 372
Link to Article
Feine-Haake  G Assessment of the therapeutic efficacy of pentoxifylline (Trental): a double-blind trial in geriatric patients with vascular disorder. Pharmatherapeutica. 1983;3(suppl 1)46- 51
Accetto  B Beneficial hemorheologic therapy of chronic peripheral arterial disorders with pentoxifylline: results of a double-blind study versus vasodilator-nylidrin. Am Heart J. 1982;103864- 869
Link to Article
Trübestein  GTrübestein  RDuong  QD Comparative evaluation of the effectiveness of buflomedil and pentoxiphylline in patients with arterial occlusive disease. Angiology. 1981;32705- 709
Link to Article
Mashiah  APatel  PSchraibman  IGCharlesworth  D Drug therapy in intermittent claudication: an objective assessment of the effects of three drugs in patients with intermittent claudication. Br J Surg. 1978;65342- 345
Link to Article
Deutschinoff  AGrozdinsky  L Rheological and anticoagulant therapy of patients with chronic peripheral occlusive arterial disease (COAD). Angiology. 1987;38351- 358
Link to Article
Dettori  AGPini  MMoratti  A  et al.  Acenocoumarol and pentoxifylline in intermittent claudication: a controlled clinical study. Angiology. 1989;40237- 248
Link to Article
Ernst  EKollar  LResch  KL Does pentoxifylline prolong the walking distance in exercised claudicants? a placebo-controlled double-blind trial. Angiology. 1992;43121- 125
Link to Article
Lindgärde  FJelnes  RBjorkman  H  et al.  Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Circulation. 1989;801549- 1556
Link to Article
Donaldson  DRHall  TJKester  RCRamsden  CWWiggins  PA Does oxpentifylline (Trental) have a place in the treatment of intermittent claudication? Curr Med Res Opin. 1984;935- 40
Link to Article
Di Perri  TGuerrini  M Placebo controlled double blind study with pentoxifylline of walking performance in patients with intermittent claudication. Angiology. 1983;3440- 45
Link to Article
Reilly  DTQuinton  DNBarrie  WW A controlled trial of pentoxifylline (Trental 400) in intermittent claudication: clinical, haemostatic and rheological effects. N Z Med J. 1987;100445- 447
Gallus  ASGleadow  FDupont  P  et al.  Intermittent claudication: a double-blind crossover trial of pentoxifylline. Aust N Z J Med. 1985;15402- 409
Link to Article
Bollinger  AFrei  CH Double-blind trial of pentoxifylline against placebo in patients with intermittent claudication. Pharmatherapeutica. 1977;1557- 561
Volker  D Treatment of artheriopathies with pentoxifylline (Trental 400): results of a double-blind study. Pharmatherapeutica. 1983;3(suppl 1)136- 142
Tonak  JKnecht  HGroitl  H Treatment of circulatory disturbances with pentoxifylline: double-blind study with Trental. Pharmatherapeutica. 1983;3(suppl 1)126- 135
Rudofsky  GHaussler  KFKünkel  HP  et al.  Intravenous treatment of chronic peripheral occlusive arterial disease: a double-blind, placebo-controlled, randomized, multicenter trial of pentoxifylline. Angiology. 1989;40639- 649
Link to Article
Scheffler  Pde la Hamette  DGross  JMueller  HSchieffer  H Intensive vascular training in stage IIb in peripheral arterial occlusive disease: the additive effects of intravenous prostaglandin E1 or intravenous pentoxifylline during training. Circulation. 1994;90818- 822
Link to Article
Waters  KJCraxford  ADChamberlain  J The effect of naftidrofuryl (Praxilene) on intermittent claudication. Br J Surg. 1980;67349- 351
Link to Article
Ruckley  CVCallam  MJFerrington  CMPrescott  RJ Naftidrofuryl for intermittent claudication: a double-blind controlled trial. BMJ. 1978;1620
Rosas  GCerdeyra  CLucas  MAParano  JRVilla  JJ Comparison of safety and efficacy of buflomedil and naftidrofuryl in the treatment of intermittent claudication. Angiology. 1981;32291- 297
Link to Article
Karnik  RValentin  AStöllberger  CSlany  J Effects of naftidrofuryl in patients with intermittent claudication. Angiology. 1988;39234- 240
Link to Article
Adhoute  GBacourt  FBarral  M  et al.  Naftidrofuryl in chronic arterial disease: results of a six month controlled multicenter study using naftidrofuryl tablets 200 mg. Angiology. 1986;37160- 167
Link to Article
Trübestein  GBöhme  HHeidrich  H  et al.  Naftidrofuryl in chronic arterial occlusive disease: results of a controlled multicenter study. Angiology. 1984;35701- 708
Link to Article
Adhoute  GAndreassian  HBoccalon  M  et al.  Treatment of stage II chronic arterial disease of the lower limbs with the serotoninergic antagonist naftidrofuryl: results after six months of a controlled multicenter study. J Cardiovasc Pharmacol. 1990;16(suppl 3)S75- S80
Link to Article
Moody  APAl-Khaffaf  HSLehert  PHarris  PLCharlesworth  D An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl. J Cardiovasc Pharmacol. 1994;23(suppl 3)S44- S47
Link to Article
Clyne  CACGalland  RBFox  MJGustave  RJantet  GHJamieson  CW A controlled trial of naftidrofuryl (Praxilene) in the treatment of intermittent claudication. Br J Surg. 1980;67347- 348
Link to Article
Patterson  RBPinto  BMarcus  BColucci  ABraun  TRoberts  M Value of a supervised exercise program for the therapy of arterial claudication. J Vasc Surg. 1997;25312- 319
Link to Article
Regensteiner  JGMeyer  TJKrupski  WCCranford  LSHiatt  WR Hospital- vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease. Angiology. 1997;48291- 300
Link to Article
Girolami  BBernardi  EKoelemay  MPrandoni  PGirolami  APrins  MH Pharmacological treatment of peripheral arterial occlusive disease (Fontaine's stage II): a meta-analysis of randomised clinical trials [abstract]. Thromb Haemost. 1995;61386
Hood  SCMoher  DBarber  GG Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. CMAJ. 1996;1551053- 1059
Grégorie  GDerderian  FLe Lorier  J Selecting the language of the publications included in a meta-analysis: is there a Tower of Babel bias? J Clin Epidemiol. 1995;48159- 163
Link to Article

Figures

Place holder to copy figure label and caption

Effect of physical training (level 2 studies) and pentoxifylline and nafronyl oxalate (level 1 studies) on pain-free walking distance in patients with peripheral arterial obstructive disease, Fontaine stage II. Means and 95% confidence intervals for each study and combined for each treatment are given.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Overview of Clinical Trials on Physical Treatment or Smoking Cessation in Patients With Intermittent Claudication
Table Graphic Jump LocationTable 2. Effect of Physical Treatment on Pain-Free and Total Walking Distances in Patients With Intermittent Claudication: Pooled Results at End of Treatment in Level 2 Studies*
Table Graphic Jump LocationTable 3. Overview of Clinical Trials on Pentoxifylline or Nafronyl in Patients With Intermittent Claudication*
Table Graphic Jump LocationTable 4. Effect of Pentoxifylline vs Placebo on Pain-Free and Total Walking Distances and Ankle-Brachial Index: Pooled Results at the End of Treatment in Level 1 Studies*
Table Graphic Jump LocationTable 5. Effect of Nafronyl vs Placebo on Pain-Free and Total Walking Distances and Ankle-Brachial Index: Pooled Results at the End of Treatment in Level 1 Studies*

References

Fontaine  VRKim  MKicny  R Die chirurgische Behandlung der peripheren Durchblutungsstörungen. Helv Chir Acta. 1954;5/6499- 533
Drummond  MDavies  L Economic evaluation of drugs in peripheral vascular disease and stroke. J Cardiovasc Pharmacol. 1994;23(suppl 3)4S- 7S
Link to Article
Rudofsky  Gvan Laak  HH Treatment costs of peripheral arterial occlusive disease in Germany: a comparison of costs and efficacy. J Cardiovasc Pharmacol. 1994;23(suppl 3)22S- 25S
Link to Article
Dormandy  JMahir  MAcsády  G  et al.  Fate of the patient with chronic leg ischaemia. J Cardiovasc Surg (Torino). 1989;3050- 57
Balkau  BVray  MEschwege  E Epidemiology of peripheral arterial disease. J Cardiovasc Pharmacol. 1994;23(suppl 3)8S- 16S
Link to Article
Kannel  WBSkinner  JJSchwartz  MJShurtleff  D Intermittent claudication: incidence in the Framingham Study. Circulation. 1970;41875- 883
Link to Article
Verstraete  M Current therapy for intermittent claudication. Drugs. 1982;24240- 247
Link to Article
Lowe  GDO Drugs in cerebral and peripheral arterial disease. BMJ. 1990;300524- 528
Link to Article
Spitzer  SBach  RSchieffer  H Walk training and drug treatment in patients with peripheral arterial occlusive disease stage II: a review. Int Angiol. 1992;11204- 210
Gardner  AWPoehlman  ET Exercise rehabilitation programs for the treatment of claudication pain: a meta-analysis. JAMA. 1995;274975- 980
Link to Article
Ernst  E Peripheral vascular disease: benefits of exercise. Sports Med. 1991;12149- 151
Link to Article
Tsang  GMKGreen  MACrow  AJ  et al.  Chronic muscle stimulation improves ischaemic muscle performance in patients with peripheral vascular disease. Eur J Vasc Surg. 1994;8419- 422
Link to Article
Hughson  WGMann  JITibbs  DJWoods  HFWalton  I Intermittent claudication: factors determining outcome. BMJ. 1978;11377- 1379
Link to Article
Hughson  WGMann  JIGarrod  A Intermittent claudication: prevalence and risk factors. BMJ. 1978;11379- 1381
Link to Article
Quick  CRGCotton  LT The measured effect of stopping smoking on intermittent claudication. Br J Surg. 1982;69(suppl)S24- S26
Link to Article
Jonason  TRingqvist  I Factors of prognostic importance for subsequent rest pain in patients with intermittent claudication. Acta Med Scand. 1985;21827- 33
Link to Article
Kannel  WBShurtleff  D The Framingham Study: cigarettes and the development of intermittent claudication. Geriatrics. 1973;2861- 68
Juergens  JBarker  NHines  E Atherosclerosis obliterans: review of 520 cases with special reference to pathogenic and prognostic factors. Circulation. 1960;21188- 195
Link to Article
Bevan  EGWaller  PCRamsay  LE Pharmacological approaches to the treatment of intermittent claudication. Drugs Aging. 1992;2125- 136
Link to Article
Cameron  HAWaller  PCRamsay  LE Drug treatment of intermittent claudication: a critical analysis of the methods and findings of published clinical trials, 1965-1985. Br J Clin Pharmacol. 1988;26569- 576
Link to Article
Kriessmann  A Peripheral arterial occlusive disease: conservative treatment of intermittent claudication. J Cardiovasc Pharmacol. 1990;16(suppl 3)S72- S74
Link to Article
Radack  KWydersky  RJ Conservative management of intermittent claudication. Ann Intern Med. 1990;113135- 146
Link to Article
Rao  CR Linear Statistical Inference and Its Applications.  New York, NY John Wiley & Sons Inc1973;389- 391
Ekroth  RDahllöf  AGGundevall  BHolm  JSchersten  T Physical training of patients with intermittent claudication: indications, methods, and results. Surgery. 1978;84640- 643
Sorlie  DMyhre  K Effects of physical training in intermittent claudication. Scand J Clin Lab Invest. 1978;38217- 222
Link to Article
Kiesewetter  HJung  FBlume  JBulling  BGerhards  M Conservative drug therapy and walking exercise in stage IIb peripheral arterial occlusion disease. Klin Wochenschr. 1986;641061- 1069
Carter  SAHamel  ERPaterson  JMSnow  CJMymin  D Walking ability and ankle systolic pressures: observations in patients with intermittent claudication in a short-term walking exercise program. J Vasc Surg. 1989;10642- 649
Link to Article
Andriessen  MPBarendsen  GJWouda  AAde Pater  L The effect of six months intensive physical training on the circulation in the legs of patients with intermittent claudication. Vasa. 1989;1856- 62
Williams  LREkers  MACollins  PSLee  JF Vascular rehabilitation: benefits of a structured exercise/risk modification program. J Vasc Surg. 1991;14320- 326
Link to Article
Lepantalo  MSundberg  SGordin  A The effects of physical training and flunarizine on walking capacity in intermittent claudication. Scand J Rehabil Med. 1984;16159- 162
Jonason  TJonzon  BRingqvist  IÖman-Rydberg  A Effect of physical training on different categories of patients with intermittent claudication. Acta Med Scand. 1979;206253- 258
Link to Article
Clifford  PCDavies  PWHayne  JABaird  RN Intermittent claudication: is a supervised exercise class worth while? BMJ. 1980;2801503- 1505
Link to Article
Jonason  TRingqvist  I Effect of training on the post-exercise ankle blood pressure reaction in patients with intermittent claudication. Clin Physiol. 1987;763- 69
Link to Article
Hiatt  WRNawaz  DRegensteiner  JGHossack  KF The evaluation of exercise performance in patients with peripheral vascular disease. J Cardiopulm Rehabil. 1988;12525- 532
Link to Article
Ruell  PAImperial  ESBonar  FJThursby  PFGass  GC The effect of physical training on walking tolerance and venous lactate concentration. Eur J Appl Physiol. 1984;52420- 425
Link to Article
Boyd  CEBird  PJTeates  CDWellons  HAMacDougall  MAWolfe  LA Pain free physical training in intermittent claudication. J Sports Med. 1984;24112- 122
Diehm  CKuhn  AStrauss  RMuller  CHKubler  W Effects of regular physical training in a supervised class and additional intravenous prostaglandin E1 and naftidrofuryl infusion therapy in patients with intermittent claudication: a controlled study. Vasa. 1989;28(suppl)26- 30
Andriessen  MPHMBarendsen  GJWouda  AADe Pater  L Changes of walking distance in patients with intermittent claudication during six months intensive physical training. Vasa. 1989;1863- 68
Holm  JSchersten  T Exercise training of patients with intermittent claudication. Scand J Rehabil Med. 1983;9(suppl)20- 26
Alpert  JSLarsen  OELassen  NA Exercise and intermittent claudication: blood flow in the calf muscle during walking studied by xenon-133 clearance method. Circulation. 1969;39353- 359
Link to Article
Wisham  LHAbramson  ASEbel  A Value of exercise in peripheral arterial disease. JAMA. 1953;510- 12
Link to Article
Jonason  TRingqvist  I Prediction of the effect of training on the walking tolerance in patients with intermittent claudication. Scand J Rehabil Med. 1987;1947- 50
Feinberg  RLGregory  RTWheeler  JR  et al.  The ischemic window: a method for the objective quantitation of the training effect in exercise therapy for intermittent claudication. J Vasc Surg. 1992;16244- 250
Link to Article
McAllister  FF The fate of patients with intermittent claudication managed nonoperatively. Am J Surg. 1976;132593- 595
Link to Article
Myhre  KSorlie  DG Physical activity and peripheral atherosclerosis. Scand J Soc Med Suppl. 1982;29195- 201
Rosetzsky  AStruckmann  JMathiesen  FR Minimal walking distance following exercise treatment in patients with arterial occlusive disease. Ann Chir Gynaecol. 1985;74261- 264
Pancera  PPrior  MZannoni  MLucchese  LDe Marchi  SArosio  E Micro- and macrocirculatory, and biohumoral changes after a month of physical exercise in patients with intermittent claudication. Scand J Rehabil Med. 1995;2773- 76
Skinner  JSStrandness  DE  Jr Exercise and intermittent claudication: effect of physical training. Circulation. 1967;3623- 29
Link to Article
Hall  JABarnard  RJ The effects of an intensive 26-day program of diet and exercise on patients with peripheral vascular disease. J Cardiac Rehabil. 1982;2569- 574
Pritikin  NKern  JKaye  SM Diet and exercise as a total therapeutic regimen for the rehabilitation of patients with severe peripheral vascular disease. Arch Phys Med Rehabil. 1975;56558
Zetterqvist  S The effect of active training on the nutritive blood flow in exercising ischemic legs. Scand J Clin Lab Invest. 1970;25101- 111
Link to Article
Skinner  JSStrandness  DE Exercise and intermittent claudication: effect of repetition and intensity of exercise. Circulation. 1967;3615- 22
Link to Article
Blumchen  GLandry  FKiefer  HSchlosser  V Hemodynamic response of claudicating extremities: evaluation of a long range exercise program. Cardiology. 1970;55114- 127
Link to Article
Jonason  TRingqvist  IÖman-Rydberg  A Home-training of patients with intermittent claudication. Scand J Rehabil Med. 1981;13137- 141
Johnson  ECVoyles  WFAtterbom  HAPathak  DSutton  MFGreene  ER Effects of exercise training on common femoral artery blood flow in patients with intermittent claudication. Circulation. 1989;80(suppl III)III-59- III-72
Link to Article
Perkins  JMTCollin  JCreasy  TSFletcher  EWLMorris  PJ Exercise training versus angioplasty for stable claudication: long and medium term results of a prospective, randomised trial. Eur J Vasc Endovasc Surg. 1996;11409- 413
Link to Article
Lundgren  FDahllöf  AGSchersten  TBylund-Fellenius  AC Muscle enzyme adaption in patients with peripheral arterial insufficiency: spontaneous adaption, effect of different treatments and consequences on walking performance. Clin Sci. 1989;77485- 493
Holm  JDahllöf  AGBjorntorp  PSchersten  T Enzyme studies in muscles of patients with intermittent claudication: effect of training. Scand J Clin Lab Invest. 1973;128(suppl)201- 205
Larsen  OALassen  NA Effect of daily muscular exercise in patients with intermittent claudication. Scand J Clin Lab Invest 1966;99(suppl)168- 171
Cronenwett  JLWarner  KGZelenock  GB  et al.  Intermittent claudication: current results of nonoperative management. Arch Surg. 1984;119430- 436
Link to Article
Regensteiner  JGSteiner  JFHiatt  WR Exercise improves functional status in patients with peripheral arterial disease. J Vasc Surg. 1996;23104- 115
Link to Article
Lundgren  FDahllöf  AGLundholm  KSchersten  TVolkmann  R Intermittent claudication: surgical reconstruction or physical training? a prospective randomized trial of treatment efficiency. Ann Surg. 1989;209346- 355
Link to Article
Mannarino  EPasqualini  LInnocente  SScricciolo  VRignanese  ACiuffetti  G Physical training and antiplatelet treatment in stage II peripheral arterial occlusive disease: alone or combined? Angiology. 1991;42513- 521
Link to Article
Dahllöf  AGBjorntorp  PHolm  JSchersten  T Metabolic activity of skeletal muscle in patients with peripheral arterial insufficiency: effect of physical training. Eur J Clin Invest. 1974;49- 15
Link to Article
Hiatt  WRWolfel  EEMeier  RHRegensteiner  JG Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Circulation. 1994;901866- 1874
Link to Article
Larsen  OALassen  NA Effect of daily muscular exercise in patients with intermittent claudication. Lancet. 1966;21093- 1096
Link to Article
Hiatt  WRRegensteiner  JGHargarten  MEWolfel  EEBrass  EP Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation. 1990;81602- 609
Link to Article
Dahllöf  AGHolm  JSchersten  TSivertsson  R Peripheral arterial insufficiency: effect of physical training on walking tolerance, calf blood flow, and blood flow resistance. Scand J Rehabil Med. 1976;819- 26
Mannarino  EPasqualini  LMenna  MMaragoni  GOrlandi  U Effects of physical training on peripheral vascular disease: a controlled study. Angiology. 1989;405- 10
Link to Article
Ernst  EEWMatrai  A Intermittent claudication, exercise, and blood rheology. Circulation. 1987;761110- 1114
Link to Article
Ericsson  BHaeger  KLindell  SE Effect of physical training on intermittent claudication. Angiology. 1970;21188- 192
Link to Article
Jonason  TBergstrom  R Cessation of smoking in patients with intermittent claudication. Acta Med Scand. 1987;221253- 260
Link to Article
Smith  IFranks  PJGreenhalgh  RMPoulter  NRPowell  JT The influence of smoking cessation and hypertriglyceridaemia on the progression of peripheral arterial disease and the onset of critical ischaemia. Eur J Vasc Endovasc Surg. 1996;11402- 408
Link to Article
Vasli  LRFoss  OP Serum thiocyanate, smoking habits and smoking cessation trial in patients with peripheral atherosclerosis. Scand J Clin Lab Invest. 1987;47399- 403
Link to Article
Porter  JMBaur  GM Pharmacologic treatment of intermittent claudication. Surgery. 1982;92966- 971
Reich  TGillings  D Effects of pentoxifylline on severe intermittent claudication. Angiology. 1987;38651- 656
Link to Article
Reich  TCutler  BCLee  BY  et al.  Pentoxifylline in the treatment of intermittent claudication of the lower limbs. Angiology. 1984;35389- 395
Link to Article
Porter  JMCutler  BSLee  BY  et al.  Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. Am Heart J. 1982;10466- 72
Link to Article
Gillings  DKoch  GReich  TStager  WJ Another look at the pentoxifylline efficacy data for intermittent claudication. J Clin Pharmacol. 1987;27601- 609
Link to Article
Roeren  TLeVeen  RFNugent  L Photoplethysmographic documentation of improved microcirculation after pentoxifylline therapy. Angiology. 1988;39929- 933
Link to Article
AbuRahma  AFWoodruff  BA Effects and limitations of pentoxifylline therapy in various stages of peripheral vascular disease of the lower extremity. Am J Surg. 1990;160266- 270
Link to Article
Poggesi  LScarti  LBoddi  MMasotti  GSerneri  GG Pentoxifylline treatment in patients with occlusive peripheral arterial disease: circulatory changes and effects on prostaglandin synthesis. Angiology. 1985;36628- 637
Link to Article
Pignoli  PCiccolo  FVilla  VLongo  T Comparative evaluation of buflomedil and pentoxiphylline in patients with peripheral arterial occlusive disease. Curr Ther Res. 1985;37596- 606
Chacon-Quevedo  AEguaras  MGCalleja  F  et al.  Comparative evaluation of pentoxifylline, buflomedil, and nifedipine in the treatment of intermittent claudication of the lower limbs. Angiology. 1994;45647- 653
Link to Article
Perhoniemi  VSalmenkivi  KSundberg  SJohnsson  RGordin  A Effects of flunarizine and pentoxifylline on walking distance and blood rheology in claudication. Angiology. 1984;35366- 372
Link to Article
Feine-Haake  G Assessment of the therapeutic efficacy of pentoxifylline (Trental): a double-blind trial in geriatric patients with vascular disorder. Pharmatherapeutica. 1983;3(suppl 1)46- 51
Accetto  B Beneficial hemorheologic therapy of chronic peripheral arterial disorders with pentoxifylline: results of a double-blind study versus vasodilator-nylidrin. Am Heart J. 1982;103864- 869
Link to Article
Trübestein  GTrübestein  RDuong  QD Comparative evaluation of the effectiveness of buflomedil and pentoxiphylline in patients with arterial occlusive disease. Angiology. 1981;32705- 709
Link to Article
Mashiah  APatel  PSchraibman  IGCharlesworth  D Drug therapy in intermittent claudication: an objective assessment of the effects of three drugs in patients with intermittent claudication. Br J Surg. 1978;65342- 345
Link to Article
Deutschinoff  AGrozdinsky  L Rheological and anticoagulant therapy of patients with chronic peripheral occlusive arterial disease (COAD). Angiology. 1987;38351- 358
Link to Article
Dettori  AGPini  MMoratti  A  et al.  Acenocoumarol and pentoxifylline in intermittent claudication: a controlled clinical study. Angiology. 1989;40237- 248
Link to Article
Ernst  EKollar  LResch  KL Does pentoxifylline prolong the walking distance in exercised claudicants? a placebo-controlled double-blind trial. Angiology. 1992;43121- 125
Link to Article
Lindgärde  FJelnes  RBjorkman  H  et al.  Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Circulation. 1989;801549- 1556
Link to Article
Donaldson  DRHall  TJKester  RCRamsden  CWWiggins  PA Does oxpentifylline (Trental) have a place in the treatment of intermittent claudication? Curr Med Res Opin. 1984;935- 40
Link to Article
Di Perri  TGuerrini  M Placebo controlled double blind study with pentoxifylline of walking performance in patients with intermittent claudication. Angiology. 1983;3440- 45
Link to Article
Reilly  DTQuinton  DNBarrie  WW A controlled trial of pentoxifylline (Trental 400) in intermittent claudication: clinical, haemostatic and rheological effects. N Z Med J. 1987;100445- 447
Gallus  ASGleadow  FDupont  P  et al.  Intermittent claudication: a double-blind crossover trial of pentoxifylline. Aust N Z J Med. 1985;15402- 409
Link to Article
Bollinger  AFrei  CH Double-blind trial of pentoxifylline against placebo in patients with intermittent claudication. Pharmatherapeutica. 1977;1557- 561
Volker  D Treatment of artheriopathies with pentoxifylline (Trental 400): results of a double-blind study. Pharmatherapeutica. 1983;3(suppl 1)136- 142
Tonak  JKnecht  HGroitl  H Treatment of circulatory disturbances with pentoxifylline: double-blind study with Trental. Pharmatherapeutica. 1983;3(suppl 1)126- 135
Rudofsky  GHaussler  KFKünkel  HP  et al.  Intravenous treatment of chronic peripheral occlusive arterial disease: a double-blind, placebo-controlled, randomized, multicenter trial of pentoxifylline. Angiology. 1989;40639- 649
Link to Article
Scheffler  Pde la Hamette  DGross  JMueller  HSchieffer  H Intensive vascular training in stage IIb in peripheral arterial occlusive disease: the additive effects of intravenous prostaglandin E1 or intravenous pentoxifylline during training. Circulation. 1994;90818- 822
Link to Article
Waters  KJCraxford  ADChamberlain  J The effect of naftidrofuryl (Praxilene) on intermittent claudication. Br J Surg. 1980;67349- 351
Link to Article
Ruckley  CVCallam  MJFerrington  CMPrescott  RJ Naftidrofuryl for intermittent claudication: a double-blind controlled trial. BMJ. 1978;1620
Rosas  GCerdeyra  CLucas  MAParano  JRVilla  JJ Comparison of safety and efficacy of buflomedil and naftidrofuryl in the treatment of intermittent claudication. Angiology. 1981;32291- 297
Link to Article
Karnik  RValentin  AStöllberger  CSlany  J Effects of naftidrofuryl in patients with intermittent claudication. Angiology. 1988;39234- 240
Link to Article
Adhoute  GBacourt  FBarral  M  et al.  Naftidrofuryl in chronic arterial disease: results of a six month controlled multicenter study using naftidrofuryl tablets 200 mg. Angiology. 1986;37160- 167
Link to Article
Trübestein  GBöhme  HHeidrich  H  et al.  Naftidrofuryl in chronic arterial occlusive disease: results of a controlled multicenter study. Angiology. 1984;35701- 708
Link to Article
Adhoute  GAndreassian  HBoccalon  M  et al.  Treatment of stage II chronic arterial disease of the lower limbs with the serotoninergic antagonist naftidrofuryl: results after six months of a controlled multicenter study. J Cardiovasc Pharmacol. 1990;16(suppl 3)S75- S80
Link to Article
Moody  APAl-Khaffaf  HSLehert  PHarris  PLCharlesworth  D An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl. J Cardiovasc Pharmacol. 1994;23(suppl 3)S44- S47
Link to Article
Clyne  CACGalland  RBFox  MJGustave  RJantet  GHJamieson  CW A controlled trial of naftidrofuryl (Praxilene) in the treatment of intermittent claudication. Br J Surg. 1980;67347- 348
Link to Article
Patterson  RBPinto  BMarcus  BColucci  ABraun  TRoberts  M Value of a supervised exercise program for the therapy of arterial claudication. J Vasc Surg. 1997;25312- 319
Link to Article
Regensteiner  JGMeyer  TJKrupski  WCCranford  LSHiatt  WR Hospital- vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease. Angiology. 1997;48291- 300
Link to Article
Girolami  BBernardi  EKoelemay  MPrandoni  PGirolami  APrins  MH Pharmacological treatment of peripheral arterial occlusive disease (Fontaine's stage II): a meta-analysis of randomised clinical trials [abstract]. Thromb Haemost. 1995;61386
Hood  SCMoher  DBarber  GG Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. CMAJ. 1996;1551053- 1059
Grégorie  GDerderian  FLe Lorier  J Selecting the language of the publications included in a meta-analysis: is there a Tower of Babel bias? J Clin Epidemiol. 1995;48159- 163
Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

* * SCHEDULED MAINTENANCE * *

Our websites may be periodically unavailable between midnight and 04:00 ET Thursday, July 10th, for regularly scheduled maintenance.

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 129

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles