Blood flow restricted walking in patients suffering from intermittent claudication: a case series feasibility and safety study

Objectives:

To examine the feasibility and safety of blood flow restricted walking (BFR-W) in patients with intermittent claudication (IC). Moreover, to evaluate changes in objective performance-based and self-reported functioning following 12 weeks of BFR-W.

Materials and methods:

Sixteen patients with IC were recruited from two departments of vascular surgery. The BFR-W programme implied the application of a pneumatic cuff around the proximal part of the affected limb at 60% limb occlusion pressure in five intervals of 2 min, four times per week for 12 weeks. Feasibility was evaluated by adherence and completion rates of the BFR-W programme. Safety was evaluated by adverse events, ankle-brachial index (ABI) at baseline and follow-up, and pain on a numerical rating scale (NRS pain) before and 2 min after training sessions. Furthermore, changes in performance between baseline and follow-up were evaluated with the 30 seconds sit-to-stand test (30STS), the 6-minute walk test (6MWT) and the IC questionnaire (ICQ).

Results:

Fifteen out of 16 patients completed the 12-week BFR-W programme and adherence was 92.8% (95% CI: 83.4; 100%). One adverse event unrelated to the intervention was reported causing one patient to terminate the programme 2 weeks prematurely. Mean NRS pain 2 min following BFR-W was 1.8 (95% CI [1.7–2]). ABI, 30STS, 6MWT and ICQ score were improved at follow-up.

Conclusions:

BFR-W is feasible and appears to be safe in terms of completion rate, adherence to the training protocol, and adverse events in patients with IC. Further investigation of the effectiveness and safety of BFR-W compared to regular walking exercise is needed.

Introduction

Highlights

• Uncertainties: the present study warrants further investigation in a randomised controlled trial design, as the results suggest that patients can achieve clinically meaningful improvements in performance-based and self-reported function.

• Key feasibility findings: it is feasible and safe to perform blood flow restricted walking (BFR-W) in patients with intermittent claudication (IC).

• Implications: BFR-W seems to be a potentially effective treatment for patients with IC.

Peripheral artery disease (PAD) is characterised by atherosclerotic narrowing of the arteries in the lower limbs1 and has an estimated global prevalence of 5.6% in people aged 25 and over; prevalence is higher at older ages in high-income countries2. Intermittent claudication (IC) is a stage of PAD where the blood flow to the lower limbs is insufficient to accommodate the oxygen demand during low-intensity muscle work (i.e. walking). Thus, IC is associated with walking-related pain in the calves and, less frequently, the thighs and buttocks, negatively impacting the quality of life and work ability3–5.

Conservative treatment for IC is exercise6,7, where supervised walking exercise has proven effective in improving the ability to walk for longer time periods and cover longer distances before the occurrence of IC symptoms8–10. However, walking as a self-management strategy among patients with IC is known to be challenging11. Therefore, unsupervised exercise strategies to improve walking ability are difficult to implement12.

Studies in other patient groups (e.g. elderly and patients with knee osteoarthritis) have demonstrated that low-intensity blood flow restricted (BFR) exercise can improve lower limb function, endurance, and muscle strength13–17. BFR exercise combines low-intensity exercises with a pneumatic cuff applied to the proximal part of the lower limb to reduce the arterial blood flow to the extremity while blocking the venous outflow. BFR exercise has been suggested to improve aerobic capacity by increasing blood flow, the artery diameter, and the formation of capillaries18–22, but in patients with IC, the risk of deep venous thrombosis (DVT) has been a concern. However, no association has been reported between BFR exercise and increased cardiovascular morbidity23–26. Previous DVT incidence rates in studies with BFR exercise interventions have been reported to be 0.06% in clinical and healthy populations27.

Currently, no studies have investigated the effect of BFR exercise in patients with IC. We aimed to investigate the feasibility and safety of BFR walking (BFR-W) in patients with IC. Moreover, to evaluate changes in patients’ performance-based and self-reported functioning after an intervention period of 12 weeks of BFR-W.

Materials and methods

The present feasibility study is a two-centre prospective case series conducted at two departments of cardiothoracic and vascular surgery. The study was conducted in accordance with the Declaration of Helsinki. Approval was obtained from The Central Denmark Region Committees on Health Research Ethics (1-10-72-219-21) and the study was registered at the Central Denmark Region’s internal list of scientific projects (1-16-02-405-21). Data were administered according to the General Data Protection Regulation (GDPR). The study has been reported in line with the PROCESS 2020 criteria28. Patients were recruited consecutively from October 2021 to March 2022. A nurse or physiotherapist provided oral and written project information to patients in the outpatient clinics, and all patients gave written informed consent prior to inclusion.

Participants

Patients at least 18 years old with an ankle-brachial index (ABI) 0.8 or less and an ability to walk at least 200 m were invited from the outpatient clinics. Patients were excluded if one of the following criteria were present: Fontaine stage III (rest pain, mostly in the feet) or IV (necrosis and/or gangrene of the limb)5; limited walking capability resulting from other factors than PAD (e.g. amputation, use of wheelchairs, severe osteoarthritis); previous thrombosis; vascular lower limb surgery; and cognitive deficit (e.g. dementia). A total of 129 patients were assessed for eligibility; 51 were invited to participate, of which 16 accepted to be included (Fig. 1).

Figure 1.

Flowchart of patient enrolment. *Other reasons: transportation time (n=4), limited time to participate (n=4), prioritised other disabilities (n=3) and not comfortable with BFR-W (n=1). BFR-W, blood flow restricted walking.

Intervention

The patients followed a 12-week BFR-W programme four times/week. Each training session consisted of five rounds of 120 s of walking with concurrent BFR applied to the proximal part of the affected leg (BFR-leg) at 60% limb occlusion pressure (LOP), and 60 s of rest without BFR between rounds (Table 1). In the case of bilateral IC, the leg with the most severe symptoms was defined as the BFR-leg. During weeks one and two, patients were offered one supervised session per week, subsequently every other week for the remaining 10 weeks (weeks 3–12). The supervised sessions were performed as group sessions, allowing patients to share experiences and resolve queries regarding the intervention. Patients were asked to record all training sessions in individual training diaries.

Table 1.

Exercise variables

Variable
Limb occlusion pressure (%)	60
Cuff width (cm)	11.7
Duration in weeks	12
Sessions per week (n)	4
Intervals (n)	5
Duration (s)	120
Rest between sets (s)	60
Supervised sessions week 1–2 (n)	2
Supervised sessions weeks 3–12 (n)	4

Determination of occlusion pressure

LOP was determined with the patient seated on an examination table in a resting state with a pneumatic cuff (Occlude Aps, Aarhus, Denmark) at the most proximal part of the BFR-leg29. An Ultrasound Doppler (Edan SD3 Vascular Ultrasonic Pocket Doppler, EdanUSA, 2018) was placed posterior to the medial malleolus on the BFR-leg to identify the arterial pulse in the tibial posterior artery. The cuff was inflated to 100 mmHg and then the pressure was gradually increased by 20 mmHg until the arterial pulse was no longer detectable with the Ultrasound Doppler, which was defined as LOP30. If the patients experienced pain and discomfort at 60% LOP, the pressure was decreased by 20 mmHg (n=2)31.

Outcome measures

Primary outcome measures

The primary outcome measures related to the feasibility and safety of the BFR intervention included adherence to training sessions, completion rate, adverse events, decrease in ABI and exacerbation of pain. Adherence to training sessions was measured for each patient by the number of planned training sessions completed. More than 75% of completed sessions were a priori determined as good adherence. The completion rate was defined as the percentage of patients completing the 12-week BFR-W training programme. Adverse events were defined as unintended and unexpected injuries, symptoms or other events from inclusion until follow-up. ABI was measured at the outpatient clinic by a nurse or a medical doctor prior to baseline and at follow-up. ABI was determined by measuring the systolic pressure of both brachial arteries and both of the posterior tibial and dorsalis pedis arteries. The highest pressure of the two arteries for each ankle was then divided by the highest measured left or right brachial pressure to calculate an ABI value for each leg. No change or increase in ABI towards the normal range (0.9–1.4) indicated the high safety of the intervention32. Pain was reported by patients at each training session and recorded in training diaries. Patients rated their pain before and 2 min after exercise on a 10-point numerical rating scale (NRS) where 0=no pain and 10=worst imaginable pain33, categorised into three groups: ≤5: mild-to-acceptable pain; 6–7: moderate pain; and ≥8: severe pain34.

Secondary outcome measures

At baseline and follow-up, patients completed the IC questionnaire (ICQ) and two physical performance tests: the 30-second sit-to-stand test (30STS) and the 6-minute walk test (6MWT). ICQ is a validated patient-reported outcome measure measuring health-related quality of life for patients with IC35. ICQ consists of 16 items and is scored from 0 (best) to 100 (worst). An improvement in health is indicated by a negative change in score from baseline to follow-up. 30STS measures lower extremity functional performance36. The 30STS was performed from a seated position (seat height 43 cm with no armrests) with the feet shoulder-width apart and arm crossed on the chest going into a standing position with hip and knee fully extended back into the seated position for a full repetition. The number of repetitions completed in 30 s was measured. Three practice repetitions were allowed before the trial. The 6MWT is a reliable measure of walking endurance and is performed by measuring the distance covered in 6 min37. The patients were permitted unlimited rest in a standing position during the trial. If the patient sat down to rest, the test was terminated. Patients walked indoors on a 10-m track. There was no communication between the assessor and patient during the test other than notifications for every minute that passed.

Statistical analysis

Descriptive statistics are presented as means with standard deviation (SD). Changes from baseline to follow-up were analysed with a paired t-test and presented as means with 95% confidence intervals [95% CI]. The normal distribution of outcome measures was assessed using the Shapiro–Wilks normality test. Data from the patients’ training diaries on adherence to the total number of training sessions were presented as n (%), and information about pain and exertion was presented as means [95% CI]. Adherence to the total number of training sessions was calculated for each patient as the number of sessions completed divided by the total number of sessions planned (n=48). Patients completing additional sessions will be indicated as exceeding 100% adherence. The completion rate was the number of patients completing 12 weeks of BFR-W divided by the number of patients included in the study (n=16). All statistical analyses were performed in the analysis software STATA 17.0 (StataCorp LLC, TX, USA).

Results

Patients

Patient characteristics are illustrated in Table 2. Sixteen of 51 eligible patients participated in the study intervention. Ten were males, the mean age was 67.2 (6.4) years, the mean BMI was 27.7 (5.3) kg/m²; 63% were former smokers and the mean ABI was 0.6 (0.12).

Table 2.

Baseline characteristics of patients prior to intervention (n=16)

Sex, male, n	10
Sex, female, n	6
Age in years, mean (SD)	67.2 (6.4)
Height in cm, mean (SD)	171.1 (8.1)
Weight in kg, mean (SD)	81.6 (18.7)
BMI (kg/m2), mean (SD)	27.7 (5.3)
Smoking status:
Never smoked, n	1
Former smoker, n	10
Occasional smoker, n	1
Regular smoker, n	3
Data missing, n	1
Index leg:
Right, n	9
Left, n	7
ABI, mean (SD)	0.6 (0.12)
60% LOP (mmHg), mean (SD)	127 (23)

ABI, ankle-brachial index; BMI, body mass index; LOP, limb occlusion pressure; SD, standard deviation.

Feasibility and safety

The mean adherence to the total number of planned training sessions was 93% [83; 100%] (Table 3). Fifteen of 16 patients demonstrated high adherence to the planned training sessions (Table 3). One adverse event is unrelated to the BFR-W programme was recorded (spinal fracture following a fall in the home), resulting in termination from the programme at the 10-week mark for this particular patient. Thus, 94% of patients completed all 12 weeks of BFR-W. No adverse effects related to the BFR intervention were recorded. The mean NRS pain before exercise was 0.9 [0.8–0.9] versus 1.8 [1.7–2] 2 min after exercise. NRS pain 5 or less 2 min after exercise was reported in 98% of the training sessions. The mean rate of perceived exertion was 2.8 [2.6–3.0]. Mean ABI measured at follow-up was 0.71(0.14), yielding a pre-to-post change of 0.11 [0.02–0.2] (Table 4).

Table 3.

Adherence to planned training sessions, completion rates, NRS for pain and exertion (n=16)

Id	Adherence, N (%)	Completed intervention	Pain 0–10 (before), Mean [95% CI]	Pain 0–10 (2 min after), Mean [95% CI]	Exertion 0–10, Mean [95% CI]
1	50 (104)	Yes	1 [–]	4.4 [4.0–4.7]	3.9 [3.6–4.2]
2	49 (102)	Yes	1.6 [1.3–1.9]	2.1 [1.8–2.5]	2.4 [2.1–2.6]
3	16 (33)	Yes	0.3 [−0.3 to 0.8]	3.3 [1.4–5.1]	5.4 [4.1–6.6]
4a	48 (100)	Yes	–	–	–
6	40 (83)	No	0.5 [0–0.1]	0.1 [0–0.1]	0.5 [0–0.1]
7	47 (98)	Yes	0 [–]	1.1 [0.9–1.4]	1.2 [0.8–1.6]
8	48 (100)	Yes	2.8 [2.0–6.3]	4 [3.8–4.2]	4.8 [4.5–5.1]
9	50 (104)	Yes	0.2 [0.1–0.3]	1.4 [1.2–1.5]	7.8 [7.7–8.1]
10	49 (102)	Yes	2 [1.8–2.3]	2.1 [1.9–2.4]	2.1 [1.8–2.3]
11	45 (94)	Yes	0 [–]	0 [–]	0 [0–0.1]
12	45 (94)	Yes	2 [2.0–2.1]	2 [1.9–2.1]	0.4 [0–0.1]
13	47 (98)	Yes	1.1 [0.9–1.3]	1.9 [1.7–2.1]	2.7 [2.4–3]
14	48 (100)	Yes	0.1 [−0.1 to 0.2]	0.1 [−0.1 to 0.2]	0.1 [−0.1 to 0.2]
15	52 (108)	Yes	0.2 [−0.1 to 0.6]	1.4 [1.3–1.6]	2.6 [2.4–2.8]
16	41 (85)	Yes	0.3 [0.1–0.5]	2.8 [2.4–3.2]	7.8 [7.6–8.1]
17	38 (79)	Yes	0.5 [0.3–0.6]	1.4 [1.2–1.6]	2.4 [2.2–2.5]

^aMissing data on NRS pain and NRS exertion.

NRS, numerical rating scale.

Table 4.

Changes in ABI, 30STS, 6MWT and ICQ from baseline to follow-up (n=16)

	Baseline	Follow-up	Change
Outcome	Mean (SD)	Mean (SD)	Mean [95% CI]
ABIa	0.6 (0.12)	0.71 (0.14)	0.11 [0.02–0.2]
30STSb	13.2 (2.8)	15.4 (3.2)	2.1 [1.2–3.1]
6MWTa	367.6 (59.8)	390 (73.1)	21.9 [6.9–36.9]
ICQ score	34.2 (13.3)	27.8 (20.5)	−6.3 [−11.9 to −0.8]c

^aMissing data on one patient.

^bMissing data on two patients.

^cICQ is scored 0=best. 100=worst, a negative number indicates an improvement.

30STS, 30 seconds sit-to-stand; 6MWT, 6-minute walk test; ABI, ankle-brachial index; ICQ, Intermittent Claudication Questionnaire.

Performance-based and self-reported function

The patients improved their ability to perform the 30STS by 2.1 repetitions [1.2–3.1], and the 6MWT was improved by 21.9 m [6.9–36.9]. The ICQ improved by −6.3 points [−11.9 to −0.8].

Discussion

The main finding of the present study was that 12 weeks of BFR-W was feasible in patients with IC. Fifteen of 16 patients completed all planned BFR-W sessions yielding an adherence of 93%. The adherence observed in the present study is similar to previous feasibility trials by Petersson et al. 38 and Høgsholt et al. 39, who investigated the feasibility of BFR training in elderly individuals and females with gluteal tendinopathy and reported a training adherence of 93 and 96%, respectively. However, the present findings may reflect the results of a selected group of patients highly motivated to improve their condition. Thus, the results may not necessarily be representative of the entire patient population. Additionally, no adverse events related to BFR-W were observed. This may be explained by the relatively low occlusion pressure at 60%, which may minimise the risk of adverse events, as suggested by Cerqueira et al. 31.

We found a significant improvement in ABI following the 12-week BFR-W intervention. This indicates that BFR-W is safe in patients with PAD and may even improve lower limb vascular function associated with improved walking function40,41. However, the improvement in ABI may also be explained by alterations or prescription of cholesterol-lowering medications such as statins42, which was not monitored in this study. Furthermore, changes in ABI may be reflective of inter-tester variability, which has been suggested to differ by 10%43.

The pain level reported before and after exercise in the present study was acceptable (NRS ≤5) in 98% of the sessions. This is likely to have positively affected adherence and completion rates in this study.

In addition to the findings on adherence and safety, an improvement in all secondary outcomes was observed. The mean improvement in the 30STS by 14% is, albeit slightly lower, in line with previous findings from Ozaki et al.17 (21% increase in 30STS) in elderly individuals following 10 weeks of BFR-W. Despite observing a significant change in the 6MWT of 21.9 m, this may not be considered a clinically relevant change. Sandberg et al.44 suggested the minimal detectable change in the 6MWT in patients with IC to be more than 46 m. Also, Gardner et al.45 found a change in the 6MWT of 45 m in patients with PAD following a 12-week at-home walking intervention three times a week with a mean session duration of 38.3 min. It is possible that the short duration per session (i.e. 10 min) and the low intensity employed in this study were insufficient to elicit clinically meaningful changes in the 6MWT. The mean rate of perceived exertion was estimated to be 2.8, which corresponds to moderate exertion46. The ICQ score improved by a mean of −6.3 points similar to the findings of Franz et al.47 reporting an improvement of −7.2 in patients with IC undergoing a supervised exercise programme.

Study limitations

The results of this study are restricted by some methodological limitations, primarily the small sample size leading to low statistical power. Although the improvements in ABI and functional capacity are encouraging, there was no control group, and therefore it was not possible to infer causation or to assess whether the patients achieved similar or better results from BFR-W compared with traditional walking training 9,10. However, since the primary aim of this study was to investigate the feasibility and safety of a BFR-W intervention in patients with IC, the above-mentioned limitations are considered acceptable.

Conclusion

BFR-W is feasible and appears to be safe in patients with IC in terms of completion rate, adherence to planned training sessions, number of adverse events and pain exacerbation. Improvements in performance-based and self-reported functioning (30STS, 6MWT, ICQ) were observed at follow-up. However, a future trial, with a larger sample size, investigating the effectiveness and safety of BFR-W compared to regular walking exercise is needed to clarify the clinical impact of BFR-W for patients with IC.

Ethical approval

Yes. Obtained from The Central Denmark Region Committees on Health Research Ethics (1-10-72-219-21).

Consent

Yes. All patients gave written informed consent prior to inclusion.

Sources of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of interest disclosure

There are no conflicts of interest.

Provenance and peer review

Not commissioned, externally peer-reviewed.