Antithrombotic Drugs in the Primary Medical Management of Intermittent Claudication: A Meta-analysis

Summary Background. There is no consensus on the efficacy of the antithrombotic drugs available for patients with intermittent claudication. Methods. A Medline and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports or trials without clinical outcomes were excluded. Included studies were graded as level 1 (randomised and double- or assessor-blind), level 2 (open randomised), or level 3 (non-randomised comparative). Mortality, cerebro- or cardiovascular events, amputations, arterial occlusions or number of revascularization procedures performed in the lower limbs, pain-free and total walking distance, ankle brachial index and calf blood flow, were the main outcomes considered. When feasible, end of treatment results, either continuous or binary, were combined with appropriate statistical methods. Results. Mortality was significantly decreased by ticlopidine compared to placebo (common odds ratio 0.68, 95% C.I., 0.49 - 0.95); clopidogrel decreased vascular events in comparison to aspirin (odds ratio 0.76, 95% C.I., 0.63 - 0.92) in level 1 studies. Arterial occlusions and the number of revascularization procedures performed were statistically significantly decreased by aspirin and ticlopidine, respectively. A small but statistically significant improvement in pain-free walking distance was determined by picotamide, indobufen, low molecular weight heparins, sulodexide and defibrotide, in small studies. Conclusions. Clopidogrel and ticlopidine do reduce clinically important events in patients with intermittent claudication and could be added to the primary medical treatment of these patients. The use of aspirin in these patients cannot be based on direct evidence, but only on analogy with coronary and cerebral atherosclerosis, where it has documented efficacy. Other antithrombotic drugs were not properly evaluated in patients with intermittent claudication.

Download Full-text

Ventilatory threshold is related to walking tolerance in patients with intermittent claudication

VASA ◽

10.1024/0301-1526/a000203 ◽

2012 ◽

Vol 41 (4) ◽

pp. 275-281 ◽

Cited By ~ 3

Author(s):

da Rocha Chehuen ◽

G. Cucato ◽

P. dos Anjos Souza Barbosa ◽

A. R. Costa ◽

M. Ritti-Dias ◽

...

Keyword(s):

Blood Flow ◽

Oxygen Uptake ◽

Intermittent Claudication ◽

Lower Limb ◽

Ventilatory Threshold ◽

Reactive Hyperemia ◽

Ankle Brachial Index ◽

Metabolic Parameters ◽

Walking Distance ◽

The Relationship

Background: This study assessed the relationship between lower limb hemodynamics and metabolic parameters with walking tolerance in patients with intermittent claudication (IC). Patients and methods: Resting ankle-brachial index (ABI), baseline blood flow (BF), BF response to reactive hyperemia (BFRH), oxygen uptake (VO2), initial claudication distance (ICD) and total walking distance (TWD) were measured in 28 IC patients. Pearson and Spearman correlations were calculated. Results: ABI, baseline BF and BF response to RH did not correlate with ICD or TWD. VO2 at first ventilatory threshold and VO2peak were significantly and positively correlated with ICD (r = 0.41 and 0.54, respectively) and TWD (r = 0.65 and 0.71, respectively). Conclusions: VO2peak and VO2 at first ventilatory threshold, but not ABI, baseline BF and BFHR were associated with walking tolerance in IC patients. These results suggest that VO2 at first ventilatory threshold may be useful to evaluate walking tolerance and improvements in IC patients.

Download Full-text

The effects of exercise training on muscle oxygenation of patients with intermittent claudication

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.349 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

P Chatzinikolaou ◽

N Cornelis ◽

J Claes ◽

R Buys ◽

I Fourneau ◽

...

Keyword(s):

Intermittent Claudication ◽

Near Infrared ◽

Saturation Index ◽

Ankle Brachial Index ◽

Muscle Oxygenation ◽

Lower Limbs ◽

Current Evidence ◽

Test Time ◽

Treadmill Test ◽

Walking Capacity

Abstract Funding Acknowledgements Type of funding sources: None. Background. Intermittent claudication (IC) is characterized by a cramp-like pain during walking caused by insufficient blood flow to the lower limbs during exercise. The walking impairment caused by IC can lead to a vicious cycle of physical inactivity, decreased quality of life and progression of cardiovascular risk factors. Although current evidence supports the benefits of walking training to increase walking capacity, little is known about its effect on muscle oxygenation in this population. Purpose. The aim of this study was to investigate the effects of a hybrid 12-week walking program (combined center- and home-based walking) on muscle oxygenation of IC patients. Methods. Thirty-seven patients with IC were enrolled of which 33 completed follow-up measurements (age 71 ± 9 yrs, body mass index 26 ± 4 kg/m2, ankle brachial index (ABI) 0.7 ± 0.2) after the 12-week intervention. Outcome measures were pain-free walking capacity (PFWC), maximal walking capacity (MWC) and calf muscle oxygenation, respectively evaluated using a submaximal treadmill test, a Gardner treadmill test and near-infrared spectroscopy (NIRS). Results. After the 12-week intervention, significantly higher values (reported as median and interquartiles) for PFWC (162 m [122, 217] to 272 m [150, 401]; p < 0.001) and MWC (458 m [260, 638] to 611 m [333, 840]; p < 0.001) were observed. As shown in Table 1, NIRS data measured during the submaximal walking test showed an increased availability of oxygenated hemoglobin (p = 0.048) and decreased deoxyhemoglobin (p = 0.013), while total hemoglobin remained unchanged after the 12-week intervention. During the Gardner test, time to reach minimum tissue saturation index (TSI%) increased (p < 0.001), yet no change was noted on minimum TSI during exercise, despite increased MWC. Despite a trend towards faster recovery times, no significant changes were observed after the 12-week intervention. Conclusion. Hybrid walking exercise therapy improves deoxygenation kinetics and walking capacity in IC patients. Increased availability of oxygenated hemoglobin might underly the improvement in walking capacity.

Download Full-text

Indikationen und Limitationen des Gehtrainings bei Patienten mit Cladicatio intermittens

VASA ◽

10.1024/0301-1526.31.1.23 ◽

2002 ◽

Vol 31 (1) ◽

pp. 23-27 ◽

Cited By ~ 1

Author(s):

Takashi Ohta ◽

Sugimoto ◽

Takeuchi ◽

Hosaka ◽

Ishibashi

Keyword(s):

Exercise Training ◽

Intermittent Claudication ◽

Recovery Time ◽

Ankle Brachial Index ◽

Walking Distance ◽

Hemodynamic Parameters ◽

Arterial Reconstruction ◽

Arteriosclerosis Obliterans ◽

Degree Of Satisfaction ◽

Selection Of

Background: The selection of candidates for exercise training among patients with intermittent claudication is still a matter of debate. Patients and methods: Forty-nine patients with intermittent claudication due to arteriosclerosis obliterans were tested. Forty-six patients were men and 3 were women, with an average age of 65 years (range, 46 to 76 years). The patients walked on a treadmill at 2.4 km/h on a 12% upgrade followed by an appropriate period of rest for 30 minutes twice a day during a 3-week hospitalization. Programs were individualized for each patient. Four parameters were assessed after exercise training: (1) Ankle-brachial index (ABI) at rest, (2) Fall in ABI after 40 m of treadmill walking (ABI Fall 40), (3) the recovery time (RT 40) required for the ABI to return to resting levels after 40 m of walking, and (4) the maximal walking distance (MWD) on the treadmill. Results: The average ABI at rest before the 3-week training period was 0.60 ± 0.02 (mean ± SE), and after training it was 0.62 ± 0.02. There was a small although not statistically significant increase in the ABI after training. This increase in the ABI did not exceed 0.21. The average ABI Fall 40 before training was 0.36 ± 0.01, and after training it was 0.30 ± 0.02. The average RT 40 before training was 9.9 ± 0.8 min, and after training it was 6.2 ± 0.6 min. There were significant decreases in the ABI Fall 40 and RT 40 after training (p < 0.01 and p < 0.001, respectively). The MWD increased after training in 48 of the 49 patients. The average MWD increased from 134 ± 13 m to 226 ± 32 m after training (p < 0.001). The occlusion levels did not influence the results as training effects and hemodynamic parameters. Fourteen of 49 patients desired arterial reconstruction after exercise training. Conclusions: Patients with shorter RT 40’s before training achieved greater increases in the MWD after training. In patients with an RT 40 under 12 min, exercise training is indicated. However, there is some discrepancy between the increase in MWD and the degree of satisfaction in individual patients.

Download Full-text

The Impact of Walking Exercises and Resistance Training upon the Walking Distance in Patients with Chronic Lower Limb Ischaemia

BioMed Research International ◽

10.1155/2016/7515238 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Maria Szymczak ◽

Grzegorz Oszkinis ◽

Marian Majchrzycki

Keyword(s):

Resistance Training ◽

Intermittent Claudication ◽

Rehabilitation Program ◽

Lower Limbs ◽

Walking Distance ◽

Group Training ◽

Limb Ischaemia ◽

Walking Test ◽

Resistance Exercises ◽

The Impact

Objective. The objective of this paper is to compare the impact of supervised walking and resistance training upon the walking distance in PAD patients. Materials and Methods. The examination involved 50 PAD patients at the 2nd stage of the disease according to Fontaine’s scale. The participants were randomly allocated to two groups: one exercising on the treadmill (n=24) and one performing resistance exercises of lower limbs (n=26). Results. The 12-week program of supervised rehabilitation led to a significant increase in the intermittent claudication distance measured both on the treadmill and during the 6-minute walking test. The group training on the treadmill showed a statistically significant increase of the initial claudication distance (ICD) and the absolute claudication distance (ACD) measured on the treadmill, as well as of ICD and the total walking distance (TWD) measured during the 6-minute walking test. Within the group performing resistance exercises, a statistically significant improvement was observed in the case of parameters measured on the treadmill: ICD and ACD. Conclusions. The supervised rehabilitation program, in the form of both walking and resistance exercises, contributes to the increase in the intermittent claudication distance. The results obtained in both groups were similar.

Download Full-text

Physiotherapeutic intervention in peripheral arterial disease by functional hyperemia in diabetic patients

Fisioterapia em Movimento ◽

10.1590/0103-5150.028.004.ao10 ◽

2015 ◽

Vol 28 (4) ◽

pp. 731-740

Author(s):

Cristiane Wichnieski ◽

Flávia Natacha Salvatori Kirchhof ◽

Pedro Cezar Beraldo ◽

Luiz Bertassoni Neto ◽

Christian Campos Jara

Keyword(s):

Peripheral Arterial Disease ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Lower Limbs ◽

Walking Distance ◽

Diabetic Patients ◽

Functional Hyperemia ◽

Peripheral Vascular ◽

Vascular Disorders ◽

Peripheral Arterial

Abstract Introduction : Diabetes Mellitus (DM) is conceptualized as a public health problem with varying degrees of morbidity. The physical and functional alternatives for the treatment of circulatory complications of diabetes, such as intermittent claudication, are poorly explored. This indicates the need to search for ancillary techniques that can be used in the physical therapy treatment of diabetic patients. Objective : To investigate the effects of functional hyperemia on peripheral arterial disease in patients with diabetes. Materials and methods: This study was conducted with a group of five volunteers from the Diabetics Association of Parana (Associação Paranaense do Diabético , APAD ), who suffered from peripheral vascular disorders in the lower limbs. All subjects attended 10 sessions (twice weekly). Functional hyperemia was induced by programmed exercise therapy that consisted of walking on a treadmill. Results : There was a significant increase in mean activity time (F9,36 = 13.710; p < 0.001 ), mean walking distance (F9,36 = 27.689 ; p < 001), and mean speed (F9,36 = 15.638 ; p < .001). No statistically significant differences in the ankle-brachial index were noted. Conclusion : There was a significant increase in walking distance, time, and speed for diabetic subjects. Our findings indicate the importance of physical therapists in the supervised treatment of peripheral vascular disorders in diabetic patients.

Download Full-text

Simple assessment of quality of life and lower limb functional capacity during cilostazol treatment – results of the SHort-tERm cIlostazol eFFicacy and quality of life (SHERIFF) study

VASA ◽

10.1024/0301-1526/a000845 ◽

2020 ◽

Vol 49 (3) ◽

pp. 235-242 ◽

Cited By ~ 1

Author(s):

Katalin Farkas ◽

Endre Kolossváry ◽

Zoltán Járai

Keyword(s):

Quality Of Life ◽

Clinical Practice ◽

Intermittent Claudication ◽

Functional Capacity ◽

Lower Limb ◽

Ankle Brachial Index ◽

Walking Distance ◽

Treatment Results ◽

Walking Capacity

Summary: Background: Symptomatic peripheral arterial disease (intermittent claudication) is a major cause of disability and mobility loss in older men and women and thus has a significant negative impact on the patients’ quality of life. Both surgical and endovascular revascularization procedures and noninvasive medical therapies, such as supervised training and drug treatment, can improve walking capacity. Cilostazol is the only drug having a class I (level of evidence A) recommendation for the treatment of intermittent claudication (IC). The aim of this study was to evaluate the effect of three-month cilostazol treatment on the health-related quality of life and on the lower limb functional capacity in patients with IC in the clinical practice. Patients and methods: The study was a multicenter, non-interventional trial, performed in Hungary in 2018. 812 PAD patients (Fontaine II stage, mean age: 67.17 years, male/female: 58.25/41.75 %) were enrolled, who received cilostazol (50 or 100 mg b.i.d.) for 3 months. 802 patients completed the study. Quality of life was evaluated with the EQ-5D-3L questionnaire functional capacity with the WELCH (Walking Estimated-Limitation Calculated by History) questionnaire. Pain-free and maximal walking distance, ankle-brachial index (ABI) were measured at baseline and after 3-month treatment. Results: Upon conclusion of the study, the EQ-5D-3L index improved (baseline: –0.46 ± 0.22, 3rd month: –0.26 ± 0.18; p < 0.0001) and there was a significant increase in the WELCH score as well (19 ± 14, 31 ± 18; respectively, p < 0.0001). Both pain-free and maximal walking distance improved significantly by 54.52 % (median: 53.85 %) and 42.5 % (median: 34.68 %); respectively (p < 0.001). Adverse events occurred in 10 patients, 1 patient stopped cilostazol treatment because of side effects. Conclusions: Three months cilostazol treatment significantly improved quality of life and lower limb functional capacity in patients with intermittent claudication. The WELCH questionnaire is a useful tool for the evaluation of intermittent claudication treatment in the clinical practice.

Download Full-text

Exercise training for intermittent claudication: a narrative review and summary of guidelines for practitioners

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2020-000897 ◽

2020 ◽

Vol 6 (1) ◽

pp. e000897

Author(s):

Amy E Harwood ◽

Sean Pymer ◽

Lee Ingle ◽

Patrick Doherty ◽

Ian C Chetter ◽

...

Keyword(s):

Exercise Training ◽

Intermittent Claudication ◽

Mode Of Delivery ◽

Lower Limbs ◽

Walking Distance ◽

Walking Ability ◽

Aerobic Activity ◽

Supervised Exercise ◽

Home Based ◽

Exercise Programmes

Peripheral artery disease (PAD) is caused by atherosclerotic narrowing of the arteries supplying the lower limbs often resulting in intermittent claudication, evident as pain or cramping while walking. Supervised exercise training elicits clinically meaningful benefits in walking ability and quality of life. Walking is the modality of exercise with the strongest evidence and is recommended in several national and international guidelines. Alternate forms of exercise such as upper- or lower-body cycling may be used, if required by certain patients, although there is less evidence for these types of programmes. The evidence for progressive resistance training is growing and patients can also engage in strength-based training alongside a walking programme. For those unable to attend a supervised class (strongest evidence), home-based or ‘self-facilitated’ exercise programmes are known to improve walking distance when compared to simple advice. All exercise programmes, independent of the mode of delivery, should be progressive and individually prescribed where possible, considering disease severity, comorbidities and initial exercise capacity. All patients should aim to accumulate at least 30 min of aerobic activity, at least three times a week, for at least 3 months, ideally in the form of walking exercise to near-maximal claudication pain.

Download Full-text

PREVENTION OF SYSTEMIC THROMBO-EMBOLISM IN PATIENTS WITH ATHEROSCLEROTIC INTERMITTENT CLAUDICATION

10.1055/s-0038-1643461 ◽

1987 ◽

Author(s):

J P Boissel ◽

J C Peyrieux ◽

J M Destors ◽

M Lievre ◽

P Moleur

Keyword(s):

Intermittent Claudication ◽

Selection Criteria ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Walking Distance ◽

Vascular Events ◽

Secondary Objective ◽

Cardio Vascular ◽

Lost To Follow Up

Ticlopidine (TI), an anti-aggregating agent which inhibits the ADP-pathway has been tested in patients with intermittent claudication (IC) in 11 randomized clinical trials (RTCs).As expected, a significant reduction of cardio-vascular events (CVE) due to systemic thrombo-embolism was observed in the 2 larger. Reduction in the number of CVE due to systemic thromboembolism in any arterial bed was observed. This prompted us to confirm the hypothesis that TI was beneficial in preventing systemic thrombo-embolism in patients with IC. Four RCTs from the 11 were blindly selected on the basis on pre-set selection criteria : placebo controlled, more than 1 month duration, , less than 5 % lost-to-follow-up (index of quality), parallel groups, proven atherosclerotic disease. Meta-analysis was performed with 5 statistical methods which gave consistent findings : as compared to 311 patients on placebo, the 301 patients on TI have had a 66 % reduction in the number of CVE during the 6 months of follow-up (9.0 % to 3 % , p = 0.002). Walking distance, a secondary objective of meta-analysis, doubled in 42 % of the patients on TI as against 27 % (p = 0.0005).It was concluded that TI 250 mg b.i.d. prevents CVE in patients with atherosclerotic IC.

Download Full-text

Is It Possible to Reduce the Risk of Cardiovascular Events in Subjects Suffering from Intermittent Claudication of the Lower Limbs?

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646882 ◽

1989 ◽

Vol 62 (02) ◽

pp. 681-685 ◽

Cited By ~ 37

Author(s):

J P Boissel ◽

J C Peyrieux ◽

J M Destors

Keyword(s):

Intermittent Claudication ◽

Cardiovascular Events ◽

Antiplatelet Agent ◽

Lower Limbs ◽

High Risk Population ◽

Study Medication ◽

Vascular Events ◽

Double Blind ◽

Cardio Vascular

SummaryThis study meta-analysed randomized, double-blind, placebo controlled trials in patients with intermittent claudication of the lower limbs comparing ticlopidine to placebo in order to test the hypothesis that the drug, a pure antiplatelet agent, is able to reduce the incidence of thrombotic cardio-vascular events on atherosclerotic arteries in these patients. A highly significant reduction, from 9% to 3% (p ranging from 0.006 to 0.002), was observed for fatal or non-fatal cardio-vascular events in a total of 611 patients (301 with ticlopidine, 310 with placebo). The duration of follow-up ranged from 6 to 12 months. Side-effects, defined as withdrawal from study medication for any reason but death, cardio-vascular events or cancer, were 2.4 times more frequent in the ticlopidine treated patients as compared to placebo. We concluded that in this high risk population, prevention of cardio-vascular events is likely to be effective.

Download Full-text

Integrative therapy in patients with intermittent claudication

VASA ◽

10.1024/0301-1526/a000413 ◽

2015 ◽

Vol 44 (2) ◽

pp. 85-91

Author(s):

Erich Minar

Keyword(s):

Intermittent Claudication ◽

Modern Technology ◽

Walking Distance ◽

Interventional Treatment ◽

Therapeutic Concept ◽

Integrative Therapy ◽

Risk Factor Modification ◽

Supervised Exercise ◽

Main Challenge ◽

Exercise Programmes

The generally accepted first-line treatment in patients with intermittent claudication is risk factor modification, medical treatment and exercise training. In an era of reduced resources, the benefit of any further invasive intervention must be weighted against best conservative therapy for patients with claudication. According to some recent trials an integrative therapeutic concept combining best conservative treatment - including (supervised) exercise therapy - with endovascular therapy gives the best midterm results concerning walking distance and health-related quality of life. The improved mid- and long-term patency rate with use of modern technology further supports this concept. The conservative and interventional treatment strategy are more complimentary than competitive. The current main challenge is to overcome the economic barriers concerning the availability of exercise programmes.

Download Full-text